Laurédan Le Guen

Maxime Piton

Quentin Hénaut

Florian Huchet

Patrick Richard

Heat convection and radiation in flighted rotary kilns: A minimal model

Keywords: Heat transfer, Particle, rotary kiln, convection, radiation, granular materials

come

INTRODUCTION

In recent years, there has been a great deal of interest in the understanding of the behaviour of granular materials as they are used in a large number of engineering processes and present in many geophysical systems. Accordingly, many progresses have been made on the theoretical description of these systems and on the understanding of the physical mechanisms that govern their behaviour when they are exhibiting a gaseous, a liquid or a solid-like behavior. For instance, dilute granular flows are well described by a kinetic theory [1,2] and unidirectional dense flows properties are well captured by a Druker-Parger-like rheology [3] or by extensions of the aforementioned kinetic theory [4]. The behavior of such materials in the vicinity of jamming [5,6,7,8,9,10,11], close to destabilization [12,13] or submitted to aging processes [14,15,16,17] is also the subject of active current research. Heat transfer in such systems [18,19] and in particularly in gas-grains mixtures [20,21,22,23,24] is an important physical phenomenon which may govern a wide variety of natural systems (e.g. volcanic eruption) and industries (rotary kilns devoted to asphalt or cement production [24], torrefaction of biomass [25], fertilizers production, waste treatment, manufacturing of nuclear fuel [26]. . . ). This phenomenon is quite complex for several reasons [27]. Among them, we can mention that heat transfer may involve three different physical phenomena: (i) conduction (ii) convection and (iii) radiation. The case of conduction is also quite complicated by itself since it is influenced by the nature of the contacts between grains which is controlled by the nano-asperities present at the surface of the grains [17]. Recent and important progresses have been made in the numerical simulation of fluid interacting with moving particles using Discrete Element Methods (DEM) coupled to computational fluid dynamics (CFD) -see for example [22,28,29,30] or [20,31,32] for systems similar to ours-. However, their practical use to simulate industrial facilities is partially limited because they require important computational resources. Therefore, it is still necessary to develop physical models [33,34,35,36] capable to reproduce and predict the heat transfer between a gas and a granular medium. Here, we (i) present a minimal physical model which aims to quantify the heat transfer in the case of wall-bounded gas flow through dilute suspension of heavy grains and (ii) use this model to analyze the thermal efficiency of rotary kilns. In particular, we discuss the relative importance of radiation heat transfer with respect to convection and show that, the presented model captures the main experimental findings obtained in industrial facilities.

ROTARY KILN

Granular heat transfer modeling has a great importance in the material processing field. For example, rotary kilns are the most popular equipment dedicated to the drying, heating and coating of granular materials. A better understanding of the physical mechanisms [37,38,39] occurring within a rotary kiln is therefore crucial to optimize the industrial plants [40] in the context of sustainability, efficient energy use and reduction of toxic gases like polycyclic aromatic hydrocarbons. Here, we aim to model such a typical industrial equipment. A rotary kiln is a cylinder slightly tilted (a few degrees) with respect to the horizontal and which rotates around its axis (Figure 1). The material to be processed (typically grains) is fed into the upper end of the cylinder (the inlet). Due to gravity and the rotation of the kiln, the material gradually moves down towards the lower end (the outlet). In the case of grains, they are heated by a hot gas passing along the axis of the cylinder from the upper end to the lower end (co-current kiln) or from the lower end to the upper end (counter-current kiln). The hot gases are generally provided by an external furnace, or by a flame inside the kiln.

. ( 2017
)
In such a system, the grains are initially located at the bottom of the cylinder. However, Lshaped baffles (also called flights) located along the cylinder parallel to its axis on its inner diameter lift grains from the bed, bring them up to the top of the cylinder where they fall down due to gravity [41]. A granular curtain is thus created [41]. It ensures a proper mixing between grains and hot gases, and so enhances the heat exchange. It is thus convenient to consider that the physical system is made of four phases: (i) the gas, (ii) the dense granular bed, (iii) a dilute granular suspension i.e. a granular curtain and (iv) the walls bounding the system, and to study the heat exchange between those four phases.

Although the analysis presented in this work can be easily extended to the counter-current case, we will restrict ourselves to the co-current configuration. This choice may be surprising because it is reasonable to think that the maximum amount of heat transfer that can be obtained is more important with a counter-current kiln than with its co-current counterpart. Indeed, the former maintains a slowly declining temperature gradient whereas in the latter, the strong thermal difference at the inlet induces a higher initial gradient which falls off quickly, leading to potential heat loss. However, co-current rotary drum are still predominantly used in the industry for practical reasons: they are more easy to build, the fuel cost is nowadays not expensive enough to justify the replace old co-current kilns by new counter-current ones.

HEAT TRANSFER MODEL

In our study case, the rotary kiln is approximated by a drum where heat is exchanged between different phases that will be defined below. The drum is a cylinder made in stainless steel with an inner diameter, D D a length, L D and a thickness, d D . The convective hot gas flows from one boundary of the drum (the inlet) to the other (the outlet) along its axis. To simplify the problem we model the drum by two infinite and insulated horizontal walls separated by a distance D D (see Figure 2). This simplification neglects the action of rotation which is justified by the very small rotation speed used in industrial facilities. A gas is convected in parallel with those two walls and between the inlet of the system, defined by z = 0, and the outlet, defined by z = L D . A packing of grains (diameter d s , volumic mass density ρ s , thermal conductivity k s ) whose height is denoted by D b , is located on the lower wall. The whole is inclined with respect to the horizontal by a small angle θ (few degrees). We set the vertical origin at the level at the lower wall (x = 0). The upper wall is therefore located at x = D D . The action of the L-shaped baffles is implicitly taken into account by the presence of a uniform suspension (i.e. the volume

. ( 2017
)
fraction of the suspension depends neither on x nor on z) of the same type of grains which interact with the convected gas. In the granular suspension, the net transfer of thermal energy is potentially enhanced by an effective conduction from collisions between grains. However, in most practical cases the collision times between grains are too small to lead to a significant heat transfer between particles [42] and the volume fraction of the granular suspension is small enough to consider that the average number of collisions per grain is very weak. Moreover, we also assume that the grain size is large enough to neglect the velocity fluctuations of grains. In other words, the granular temperature and thus the self-diffusion of grains are negligible. Our model is therefore fundamentally different from that of Chen and Louge [21] and clearly not valid for highly agitated granular systems where the granular temperature is far from being negligible. It should be pointed out that such assumptions are justified by practical reasons. Our aim is not to derive a general and complex model that captures the behavior of a large variety of configurations but to focus on an applied point of view by deriving a minimal model devoted to thermal rotary kilns which are currently and widely used in the industry. Of course, we will also study the predictions and the limits of the aforementioned model. Another assumption consists in neglecting the momentum transfer between the gas and the grains. In other words the grains are too large and heavy to be influenced by the gas (Stokes number ≫ 1), and the granular suspension is dilute enough (< 10%) to neglect its influence on the gas. The only interaction between grains and gas is therefore related to the heat transfer. The motion of grains is induced by gravity through the inclination of the kiln and through the action of baffles, whose size is negligible compared to that of the drum. The former and the latter assumptions prevent the use of our work to model fluidized beds [22,43] of other systems where the grains are highly agitated and where fluid grains interactions govern significantly the dynamics. We also assume that the Biot number of grains B i = h(d s /2)/k s , where h is the heat transfer coefficient, is small with respect to 0.1. Thus, their internal temperature can be considered as uniform. Finally our last assumption is the following: for a given z-position along the axis of the drum, the grains belonging to the granular bed and to the granular suspension have the same temperature, T s . Therefore the heat transfer between grains of the suspension and those belonging to the bed is not considered. Such an assumption, which has been widely used previously in the literature [23,44] is an important simplification. Yet, in the case of a rotary kiln, the presence of baffles ensures the solid phase motion in order to renew the exchanges surfaces [45] and thus a reasonable homogeneity of the grain temperature. The relevancy of this simplification has been recently confirmed by numerical simulations coupling DEM with CFD [46] which reports, in a counter-current kiln, a reasonably weak variation of temperature of the solid phase (the maximal standard deviation is approximately 20 K for an average temperature of approximately 320 K). Moreover such an assumption is fully consistent with our aforementioned aim, that is, to derive the minimal model which can be used at the industrial scale. Our model is thus therefore a reasonable alternative to heavier approaches like numerical simulations coupling DEM and CFD. Thus, the grain temperature T s is assumed to be only a function of z. Similarly, the gas and the wall temperatures (respectively T g and T w ) are also assumed to depend only on z.

In such a system, several types of convective heat transfer should be taken into account:

• The convective heat transfer between the granular bed and the gas given by: h bg dS bg (T g -T s ), where h bg is the convective exchange coefficient between the granular bed and the gas, and dS bg , the differential surface area between the granular bed (or more precisely its free surface) and the gas. • The convective transfer between the gas and the granular suspension (i.e. the granular curtain): h cg dS cg (T g -T s ), where h cg and dS cg are respectively the convective exchange coefficient and the differential surface area between the granular suspension and the gas.

• The convective transfer between the granular bed and the contacting wall: h sw dS sw (T w -T s ). Similarly, h sw is the convective exchange coefficient and dS sw , the differential surface area between the granular bed and the inner contacting walls. • The convective transfer between the gas and the walls: h gw dS gw (T w -T g ) , where h gw is the gas-wall convective exchange coefficient and dS gw the corresponding differential surface area.

From the differential surfaces dS ij we can define length l ij by l ij = dS ij /dz where dz is the differential of z. The heat conduction between grains belonging to the granular bed is assumed to be negligible. It should be pointed out that, by assuming a constant grain diameter whereas real systems are polysized, we underestimate the heat exchange between the convected gas and the granular suspension. Yet, in view of industrial applications such an underestimation is better than an overestimation. The exchange surfaces between each phase are determined following the work of Piton et al. [47]. Using the same kiln geometry than ours and results from the literature, they provide expressions for the heat transfer coefficients which are empirical or semi-empirical. For the sake of clarity we also reported those expressions in tables I, II, III and IV. As we will show below, one of the key parameter is the fraction of grains in the granular suspension, α cg , i.e. the volume of the grains belonging to the suspension divided by the total volume of grains. The latter quantity is directly linked to the number of grains contained in the granular suspension per unit of length dN/dz through:

α cg = 2 3 dN dz d 3 s D 2 D F t , (1)
where F t is the ratio of the volume of grains to the volume of the drum, i.e. the kiln volume fraction. Then, the convective heat transfer coefficients are calculated from correlations available in the literature [47].

Thermal radiation is modeled using the following heat transfers:

• between the gas and the granular suspension:

dS cg E cg T 4 g -T 4
s , • between the gas and the free surface of the granular bed: dS bg E bg T 4 g -T 4 s , • between the gas and the wall of kiln: dS gw E gw T 4 w -T 4 g , • between the granular bed and the contacting wall of the kiln dS sw E sw T 4 w -T 4 s . In the latter expressions, the quantities E ij with i, j = {c, b, g, w} are the radiative heat transfer coefficients defined as E i,j = σε ij where σ is the Stefan-Boltzmann constant and ε ij the corresponding emissivity. The heat exchange surfaces dS ij are those used in the convective heat transfer.

So, at equilibrium, using the aforementioned types of heat transfer, the energy balances (i.e. the first law of thermodynamics) for the solid and gas phases as well as the insulated wall condition are respectively given by:

δ Qs = ṁs C p,s dT s = (h bg dS bg + h cg dS cg ) (T g -T s ) +E gs (dS bg + dS cg ) T 4 g -T 4 s +h sw dS sw (T w -T s ) +E sw (dS bg + dS cg ) T 4 w -T 4 s , (2)
δ Qg = ṁg C p,g dT g = (h bg dS bg + h cg dS cg ) (T s -T g ) +E gs (dS bg + dS cg ) T 4 s -T 4 g +h gw dS gw (T w -T g ) +E gw dS gw T 4 w -T 4 g , (3)
. ( 2017
)
and

h sw dS sw (T s -T w ) + E sw (dS bg + dS cg ) T 4 s -T 4 w +h gw dS gw (T g -T w ) + E gw dS gw T 4 g -T 4 w = 0. (4)
In the latter equations, δ Qi (with i = s, g respectively for the solid and the gas phase) is the heat transfer per unit time (the dot notation is used for the time derivative), ṁi the mass flow rate of the phase i, and C p,i the corresponding heat capacity. The set of Equations ( 2), ( 3) and (4) composes a system with the following boundary values: T s (0) = T s,0 and T g (0) = T g,0 are respectively the inlet temperature of solids (i.e. grains) and the inlet temperature of hot gases.

ANALYTICAL RESOLUTION IN THE CASE OF NEGLIGIBLE THERMAL RADIATION

The analytical resolution of previous model is not possible due to the presence of T 4 -terms. However, neglecting the heat transfer by radiation leads to a classical system of equations which can be solved analytically. The first law of thermodynamics applied to the grains and to the gas gives the respective heat flow rates :

ṁs C p,s dT s = h bg dS bg (T g -T s ) +h cg dS cg (T g -T s ) +h sw dS sw (T w -T s ) , (5) and ṁg
C p,g dT g = h bg dS bg (T s -T g ) +h cg dS cg (T s -T g ) +h gw dS gw (T w -T g ) . (6)
Since the system is insulated, the wall is in thermal equilibrium with the gas and the solid phase in such way that the energy balance is given by :

h sw dS sw (T w -T s ) + h gw dS gw (T w -T g ) = 0.
The latter equation leads to the identification of the inner wall temperature:

T w = h sw dS sw T s + h gw dS gw T g h sw dS sw + h gw dS gw . (7)
Combining Equations ( 5), ( 7) and ( 6) and using dS i,j = dz l i,j and Ψ ij = h ij l ij , with i, j = {c, g, w, b} we obtain the following first order differential system

d T g dz = - Ψ bg + Ψ cg + Ψ gw ṁg C p,g - Ψ 2 gw (Ψ sw + Ψ gw ) ṁg C p,g T g + Ψ gw + Ψ cg ṁg C p,g + Ψ gw Ψ sw (Ψ sw + Ψ gw ) ṁg C p,g T s , d T s dz = -I Ψ gw + Ψ cg + Ψ gw ṁg C p,g - Ψ 2 gw (Ψ sw + Ψ gw ) ṁg C p,g T s +I Ψ bg + Ψ cg ṁg C p,g + Ψ gw Ψ sw (Ψ sw + Ψ gw ) ṁg C p,g T g .
where I is a dimensionless number defined as ṁg C p,g / ṁs C p,s . After resolution, the latter system leads to:

     T g = T g,0 -T s,0 I + 1 exp (-z/Λ) + T g,0 I + T s,0 I + 1 , T s = -I T g,0 -T s,0 I + 1 exp (-z/Λ) + T g,0 I + T s,0 I + 1 . (8)
.

( 2017
)
In those solutions, Λ is a characteristic length defined as:

Λ = E I + 1 1 A + B + CD/(D + C) (9)
with A = h cg l cg , B = h bg l bg , C = h sw l sw , D = h gw l gw and E = ṁg C p,g , Thus, in the absence of thermal radiation the temperature profiles along the drum are given by exponential functions.

In the remainder of the paper, we will consider the following nominal case. Grains are spheres of diameter d s = 0.005 m and the curtain density is characterized by α cg = 3%. The solid mass flow rate is ṁs = 33.98 kg.s -1 . The gas is defined by its mass flow rate ṁg = 3.74 kg.s -1 (unless otherwise specified), its density ρ g = 0.84 kg.m -3 and its viscosity µ g = 3.59 10 -5 Pa.s -1 . For the sake of simplicity, we do not take into account the variations of the two latter quantities with the temperature. However, in our model, they only influence h cg and h gw through the Reynolds number. Yet, in presence of radiation, the variations of µ g and ρ g are really important only when radiation is negligible, i.e. for a gas temperature below 600K. Within this range temperature, the effect on the heat transfer coefficients is negligible. The convective heat transfer coefficients corresponding to the nominal case are given by the following values (see [47]):

h bg = 102.83 W.m -2 .K -1 , h cg = 112.80 W.m -2 .K -1 , h gw = 35.23 W.m -2 .K -1 and h sw = 242.96 W.m -2 .K -1 .
Note that, those values are obtained by semi-empirical relations (see tables I, II, III and IV) obtained from the study of industrial rotary kilns used to process various types of granular matter [47] and that the heat transfer coefficients depend on both α cg and ṁg . Although we focus here on the case of asphalt plants, our approach is valid for any type of granular material as long as the assumption of the model are valid. It should be the case, for example, for kilns used to dry fertilizers. For the nominal case, the exchange lengths, which depend on the grain distribution in the kiln cross-section (see table V and [47]), are given by l bg = 2.320 m, l cg = 9.71 m, l gw = 3.55 m and l sw = 1.79 m. Those values depend on α cg and will also be modified accordingly when the effect of that parameter will be studied.

Table I. The coefficient h bg depends on Ag (the cross section of "hot gas" phase) and ṁg (the mass flow rate of hot gases in the kiln). The constants H bg , σ bg and η bg are respectively equal to 0.4 W.m -2 .K -1 , 3600 kg -1 .m 2 .s and 0.62.

Convective transfer between the gas and the granular bed

Coefficient

h bg = H bg (σ bg ṁg /A g ) η bg Validity range h bg ∈ [50, 100] W.m -2 K -1 [48]

Sketch

Regarding the heat transfer capacities we will use C p,s = 830 J.kg -1 .K -1 and C p,g = 1100 J.kg -1 .K -1 which also correspond, as mentioned above, to the asphalt plant case.

Figure 3 reports variations of the temperatures versus z for several values of α cg . The model predicts that the temperature reached at equilibrium (for z tends towards +∞) is the average of

. ( 2017
)
Table II. The coefficient hcg depends on ks, the thermal conductivity of solids, ds the grain size, Pr the Prandtl number i.e. the ratio of kinematic viscosity to the thermal diffusivity and the particle Reynolds number Rep defined as vgds/νg, where vg and νg are respectively the gas velocity and the gas kinematic viscosity. The coefficients Acg, Bcg, a, b and c depend on the range of the particle Reynolds number Rep [49].

Convective transfer between the gas and the granular suspension

Coefficient

h cg = k s d s 2 + A cg R a e,

Convective transfer between the gas and the walls

Coefficient

h gw = k g D h (A gw R e ηgw + B gw R e,ω
ηω,gw ) with

D h = D t 2π -ε B + sin ε B 2π -ε B -sin ε B
Validity range 1100 < R e,ω < 58000 and 0 < R e < 30000 [50] Sketch the gas and grain inlet temperatures weighted by the corresponding heat flow rates. Note that this equilibrium temperature does not depend on the exchange surfaces. The latter quantities have only an influence on the dynamics and, obviously, the distance necessary to reach the equilibrium temperature are smaller for larger exchange surfaces. This result can be obtained by a simple application of the first law of thermodynamics.

In order to simplify our analysis, it is reasonable to consider a kiln with a good efficiency,

. ( 2017
)
Table IV. The coefficient hsw depends on ks the thermal conductivity of solids D D the kiln diameter, ε B , ω and as, the thermal diffusivity of the solid phase, i.e. ks/(ρs Cp,s). The constants Ksw and ηsw are respectively equal to 11.6 and 0.3

Convective transfer between the granular bed and the walls

Coefficient

h sw = k s ε B D D K sw 2ε B D 2 D ω 2 a s ηsw Validity range ω ∈ [3.5, 10] rad.s -1 [51] Sketch Table V.
The lengths lpw, lsp, lcg and l bg depend on the number of baffles, n F , the kiln diameter D D and on the angle of the bed in the kiln ε B (see [47]) which is determined using α B F t = (ε B -sin ε B cos ε B )/π where α B is the fraction of grain in the bed and F t the kiln volume fraction. i.e. a kiln for which the thermal transfers with the walls are much lower than those between the gas and the grains. This assumption is fully valid for kilns having baffles which ensure a good heat transfer between the grains and the gas. In such a case, which corresponds to recent experimental measurements [52], the term corresponding to the thermal exchange with the walls (C D/(C + D)) in Equation ( 9) is between 2 and 30 times smaller than those corresponding to the transfer between the gas and the grains (A and B) and the characteristic length can be reduced to the following:

l gw D D πε B l bw D D ε B l cg n F 3π ρ b ρs D 2 D 2dp F t α cg l bg D D sin ε B
Λ app ≈ E (I + 1)(A + B) = κ h cg l cg + h bg l bg , ( 10
)
where κ is the effective mass flow rate κ = ṁg C p,g ṁs C p,s /( ṁg C p,g + ṁs C p,s ). 10) in the case of efficient kilns. Note that the approximation is especially good for large values of α cg i.e. for an important heat transfer between the granular suspension and the gas (with respect to heat transfer with the walls) and thus for small values of Λ.

Obviously, and in agreement with Figure 3, increasing α cg and thus the surface exchanges leads to a decrease of the characteristic length of the temperature variation along the drum. However, one should keep in mind that the present model is only valid for dilute granular suspensions, i.e. low values of α cg . Otherwise, the momentum exchange between the gas and the grains cannot be neglected. The characteristic length Λ thus depends on the gas and solid flow rates, ṁg and ṁs . If one of the flow rates is increased while keeping the other flow rate and all the other parameters constant, κ and consequently Λ increase. Thus a longer drum is required to reach the same equilibrium temperatures. Such a result can be understood easily. For example, if ṁs is increased while the other parameters are kept constant, the amount of heat transferred from the hot gas is shared by a larger number of grains, thus their temperature at the outlet of the

. ( 2017
)
drum is lower. The effect of both α cg and ṁg is highlighted on Figure 5 where we have reported the evolution of the characteristic length Λ versus those two parameters. As expected, Λ decreases with (i) increasing α cg and (ii) decreasing ṁg . Thus, the smaller characteristic lengths are obtained for important values of α cg and small values of ṁg . Note however, that the effect of ṁs , contrary to that of ṁg , might be more complex since its modification might also induce a variation of α cg and thus of the exchange lengths. To fully understand the effect of ṁs on Λ, an investigation of variety of parameters (velocity of the drum, number of grains present in the baffles. . . ) which depend on the details of the kiln geometry is required. Such a study is beyond the scope of this paper.

QUANTIFYING THE IMPORTANCE OF THERMAL RADIATION

In previous analytical solution of the model, we have neglected thermal radiation. However, it is possible to numerically solve the full model (including thermal radiation, see Equations ( 2) and ( 3)) following the work of Piton et al. [47]. Figure 6 reports the numerical results obtained for α cg = 3%. Note that, as expected, the heat supplied to the system at its outlet is the same with and without radiation as long as the length of the drum is large enough to reach the equilibrium temperature. Indeed, since the system is insulated the temperatures at the equilibrium, i.e.

T g (∞) = T g,∞ , T s (∞) = T s,∞ and T w (∞) = T w,∞
, are also the same, independently of the fact that radiation is taken -or not-into account.

As mentioned above, the general equations which include thermal radiation terms cannot be solved analytically due to the T 4 -terms. In such a case, to define a characteristic length of the phenomena and thus obtain an efficiency criterion it is necessary to fit the numerical results by an adequate function. The z-profiles of the temperatures obtained numerically cannot be fitted by an exponential function whose variation is too rapid. Thus, following what is classically done in such a case, we try to fit our results by a stretched exponential given by Equation ( 11) and obtained satisfactory results. First used by Kohlrausch in 1854 [53] to describe mechanical creep, this expression was far later popularized by Williams and Watts [54] who described dielectric relaxation in polymer as being stretched exponential functions. It is now frequently applied to a large range of relaxations in disordered thermal systems as glasses or granular materials [55,56] and is often called the KWW law. Its expression is given by:

T γ (z) = T γ,∞ + (T γ,0 -T γ,∞ ) exp -(z/λ γ ) βγ , (11)
. ( 2017) where index γ stands for the studied phase (i.e. solid, gas or wall). Note that the stretched exponential is also known as the complementary cumulative Weibull distribution. To explain the use of such a fit function, one can consider a small region around of the drum z = z i for which the radiative

E ij l ij (T 4 g -T 4 s ) can be approximated by E ij l ij (T g -T s )(T g,i + T s,i )(T 2 g,i + T 2 s,i )
where T g,i and T s,i are respectively the solid and gas temperature at z = z i . This assumption leads to a linear system of differential equations around z i . The solution drives exponential functions whose characteristic length depends on T g,i and T s,i and increases with z i . The full solution may thus be seen as a combination of simple exponential decays which is known as a stretched exponential function.

As mentioned above the temperatures reached for z → +∞ are the same with and without radiation : T g,∞ = T s,∞ = (T g,0 I + T s,0 )/(I + 1). The expressions of the gas and solid temperatures can thus be respectively written as :

       T g = Tg,0-Ts,0 I+1 exp -(z/λ g ) βg + Tg,0I+Ts,0 I+1 , T s = -I Tg,0-Ts,0 I+1 exp -(z/λ s ) βs + Tg,0I+Ts,0 I+1 . (12)
It should be pointed out that, for the solid phase, the stretched exponential fit is not able to reproduce correctly the data close the equilibrium value of the temperature. This is potentially problematic for very long drum and/or very low values of α cg (i.e. α cg ≤ 0.1%). However, close to the inlet of the kiln, the fit is fully valid. The two free parameters used for the fit are λ γ , the characteristic length of the stretched exponential and β γ , its power. Interestingly, our numerical results show that the dependence of the phase is very weak, i.e. β s ≈ β g ≈ β w = β and λ s ≈ λ g ≈ λ w = λ are reasonable approximations as long as we restrict ourselves to the region of the kiln for which the stretched exponential fit is valid. Therefore the profiles of the temperatures within the system are determined by the two parameters of the stretched exponential which depend on α cg and ṁg (see Figure 7). Two important remarks should be made. Firstly, both λ and β increase with the gas flow rate ṁg . This result indicates that increasing the mass flow rate of the gas requires to use longer kilns to reach equilibrium. Secondly, an increase of α cg leads to a decrease of the exponent of the stretched exponential and of the characteristic length. The latter result is expected since an increase of α cg increases the surface exchange between the granular suspension and the gas and thus improves the heat exchange between the gas and the grains. Note that the relation between the two parameters β and λ is not one-to-one. In other words one cannot deduce one of the parameters from the knowledge of the other. However, an interesting result should be pointed out: the relation between the two parameters λ and β are one-to-one for each value of α cg , i.e., the two parameters β and λ are correlated if α cg is kept constant. Interestingly, the correlation is linear (see Figure 8c) but, to date, we have no explanation for this linearity which warrants further studies. Our analysis raises another question: is the characteristic length in presence of radiation, (i.e. λ) linked to that obtained in absence of radiation, (i.e. Λ)? Figure 8b reports the evolution of the former quantity versus the latter. Clearly and surprisingly, they are linearly correlated for each value of α cg . Naturally, β and λ being correlated for each value of α cg , β is also linked to Λ, the characteristic length in absence of radiation (Figure 8c). The origin of those linear correlations is not established.

. ( 2017
)
In our system, the gas temperatures range from a few hundreds of Kelvins to a few thousands, bringing us to the question of whether radiation should be neglected (i.e. for low temperatures) or not (i.e. for high temperatures). Thus, we compare the temperatures obtained with the analytical solution of the model without radiation to those obtained by the numerical resolution of the full model. Figure 9a reports the numerical (i.e. with radiation) and analytical (i.e. without radiation) temperature profiles for a fraction of grains belonging to the granular suspension α cg = 3%. As expected, the influence of the radiation is significant especially at the early stages of the heating, i.e. when the gas temperature T g , and thus T 4 g , are important. Similarly, the influence of the radiation becomes smaller when the gas temperature .

(2017) T g decreases. Radiation might therefore be neglected only at lower temperature values. To illustrate this purpose, we show in Figure 9b the analytical and numerical relative variations of T g (i.e. the quantity (T g -T g,∞ )/T g,0 ) for α cg = 3% and for several initial temperatures (see caption). As an example, for α cg = 3% and T g,0 = 798 K the maximum relative error is found to be around 4%.

The validity of our model is then tested by fitting experimental measurements of the gas temperature data obtained experimentally in an industrial flight rotary kiln devoted to the asphalt materials manufacturing [40] by simple exponential functions (Figure 10). The characteristic length obtained is close to that obtained by Equation ( 9) (roughly 10% difference). The grain and wall temperatures are also well reproduced by simple exponentials for which the characteristic lengths and the equilibrium temperatures are set to the values obtained with the fit of the gas temperature. It should be pointed out that stretched exponentials also fit correctly experimental data, without being significantly better. Unfortunately, the number of experimental measurements is too small to differentiate the two fits.

DISCUSSION: OPTIMAL LENGTH OF THE KILN

The above study predicts the spatial evolution of the grain temperature within a model kiln with or without radiation. It is thus possible to estimate the optimal length of a rotating kiln allowing the grains to reach a given temperature, T ν . In the present case, calculation of the requested temperature, T ν , is obtained for a given length L ν , in such way that T ν = T s (z = L ν ). Of course, for a given grain flow rate, the gas flow rate or the initial temperatures have to be chosen in order that the equilibrium temperature T s,∞ = (T g,0 I + T s,0 ) / (I + 1) is larger or equal to T ν . Otherwise, T ν is unreachable. If T ν can be reached, the simplest solution consists in using a very long kiln to be sure that the outlet temperature of the grains is equal to or larger than T ν . However, a too long drum is not efficient since energy is used to increase the grain temperature up to an unnecessarily high value. A criterion is therefore necessary to quantify the efficiency of the kiln relative to its length. From the above analytical resolution (i.e. without radiation) our empirical expressions (i.e. with radiation) of T g , the length L ν at which the grain temperature reaches T ν can be easily obtained. If the length of the kiln L D is lower than L ν , the requested temperature cannot be reached. The efficiency can be therefore defined as the following ratio:

ε = LD 0 T s (z) dz Lν 0 T s (z) dz if L D < L ν . (13)
In such a case, the efficiency increases from zero when the length of the drum is increased and reaches its maximal value (ε = 1) when the length of the drum is equal to L ν . The criterion can be seen as the ratio of the energy used to set the grain temperature to its value at the outlet of the drum over the energy necessary to achieve the requested temperature. For a drum whose length is larger than L ν , the temperature of the grains at the outlet of the device is larger that the requested temperature. Thus the final temperature of the grains is higher than the requested temperature and part of the used energy is wasted. Therefore, the efficiency of the process decreases with drum's length. It can be defined as:

ε = 1 - LD Lν T s (z) dz LD 0 T s (z) dz if L D > L ν . (14)
In the latter equation, the ratio of the two integrals can be seen as the ratio of the wasted energy over the total energy. The definition of our efficiency criterion is sketched in Figure 11a and an example of the dependence on the efficiency with the length of the drum is given on Figure 11b. Note that radiation, by increasing heat exchange between the gas and the granular suspension, improves the efficiency of the kiln for a given z-position. However, the shape of the curve is not significantly influenced by the presence (or the absence of) radiation as long the length of the kiln is made dimensionless by L ν . Such kind of approach can also be applied to existent kilns, i.e. kilns for which L D is fixed. In this case, the gas temperature at the inlet can be chosen to obtain the requested solid temperature at the outlet (Equations ( 8) or (12)). Yet, if for practical reasons, it is not possible to set the inlet temperature at its optimal value, the efficiency can be determined using Equations ( 13) and (14) in which L ν is the length corresponding to the requested temperature. The requested temperature for the grains is Tν and the length at which that temperature is reached is Lν . This temperature must be lower than the equilibrium temperature reached for an infinite drum otherwise it is unreachable for any length. If the size of the drum L D is lower to Lν (blue or light grey drum), the temperature Ts,ν cannot be reached. The efficiency ε increases towards 1 when L D tends towards Lν which corresponds to the ideal length of the drum (green or medium grey drum). On the contrary if L D > Lν (red or dark grey drum) the grain temperature at the outlet is greater than Ts,ν , leading to a waste of energy. (b) The efficiency of the kiln depends on the drum's length. The present curve has been obtained using Equation (11) with β = 0.76 and λ/Lν = 0.47. Efficiency rises to reach its maximum value at L D = Lv. Above Lv, the energy waste increases and the efficiency decreases progressively. The inset reports the same data in a lin-log scale.

CONCLUSION

In this paper, we report a theoretical approach aiming to model heat transfer between a convective gas and a model granular system. The studied system is typical of a rotary kiln commonly used in industry to dry grains (asphalt production, fertilizers production, waste treatment. . . ) i.e. a dilute suspension of heavy grains interacting with a convected gas only through heat exchange. We divided the system into different "phases" (gas, granular suspension, granular bed, walls) which interact through exchange surfaces. The granular phases are treated as effective continuous media. The model is solved analytically in the absence of radiation and it is shown that the temperature profiles along the drum are governed by one characteristic length whose expression depends on the heat transfer properties and on the exchange surfaces. In the presence of radiation, the profiles of the temperatures along the axis of the drum are well fitted by stretched exponentials whose parameters depend on the surface exchanges but are the same for each phase of the system. As expected, the presence of radiation does not modify the equilibrium temperature but reduces the length required to reach equilibrium. Finally a criterion quantifying the efficiency of the process is proposed. It is based on an estimation of the optimal length of the kiln as a function of the temperature of the grains at the outlet of the kiln. Similar analysis should be applied to the counter current case in order to obtain rigorous energetic diagnostics of different rotary kiln systems. It should be pointed out that several assumptions have been made to derive the present model. Although they may appear to be somewhat crude, they are justified in the case of a convected gas moving through dilute suspension of heavy grains, which corresponds to the majority of application in the field of civil engineering. However, the large variety of granular materials present in other industrial fields deserves consideration of a more detailed model which should take into account a diffusional time within the grain for larger Biot number and agitation of grains within the suspension (i.e. granular temperature). Note also that, although in the case of kiln devoted to asphalt production the moisture of the grains evaporates quickly and in vicinity of the outlet, it should probably be considered for other types of kilns (e.g. kilns devoted to fertilizer production).

Our simple model can be used in industry to help the design of efficient kilns. Indeed it gives an efficiency criterion which estimates the optimal kiln length, i.e. the length of the kiln which allows to reach a given final temperature. Thus it helps the design kilns which are really adapted to the intended application.

Figure 1 .

 1 Figure 1. Sketch of a typical rotary kiln. The heat is provided by a direct fire natural burner. Shape metal slats called blades or flights are attached to the interior surface of the kiln. They lift particles located at the bottom of the kiln to the gas. The kiln is inclined (a few degrees) with respect to the horizontal.

Figure 2 .

 2 Figure 2. Sketch of the system. Two horizontal walls are separated by a distance D D . A hot gas flows in the system in parallel with the walls. A granular bed (height D b ) rests at the lower wall. L-shaped baffles (not shown) lift grains from the granular bed to the upper wall leading to an homogeneous suspension of grains which falls down due to gravity. The whole is inclined at an angle θ with respect to the horizontal, leading to a global motion of the grains along the drum's axis.

  p + B cg R b e,p P c r Validity range if R e,p < 200, A cg = 0, a = 0, B cg = 0.6, b = 1/3 and c = 1/3 if 200 < R e,p < 1500, A cg = 0.5, a = 0, B cg = 0.02, b = 0.8 and c = 1/3 if R e,p > 1500, A cg = 4.5 × 10 -5 ; a = 1.8; B cg = 0, c = 0, d = 0 Sketch Table III. The coefficient hgw depends on kg, the thermal conductivity of gas, Re the Reynolds number Re = D D vg/νg, on the rotational Reynolds number Re,ω = D 2 D ω/2νg (ω is the angular velocity of the kiln) and on D h an effective diameter. The latter quantity is determined from D D and ε B , the angle whose sinus is equal to the ratio 2δ/D D , where δ is the distance between the center of the kiln and the free surface of the granular bed (see the two last sketches of the table). The constants Agw, ηgw, Bgw and ηω,gw are respectively equal to 0.02, 0.93, 8.5 × 10 -6 and 1.45.

Figure 3 .

 3 Figure 3. Profiles of the gas (a), wall (b) and grain (c) temperatures versus the position z along the drum axis depend on the density of grains within the granular suspension. The curves reported have been obtained for αcg = 1%, 2%, 3%, 4%, 5% and 6%. The arrows indicate increasing αcg.

Figure 4 .

 4 Figure 4. The approximated characteristic length Λapp [Equation(10)] is found to be very close to the exact value Λ [Equation (9)] demonstrating the relevancy of the latter approximation for wellinsulated kilns. The points correspond to simulations obtained with αcg = 1%, 2%, 3%, 4%, 5% and 6% and ṁg = 1.1, 1.66, 2.06, 2.56, 3.12, 3.74 and 3.90 kg.s -1 . The lengths are made dimensionless by Λmax, the maximal value of Λ. The dashed line corresponds to Λapp/Λmax = Λ/Λmax.

Figure 4

 4 Figure4reports the evolution of the characteristic length determined by neglecting the heat transfer with walls Λ app [Equation(10)] versus its full expression [Equation (9)]. As expected both quantities are close to each other (less that 15% of difference) showing the relevancy of Equation(10) in the case of efficient kilns. Note that the approximation is especially good for large values of α cg i.e. for an important heat transfer between the granular suspension and the gas (with respect to heat transfer with the walls) and thus for small values of Λ.

Figure 5 .

 5 Figure 5. When radiation is not taken into account, the evolution of the temperatures along the kiln are given by exponential functions whose characteristic length varies with αcg and ṁg.

Figure 6 .

 6 Figure 6. Profiles of the gas (Tg), wall (Tw) and grain (Ts) temperatures versus the position along the drum axis in the presence of radiation radiation (symbols). The initial gas and solid temperatures are respectively equal to 1873 K and 298.15 K. The curves have been obtained using αcg = 3%. The dashed lines correspond to the fits obtained using stretched exponentials [Equation (11 )].

Figure 7 .

 7 Figure 7. When radiation is taken into account, the temperatures are well fitted by stretched exponential functions whose parameters (the characteristic length λ (a) and the power β (b)) are both found to be independent of the phase but vary with ṁg and αcg.

Figure 8 .

 8 Figure 8. In presence of radiation, the characteristic length obtained by fitting the temperature evolution, λ and its power β are linked linearly for each value of αcg, the fraction of grains in the granular suspension (a). Similarly, for each value αcg, the same characteristic length is also linked linearly to Λ the characteristic length in absence of radiation (b). Consequently the power β is also linearly linked to λ, for each value of αcg. The arrows indicate increasing ṁg.

Figure 9 .

 9 Figure 9. (a) Profiles of the gas (Tg), wall (Tw) and grain (Ts) temperatures versus the position along the drum axis with (numerical) and without (analytical) radiation. The initial gas and solid temperatures are respectively equal to 1873 K and 298.15 K. The curves have been obtained using αcg = 3%. As expected the variations are more important with radiation and, at thermal equilibrium, all the temperatures are identical. (b) Relative difference between the numerical and analytical temperatures along the drum axis at different initial gas conditions for αcg = 3%. At the inlet, the grain temperature is fixed to 298.15 K. The curves have been obtained for 398.15 K, 598.15 K, 698.15 K, 798.15 K, 998.15 K, 1198.15 K, 1398.15 K, 1598.15 K, and 1898.15 K. The red arrow indicates increasing T g,0 .

Figure 10 .

 10 Figure 10. The temperatures obtained experimentally in an industrial rotary kiln devoted to asphalt production [40] (symbols) are well fitted by simple exponentials sharing the same characteristic length and equilibrium temperature. The rate of the production is 140 Tons per hour.

Figure 11 .

 11 Figure 11. (color online) (a) Efficiency criteria. The requested temperature for the grains is Tν and the length at which that temperature is reached is Lν . This temperature must be lower than the equilibrium temperature reached for an infinite drum otherwise it is unreachable for any length. If the size of the drum L D is lower to Lν (blue or light grey drum), the temperature Ts,ν cannot be reached. The efficiency ε increases towards 1 when L D tends towards Lν which corresponds to the ideal length of the drum (green or medium grey drum). On the contrary if L D > Lν (red or dark grey drum) the grain temperature at the outlet is greater than Ts,ν , leading to a waste of energy. (b) The efficiency of the kiln depends on the drum's length. The present curve has been obtained using Equation(11) with β = 0.76 and λ/Lν = 0.47. Efficiency rises to reach its maximum value at L D = Lv. Above Lv, the energy waste increases and the efficiency decreases progressively. The inset reports the same data in a lin-log scale.

ACKNOWLEDGMENTS

We thank Bogdan Cazacliu, Yannick Descantes, Nicolas Roquet, Riccardo Artoni and Erwan Hamard for fruitful discussions and Jean-Marc Paul for technical assistance. We are indebted to Andrew Hobbs for a critical reading of the manuscript and for kindly providing us with unpublished numerical results.


Chêne Geneviève
email: genevieve.chene@isped.u-bordeaux2.fr

Phillips Andrew

Costagliola Dominique

Sterne Ac

Furrer Hansjakob

Del Amo

Mocroft Amanda

Monforte Antonella D'arminio

Miro Dabis François

MD Geneviève ; Chêne

Andrew Phillips

Dominique Costagliola

Jonathan A C Sterne

Hansjakob Furrer

Julia Del Amo

Amanda Mocroft

Antonella D'

Arminio Monforte

François Dabis

José M Miro

Diana Barger

Monique Termote

Christine Schwimmer

Rikke Salbøl Brandt

Nina Friis-Moller

Dorthe Raben

David Haerry

Matthias Egger

Ian Weller

Stéphane De Wit

Cohort Profile: Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord

Keywords: HIV, AIDS, cohort collaboration, prognosis, observational epidemiology

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

• Non-injection drug users living with HIV with CD4 cell counts above 500/mm 3 after starting cART had mortality patterns similar to those in the general population.

• COHERE has informed models of HIV progression and the effect of therapy which have been used to characterize HIV-infected populations, inform public health policy and serve as a basis for cost-effectiveness analysis. Widespread access to effective combination antiretroviral therapy (cART), beginning in 1996, dramatically reduced the number of AIDS-related events and deaths in people living with HIV (PLWH) in high-income settings. [START_REF] Mocroft | Decline in the AIDS and death rates in the EuroSIDA study: an observational study[END_REF] The study of prognosis and specific clinical outcomes therefore requires larger populations. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) was founded in 2005 to continue to advance epidemiological research on the prognosis of PLWH in Europe. COHERE has expanded and strengthened collaborative efforts in Europe and facilitated those with other regions by ensuring that longitudinal data, the product of early investments in clinic-based databases and observational studies, were compiled and harmonized. In 2011, COHERE joined three other European HIV collaborations, PENTA, EuroSIDA, and CASCADE to form "EuroCoord", a Network of Excellence funded by the European Commission Seventh Framework Programme. [START_REF]EuroCoord : Enhancing clinical and epidemiological HIV research in Europe through cohort collaborations[END_REF] COHERE also collaborates with the ART Cohort Collaboration (ART-CC) and the International Epidemiologic Databases to Evaluate AIDS (IeDEA) global network. [START_REF] May | Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)[END_REF][START_REF] Egger | Cohort Profile: the international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa[END_REF] How does COHERE operate? COHERE operates according to the principles set out in Box 1. Projects in COHERE provide added value by only addressing scientific questions that cannot be answered by participating cohorts. Executive Committee (EC). The EC --composed of three representatives from each of the two regions, and the two RCC Heads --acts as the functional link between the RCCs and the SC. COHERE projects are organized by "themes" (Prognosis and the effect of antiretroviral therapy (ART), Hepatitis, Opportunistic Infections, Malignancies, Late Presentation, and Socio-economic Inequalities) to encourage collaboration and streamline the project proposal process. Theme Leads stimulate scientific enquiry within their theme and develop projects. A detailed account of how COHERE operates is described in the Manual of Operations (www.cohere.org).

Who participates in COHERE?

COHERE has grown from 33 cohorts in 2005 to 40 in 2015. COHERE initially approached cohorts because of their proven ability to address scientific questions and collect good quality data at clinical sites. As COHERE is a project-based collaboration, the data pooled in annual mergers depend on the projects included. Western European countries with longstanding national cohorts contribute a large proportion of person-years of follow-up, but there is an increasing number of individuals in care in Eastern Europe, primarily via the EuroSIDA network. 5 30, 43]. The primary mode of HIV transmission is sexual contact [homosexual/bisexual contact (38.7%), heterosexual contact (37%)], followed by injection drug use (IDU) (13.5%). Overall, 71.6% of the sample has never had a clinical AIDS diagnosis before or during enrolment. The median CD4 cell count at enrolment, defined as the period six months prior to and one month after enrolment date, was 340 cells/mm 3 [IQR: 170, 530] in adults (Table 2a). Of those with an available CD4 cell counts at enrolment, 29% had <200 cells/mm 3 , 22% had between 200 and 350 cells/mm 3 , and 49% had >350 cells/mm 3 . Of those younger than age 13 (N=2808, representing 23 458), 93.7% were infected via vertical transmission and 73.4% had never had an AIDS diagnosis (Table 2b).

How often have they been followed up?

As a consortium of cohorts comprising clinic and interval cohorts, patient follow-up varies.

For clinic or hospital-based cohorts, average patient follow-up reflects current standards of care in those countries.

A derived measure of lost to follow-up (LTFU) was constructed by estimating the median last clinical encounter (defined as either visit and/or the date of last laboratory test) per active cohort. Those individuals who had not had a clinical encounter in the 18-months prior to this date were considered to be LTFU. Those who died during the same period were excluded. [START_REF] Kjaer | HIV cohort collaborations: proposal for harmonization of data exchange[END_REF] For approved projects, COHERE DMs organize data collection by developing a standardized operating procedure (SOP) for individual cohort DMs. Data are submitted in two stages via the HIV-Distributed Data Management (HIV-DDM) Tool. [START_REF]HIV-Distributed Data Management[END_REF] This implies that data submissions must therefore pass all format and edit checks, defined in HICDEP, before the submission can be completed. Additional inconsistencies are identified centrally. Cohorts are given an 8week window to address said data inconsistencies before completing the second and final submission. Once data are merged, likely duplicate patient records between and within cohorts are identified using probability linkage. Data

What has been found?

Projects within the COHERE collaboration have led to the publication of 28 articles in peerreviewed journals as of April, 2016, contributing high-quality evidence that has informed clinical and public health decision-making.

Prognosis and the effect of ART

The "Prognosis and the effect of ART" group focuses on clinical outcomes in patients treated with cART. The effect of age on the response to cART was studied in around 50,000 antiretroviral-naive individuals. Older individuals were characterized by low pre-ART CD4 cell counts, and experienced poorer immunological responses but better virologic responses, indicating those who are diagnosed or treated late are at increased risk of clinical events. [START_REF] Sabin | Response to combination antiretroviral therapy: variation by age[END_REF] Non-IDU HIV-infected individuals who achieved high CD4 cell counts after starting cART were found to have mortality patterns similar to those in the general population. Mortality was found to be persistently higher in individuals with a prior AIDS diagnosis [START_REF] Lewden | All-cause mortality in treated HIV-infected adults with CD4 >/=500/mm3 compared with the general population: evidence from a large European observational cohort collaboration[END_REF] , while the incidence of AIDS events continued to decline until CD4 cell counts were greater than 750 cells/mm 3 . [START_REF] Mocroft | The incidence of AIDS-defining illnesses at a current CD4 count >/= 200 cells/muL in the post-combination antiretroviral therapy era[END_REF] In patients with viral suppression, the risk of a new AIDS events or death followed a CD4 cell count gradient, even benefiting those with a CD4 cell count ≥500 cells/mm 3 . 11 Individuals who were virally suppressed on cART for more than three years but had incomplete CD4 cell recovery experienced substantially higher rates of mortality from both AIDS and non-AIDS causes, suggesting that these individuals should be monitored for diseases not conventionally considered HIV-related, especially non-AIDS defining cancers Fewer than 9% of adult patients had experienced TCVF at year nine after starting cART. [START_REF] Lodwick | Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years[END_REF] The risk of TCVF was somewhat higher in children and particularly higher in adolescents. [START_REF] Castro | Risk of triple-class virological failure in children with HIV: a retrospective cohort study[END_REF] Virologic suppression after TCVF was found to have increased from 20% in 2000 to 58% in 2009. Rates of AIDS and death also declined over time in people with TCVF. [START_REF] Castagliola | Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study[END_REF] The incidence of TCVF in people on cART declined after 2008, and prevalence stabilized at around 2.5%. [START_REF] Nakagawa | Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe[END_REF] An approximately linear inverse relationship between log 10 viral load and CD4 cell count in people with TCVF points to likely immunologic benefits of reducing viral load, even by modest amounts, without necessarily resulting in an undetectable viral load. 17

Late Presentation

Late presentation is defined as an HIV-diagnosis with a CD4 cell count <350/mm [START_REF] May | Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)[END_REF] [START_REF] Mocroft | Continued late presentation for HIV care across Europe[END_REF] These findings have provided comprehensive evidence of patterns in late presentation in Europe and have informed discussions around earlier and more widespread testing for HIV and linkage to HIV care. [START_REF] Pharris | Ten years after Dublin: principal trends in HIV surveillance in the EU/EEA, 2004 to 2013[END_REF]

Opportunistic Infections

Thirty per cent of HIV infected people either present late with an OI or are at significant risk of an OI. [START_REF] Mocroft | Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)[END_REF] The COHERE OI group has described both the spectrum and incidence of OIs in patients on cART with high CD4 cell counts. [START_REF] Mocroft | The incidence of AIDS-defining illnesses at a current CD4 count >/= 200 cells/muL in the post-combination antiretroviral therapy era[END_REF][START_REF]The Opportunistic Infections Project Team of the Collaboration of Observational HIVERiEiE. CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load: A Longitudinal Cohort Study from COHERE[END_REF] By including viral suppression as a cofactor, it was found that Pneumocystis jirovecii prophylaxis could safely be stopped in an additional 40% of patients when compared with guidelines based exclusively on CD4 cell counts, [START_REF] Mocroft | Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/microL? Clinical infectious diseases : an official publication of the[END_REF] findings which informed both the American and European treatment guidelines [START_REF]Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America[END_REF][START_REF]European AIDS Clinical Society (EACS[END_REF] . The group is conducting similar analyses for toxoplasmosis and other OIs and intends to reassess the guidelines on the timing for discontinuing secondary prophylaxes against specific OIs. While the early start of cART in the course of cryptococcal meningitis has been shown to be harmful in some clinical trials performed in resource-limited settings [START_REF] Bisson | Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clinical infectious diseases : an official publication of the[END_REF][START_REF] Boulware | Timing of antiretroviral therapy after cryptococcal meningitis[END_REF] , in Western settings with advanced clinical monitoring this may not be the case. [START_REF] Lortholary | Fluconazole, with or without dexamethasone for experimental cryptococcosis: impact of treatment timing[END_REF] Current COHERE projects are examining the effect on mortality of the time of cART initiation after a diagnosis of cryptococcal meningitis or Toxoplasma gondii encephalitis. Preliminary results from a COHERE, NA-ACCORD and CNICS collaboration have shown that early cART did not increase mortality in AIDS patients with cryptococcal meningitis in high-income countries and overall mortality was lower than that reported by the clinical trials conducted in Africa. [START_REF] Ingle | Impact of ART on Mortality in Cryptococcal Meningitis Patients: High-Income Settings[END_REF] Current analyses explore how specific OIs influence long-term immune reconstitution, morbidity and mortality in the most recent cART era. The COHERE malignancy group has focused on defining the incidence, risk factors and prognosis of HIV-associated cancers in the cART era, with a focus on systemic non-Hodgkin lymphoma (NHL) and primary brain lymphoma (PBL), Hodgkin's lymphoma and, more recently, Kaposi's sarcoma. [START_REF] Bohlius | Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy[END_REF][START_REF] Bohlius | HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4(+) T-cell lymphocytes[END_REF][START_REF] Wyss | Kaposi Sarcoma in the Era of Combination Antiretroviral Therapy[END_REF] The incidence of non-Hodgkin's lymphoma, primary brain lymphoma and Kaposi's sarcoma were substantially reduced in patients on cART, and timely initiation of therapy at high CD4 cell counts is important for preventing these malignancies. [START_REF] Bohlius | Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy[END_REF][START_REF] Wyss | Kaposi Sarcoma in the Era of Combination Antiretroviral Therapy[END_REF] In contrast, the incidence of Hodgkin's lymphoma was not reduced by cART. Patients whose CD4 cell counts declined despite suppression of HIV-1 replication on cART were at increased risk of Hodgkin's lymphoma. [START_REF] Bohlius | HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4(+) T-cell lymphocytes[END_REF] Comparative analyses are planned in collaboration with the African regions of IeDEA. [START_REF] Egger | Cohort Profile: the international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa[END_REF]

Malignancy

Hepatitis

The immunological changes over the course of HCV treatment and their effect on mortality were estimated in 6,433 HIV-HCV-co-infected adults (≥16), 12% of whom had initiated HCV treatment (n=692 interferon and ribavirin; n=88 interferon alone). [START_REF]Effect of hepatitis C treatment on CD4+ T-cell counts and the risk of death in HIV-HCVcoinfected patients: the COHERE collaboration[END_REF] CD4 cell counts decreased over the first 12 weeks but stabilized from week 24 onwards with no negative impact on mortality. The group is poised to monitor the effect of the introduction of directacting antiviral agents in co-infected patients.

Socio-economic inequalities

The Socio-economic inequalities group studies differences in key outcomes by sex, race/ethnicity, migrant status and educational level as a proxy for socioeconomic position.

Even in European countries with universal health care systems, it has been documented that individuals with lower educational level do not benefit equally from timely cART initiation and have a poorer response to cART. [START_REF] Lodi | Delayed HIV diagnosis and initiation of antiretroviral therapy: inequalities by educational level, COHERE in EuroCoord[END_REF] Mortality in migrants has been found to be lower compared to native populations, which has been attributed to the "healthy migrant effect". COHERE's larger sample size has allowed this group to study mortality in men and women from multiple geographical origins separately, highlighting heterogeneity among migrant groups and revealing how certain groups are at an increased risk of mortality [START_REF]Mortality in migrants living with HIV in western Europe (1997-2013): a collaborative cohort study[END_REF] , work which was featured in the first issue of UNAIDS Science Now. The group plans to examine differences in cause-specific mortality by country of origin.

What are the main strengths and weaknesses?

COHERE in EuroCoord's infrastructure is a unique research platform which has prompted collaborations both within and beyond Europe. EuroCoord's cross-network work packages on data capture, HIV tuberculosis, migrant health and modelling and its interdisciplinary working groups (clinicians, virologists, epidemiologists, biostatisticians) have formalized this cross network collaboration and fostered intra-European capacity building. COHERE's further investment in data harmonization (HICDEP) has benefitted other regional collaborations.

Efforts to streamline data submission with the CASCADE and ART-CC cohort collaborations improved efficiency and reduced the workload of DMs. Finally, COHERE has provided excellent training opportunities for junior researchers (PhDs and Fellowships). COHERE's greatest strength is its size, enabling stratification of subgroups of interest 8 (e.g. across 10 age groups and sex-stratification) and the study of uncommon outcomes. [START_REF] Bohlius | Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy[END_REF] The robustness of COHERE's findings transcends Europe, benefiting the global HIV-patient community. COHERE data are highly representative of those in care in countries with large regional and national cohorts. Such cohorts enable COHERE to monitor trends across countries. However, adequate representation of marginalized groups such as migrant populations has become a challenge as a consequence of informed consent requirements in some countries as well as barriers to accessing care. [START_REF]Improving HIV data comparability in migrant populations and ethnic minorities in EU/EEA/EFTA countries: findings from a literature review and expert panel[END_REF] Although COHERE uses HICDEP, the heterogeneity in data quality remains an ongoing challenge. In collaboration with ART-CC [START_REF] May | Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)[END_REF] , COHERE has been an ideal platform for harmonizing the collection and validation of causes of deaths in HIV-1 infected individuals. Those interested in using COHERE data to conduct a project can download a COHERE Project Proposal Form and a Data Specification Form from our website (www.cohere.org).

Proposals from external investigators will undergo the same rigorous scrutiny as those from investigators within the study group (details outlined in the COHERE Manual of Operations, available at www.cohere.org).

Conclusion

COHERE is now a mature collaboration, which is unique in its size and coverage. It continues to produce new evidence on clinical outcomes, particularly AIDS-defining complications, late presentation and socio-economic inequalities, which inform clinical guidelines and public health policy recommendations. As PLWH live longer with a chronic infection, comparisons between them and cohorts of uninfected individuals are needed to disentangle the role of HIV infection from its long-term treatment and comorbidities, especially those linked to ageing.

Profile in a nutshell

• The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) is a project-driven cohort consortium that was set-up to address scientific questions that could not be addressed by single cohorts because of sample size requirements. • As a consortium of cohorts comprising clinic/hospital-based and interval cohorts, the frequency of patient follow-up varies. For clinic or hospital-based cohorts, average patient follow-up reflects current standards of care in those countries.

• COHERE compiles data on clinical characteristics, antiretroviral therapy and other medications, estimated date of HIV seroconversion, opportunistic infections, laboratory results and socio demographic data according to the requirements of projects. • The scientific questions addressed by COHERE are determined by consensus according to both their scientific relevance and originality (not being addressed elsewhere). • Individual cohorts may veto the use of their data in any new project.

F o r R e v i e w

O n l y    Follow-up and attrition: As a consortium of cohorts comprising clinic and interval cohorts, patient follow-up varies.

For clinic or hospital-based cohorts, average patient follow-up reflects current standards of care in those countries.

Design and Measures: COHERE is a cohort consortium that compiles data from 40 diverse cohorts of PLWH in Europe annually. The specific data merged is dictated by the eligibility criteria for included projects. Data categories commonly include clinical characteristics, antiretroviral therapy and other medications, estimated date of HIV seroconversion, opportunistic infections, laboratory results and socio demographic data.

Unique features : The submission of data to COHERE is facilitated by the use of the HIV Cohorts Data Exchange Protocol (HICDEP), a flexible data structure, developed in 2004, to guide the mapping of individual cohort data into a standard format to facilitate data merging, and the HIV Distributed Data Management Tool (http://www.hivddm.net/). A series of quality assurance checks are conducted centrally and cohorts address data inconsistencies before data are merged. Likely duplicate patient records between and within cohorts are identified using probability linkage and reconciled.

Reasons to be cautious : Although COHERE uses HICDEP, the heterogeneity in data quality remains a challenge. With a growing proportion of deaths in PLVH are caused by non-AIDS events, accurately monitoring these causes is key to identifying trends and evaluating risk factors. The "Coding Causes of Death in HIV" Protocol (CoDe), a uniform classification system for collecting and validating data on causes of death and contributing factors in HIV-1 infected patients is being implemented.

Collaboration and data access : External collaborators interested in conducting a project in COHERE should submit a proposal to the Regional Coordinating Centres for review by COHERE's governing bodies (see www.cohere.org).

Funding and competing interests

  Regional Coordinating Centres (RCCs), based at the University of Bordeaux's Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) in Bordeaux, France and the Center for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Rheumatology, Rigshospitalet, in Copenhagen, Denmark, maintain COHERE's infrastructure. The COHERE Steering Committee (SC) --composed of representatives fromthe participating cohorts --oversees the COHERE Collaboration, ensuring compliance with its principles; it also elects the Chair and the "Regional Representatives" to the COHERE

  Figure 1 presents the number of people living with HIV (excluding deaths) included in COHERE as of 31/12/2011 as a percentage of UNAIDS 2011 estimates of people living with HIV by country.COHERE includes both clinic/hospital-based cohorts of HIV-infected individuals, where data are extracted primarily from medical records in the context of routine care, and interval cohorts of specific populations of HIV-infected people, where data are collected at regular intervals that are unrelated to participants ongoing health care. Since people with HIV are seen regularly over a long period of time at a clinic/hospital, and are not just attending at times when they are symptomatic, the group of people seen at a given hospital naturally

  diseases.[START_REF] Engsig | Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery. Clinical infectious diseases : an official publication of the[END_REF] Future research will focus on new markers of the risk of morbidity and cause-specific mortality, outcomes in individuals treated for many years, and outcomes in people aging with HIV, particularly in the context of multi-morbidity and polypharmacy. The COHERE's Pursuing Later Treatment Options (PLATO) II project looked at the rate of development of virologic failure in adults, adolescents and children. When virologic failure has occurred with at least two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI), patients are said to have experienced triple class virologic failure (TCVF).

  proportion of deaths now caused by non-AIDS events, accurately monitoring causes of death is critical to identify trends and evaluate risk factors. The progressive implementation of the "Coding Causes of Death in HIV" Protocol (CoDe), a uniform classification system for collecting and validating (via a centralized review process) data on causes of death and contributing factors in HIV-1 infected patients, developed by the D:A:D collaboration, has become a priority.[START_REF] Kowalska | The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology[END_REF] Despite COHERE's demonstrated ability to evolve and adapt to respond to new research questions, it is now facing the challenge of expanding cohort and clinic-based databases to include clinical outcomes that were not initially of interest. As the cohort of PLWH in Europe ages, comorbidities, such as cardiovascular, metabolic, neurocognitive, and bone diseases, have become increasingly relevant to the study of prognosis in the era of cART. If COHERE and its contributing cohorts were formed today, more emphasis would be placed on linking HIV databases with other health databases (e.g. cancer registries, hospital or other administrative databases, etc.).COHERE from a patient's perspectiveCOHERE has maintained close ties with the patient community via its patient representative on the COHERE SC. Data from COHERE helped to demonstrate the value of high quality treatment strategies and enabled people living with HIV understand the evolving nature of the epidemic as well as face the ongoing challenges of growing older with HIV. Findings from COHERE have informed and guided the patient community's discussions with governments and authorities about treatment guidelines and standards of care.Can I get hold of the data? Where can I find out more? COHERE welcomes applications from Principal Investigators (PIs) of European cohorts interested in joining the COHERE collaboration. Interested cohorts must be willing to transform their data to fit HICDEP codes and adhere to the data submission timeline laid out Data Management SOP. COHERE DMs hold several explanatory webinars covering the data submission process to facilitate data transfer.

•

  COHERE has grown from 33 cohorts in 2005 to 40 in 2015. The 2014 merger, representing 14 projects, compiled data from 331 481 individuals from 34 European countries, including 2808 children (<13), representing 2 135 896 person-years of follow-up.

  Table 1a and 1b present a complete list of the cohorts, their characteristics and funding sources. All COHERE cohorts follow local ethical standards. The 2014 merger included data from 331 481, including 2,808 children (<13), representing 2 135 896 person-years of follow-up. Table 2a highlights the demographic characteristics and prognostic markers of HIV in those aged 13 and older enrolled in adult cohorts.

	Approximately a quarter of the COHERE sample is female (27%). The median age at
	inclusion is 35 [IQR:

What data are collected and how?

  On average, 25% of the COHERE 2014 sample met this definition of LTFU, with variation between cohorts. LTFU in paediatric cohorts was estimated among those under age 17 as COHERE has benefited from dynamic data management processes, which have evolved to accommodate new projects and scientific questions. COHERE's Data Managers (DMs) work with Project Leads and Statisticians to conduct preliminary surveys, feasibility studies and, occasionally, collect additional data. COHERE collects data on basic clinical information including: date of first HIV positive test, estimated date of seroconversion, cART and other medications, opportunistic infections, and laboratory results (CD4, CD8, plasma viral load values, hepatitis B and C serological tests, and HIV drug resistance tests), as well as sociodemographic data (see www.hicdep.org for more information about the definition of different

	many cohorts discontinue follow-up at age 18. LTFU among paediatric patients aged <17 (N
	= 1,960) was 20% overall and ranged from 1.8-22% across cohorts.
	F o
	r
	R variables). COHERE, via EuroCoord, conducts an inventory of data items and biological e samples collected by participating cohorts. The submission of data to COHERE is facilitated v i by the use of the HIV Cohorts Data Exchange Protocol (HICDEP), a flexible data structure, e developed in 2004, to guide the mapping of individual cohort data into a standard format to w facilitate data merging.
	O n
	l y
	8

  or an AIDS diagnosis, regardless of CD4 cell count, within six months of HIV-diagnosis. This definition was applied to 84,524 PLWH presenting for care between January 1 st , 2000 and June 30 Th 2011 in Europe. Late presentation was present in over half (53.8%) of the sample. It decreased over time in both Central and Northern Europe among homosexual men and heterosexuals, but, in contrast, increased over time in Southern Europe among female heterosexuals and male IDUs and in Eastern Europe among IDUs. Late presentation was associated with increased mortality, especially in the first year after diagnosis, with significant variation across Europe.[START_REF] Mocroft | Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)[END_REF] Further analyses study changes in late presentation within

	F o
	r
	R e v i e w
	O n
	l y

11 different regions and demographic groups since 2010.

•

  External collaborators interested in conducting a project in COHERE should submit a project proposal to the Regional Coordinating Centres in Bordeaux and Copenhagen for review by COHERE's governing bodies (see www.cohere.org for further information). Juan Berenguer, Julia Bohlius, Vincent Bouteloup, Heiner Bucher, Alessandro Cozzi-Lepri, François Dabis, Antonella d'Arminio Monforte, Mary-Anne Davies, Julia del Amo, Maria Dorrucci, David Dunn, Matthias Egger, Hansjakob Furrer, Marguerite Guiguet, Sophie Grabar, Ali Judd, Ole Kirk, Olivier Lambotte, Valériane Leroy, Sara Lodi, Sophie Matheron, Laurence Meyer, Jose M. Miró, Amanda Mocroft, Susana Monge, Fumiyo Nakagawa, Roger Paredes, Andrew Phillips, Massimo Puoti, Michael Schomaker, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut, Claire Thorne, Carlo Torti, Marc van der Valk, Linda Wittkop, Natasha Wyss. The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement n° 260694. A list of the funders of the participating cohorts can be found at www.COHERE.org. Box 1: COHERE's Principles • COHERE should neither threaten nor compete with the scientific agendas of participating cohorts/cohort collaborations. • The individual contributing cohorts must express their interest in participating in COHERE.

	F o F o Funding: F o F o F o F o
	r r r r r r
	R e v i e w R e v i e w R e v i e w R e v i e w R e v i e w R e v i e w
	O n O n O n O n O n O n
	l y l y l y l y l y l y
	20

18

Project Leads and Statisticians:

Table 1a :

 1a Description of the cohort type, eligibility criteria, period of enrolment, and location of data collection of the adult or mixed (adult/paediatric) cohorts participating in COHERE (circa 2015)

	Name of Cohort	Cohort Type	Eligibility Criteria	Enrolment period	Data Collection	N Sites/ Countries	Location of sites
			HIV+ age 13-21 and in paediatric				United
	AALPHI	Clinic & community-based, Interval cohort	care in UK, HIV-uninfected age 13-23, sibling of HIV-infected or has	06/01/2012 -12/31/2014	Prospectively	-	Kingdom (Region :
			HIV+ parent				England)
			HIV+ children included at birth
			(born to HIV-pregnant women
	ANRS CO10 EPF Interval cohort	enrolled in the CO1-EPF cohort), or, since 2005, at time of first HIV	09/07/1985 -	Prospectively	24	France
	CHIPS	care management in the clinical participating sites F o r Clinic-based, Hospital-based, Surveillance System All HIV+ children living in the UK/Ireland	04/01/2000-	Prospectively	-	United Kingdom (National), Ireland
	CoRISPE-cat CoRISpeS-Madrid Hospital-based Hospital-based	R e HIV+ <18 years at diagnosis v 01/01/2008 -i e w Both prospectively and retrospectively HIV+, infected before age 18 01/01/2002 -Both prospectively and retrospectively	13 59	(National) Spain (regions : Catalonia, Balearic Islands) Spain (national)
	KOMPNET Children Cohort Madrid PMTCT Cohort NENEXP	Clinic-based Hospital-based Hospital-based	HIV+, < 18 age HIV-1+ women during pregnnacy and their HIV-exposed infants HIV+ pregnant women & HIV-exposed children, HAART-exposed	06/01/2005 -1/2/0200 01/01/2000 -	Both prospectively and retrospectively O n Prospectively l 7 7 y Prospectively 12	Germany (National) Spain (Madrid) Spain (region:
			children until 18 month-old age.				Catalonia)
			All pregnancies in HIV+ women				United
	NSHPC	Surveillance System	living in the UK or Ireland, their exposed infants, and all children	01/01/1990 -	Prospectively	230	Kingdom & Ireland
			with HIV infection				(National)
	St Pierre Paediatric	Hospital-based	All HIV+ children/adolescents in care at site	01/01/2000 -	Both prospectively and retrospectively	1	Beligum (Brussels)

Table 1b :

 1b Description of the cohort type, eligibility criteria, period of enrolment, and location of data collection of paediatric or adolescent cohorts participating in COHERE (circa 2015)

						MSM**	Hetrosexual contact	IDU	Blood Products	Perinatal infected	Unknown
	AHIVCOS	4676	30505 1247 (27)	34 (28; 42)	3232 (69.1)	1727 (36.9)	1673 (35.8) 1008 (21.6)	88 (1.9)	5 (0.1)	175 (3.7)		3296 (70.5) 4.7 (3.8; 5.3)	3865 (82.7) 354 ( 175; 552)
	AMACS ANRS CO2 SEROCO ANRS CO3 AQUITAINE ANRS CO4 FHDH ANRS CO6 PRIMO ANRS CO8 COPILOTE ANRS CO13 HEPAVIH ATHENA Bonn*** Cologne*** CASCADE ClinSurv CoRIS*** CoRIS-MD*** DHK ECS EuroSIDA GEMES Haemo Infectious Disease Database (IDD) San Raffaele ICC (INMI Clinical Cohort) ICONA Italian MASTER Cohort Modena PISCIS SHCS St Pierre UK Collaborative HIV Cohort Study (UK CHIC) VACH	5359 1543 8457 87925 1563 1184 1146 21177 1978 1742 9037 17599 6466 3493 6367 5295 13384 94 2870 2947 9894 12728 1730 14202 10193 6925 47117 21582	35101 15766 63667 2202 (26) 870 (16) 452 (29) 637178 28899 (33) 7997 219 (14) 8761 280 (24) 4431 325 (28) 136563 4190 (20) 13125 377 (19) 1951 221 (13) 66196 1387 (15) 98130 3467 (20) 19589 1070 (17) 14953 990 (28) 49416 1573 (25) 5453 5295 (100) 27 (24; 31) 34 (27; 42) 30 (26; 36) 35 (29; 43) 35 (30; 43) 35 (29; 43) 36 (32; 43) 46 (42; 49) 39 (32; 46) 36 (30; 44) 37 (30; 45) 31 (26; 38) 38 (32; 46) 35 (29; 43) 35 (31; 39) 38 (31; 46) 85203 3854 (29) 36 (30; 43) 2210 5 (5) 21 (17; 24) 21618 485 (17) 36 (31; 43) 24752 823 ( 28) 37 (31; 43) 50626 2586 (26) 36 (31; 43) 74753 3458 (27) 37 (31; 44) 18239 560 (32) 33 (27; 41) 75297 3164 (22) 36 (31; 43) 70179 2961 (29) 37 (31; 44) 40047 2613 (38) 35 (28; 42) 291082 12923 (27) 34 (29; 40) F o r R e v i e w O n l y 4377 (81.7) 2707 (50.5) 1399 (26.1) 351 (6.5) 101 (1.9) 9 (0.2) 824 (53.4) 711 (46.1) 494 (32.0) 143 (9.3) 92 (6.0) 5354 (63.3) 3268 (38.6) 2398 (28.4) 1969 (23.3) 390 (4.6) 29 (0.3) 65261 (74.2) 28609 (32.5) 41088 (46.7) 9090 (10.3) 1560 (1.8) 298 (0.3) 1522 (97.4) 1101 (70.4) 366 (23.4) 4 (0.3) 1 (0.1) 873 (73.3) 464 (39.2) 405 (34.2) 194 (16.4) 30 (2.5) 805 (70.2) 155 (13.5) 184 (16.1) 688 (60.0) 71 (6.2) 1 (0.1) 15667 (74.0) 12323 (58.2) 6434 (30.4) 749 (3.5) 233 (1.1) 32 (0.2) 1512 (76.4) 937 (47.4) 502 (25.4) 200 (10.1) 189 (9.6) 5 (0.3) 926 (53.2) 1010 (58.0) 230 (13.2) 142 (8.2) 37 (2.1) 7288 (80.6) 5565 (61.6) 1467 (16.2) 1735 (19.2) 9055 (51.5) 2581 (14.7) 1622 (9.2) 125 (0.7) 38 (0.2) 5432 (84.0) 3728 (57.7) 1893 (29.3) 621 (9.6) 2334 (66.8) 492 (14.1) 755 (21.6) 1975 (56.5) 94 (2.7) 4776 (75.0) 2894 (45.5) 2409 (37.8) 586 (9.2) 84 (1.3) 8 (0.1) 5074 (95.8) 4736 (89.4) 320 (6.0) 16 (0.3) 8168 (61.0) 4645 (34.7) 4218 (31.5) 3665 (27.4) 169 (1.3) 72 (76.6) 94 (100.0) 2397 (83.5) 1257 (43.8) 620 (21.6) 274 (9.5) 8 (0.3) 4 (0.1) 2043 (69.3) 595 (20.2) 911 (30.9) 752 (25.5) 31 (1.1) 8 (0.3) 8882 (89.8) 2913 (29.4) 3933 (39.8) 2436 (24.6) 44 (0.4) 9558 (75.1) 2250 (17.7) 5074 (39.9) 2583 (20.3) 62 (0.5) 5 1252 (72.4) 334 (19.3) 732 (42.3) 545 (31.5) 11 (0.6) 1 (0.1) 11054 (77.8) 5105 (35.9) 5340 (37.6) 2481 (17.5) 47 (0.3) 60 (0.4) 7957 (78.1) 4106 (40.3) 4197 (41.2) 1000 (9.8) 80 (0.8) 9 (0.1) 4909 (70.9) 2158 (31.2) 3834 (55.4) 429 (6.2) 128 (1.8) 53 (0.8) 37616 (79.8) 23208 (49.3) 17178 (36.5) 1690 (3.6) 296 (0.6) 149654 5020 (23) 35 (30; 41) 16205 (75.1) 5914 (27.4) 6504 (30.1) 7089 (32.8) 76 (0.4) 14 (0.1)	792 (14.8) 103 (6.7) 403 (4.8) 7280 (8.3) 91 (5.8) 91 (7.7) 47 (4.1) 1406 (6.6) 145 (7.3) 323 (18.5) 270 (3.0) 4178 (23.7) 224 (3.5) 177 (5.1) 386 (6.1) 223 (4.2) 687 (5.1) 707 (24.6) 650 (22.1) 568 (5.7) 2754 (21.6) 107 (6.2) 1169 (8.2) 801 (7.9) 323 (4.7) 4745 (10.1) 1985 (9.2)	-	3821 (71.3) 4.5 (3.7; 5.1) 911 (59.0) 4.1 (3.6; 4.7) 2640 (31.2) 4.3 (3.0; 5.0) 52143 (59.3) 4.4 (3.5; 5.1) 1558 (99.8) 5.2 (4.5; 5.8) 1176 (99.3) 4.5 (3.7; 5.2) 1076 (93.9) 1.6 (1.6; 1.9) 19806 (93.5) 4.4 (2.6; 4.9) 1270 (64.2) 4.1 (2.6; 4.9) 573 (32.9) 4.3 (3.1; 5.0) 2655 (29.4) 4.9 (4.2; 5.6) 13904 (79.0) 4.6 (3.8; 5.2) 5504 (85.1) 4.7 (4.0; 5.2) 854 (24.4) 4.5 (3.0; 5.2) 3704 (58.2) 4.6 (3.7; 5.1) 895 (16.9) 3.9 (2.8; 4.6) 7782 (58.1) 4.0 (2.8; 4.8) ---2817 (98.15) 4.3 (3.3; 5.0) 1795 (60.9) 4.5 (3.1; 5.2) 8772 (88.7) 4.5 (3.8; 5.1) 9723 (76.2) 4.6 (3.9; 5.2) 718 (41.5) 4.6 (3.8; 5.3) 9878 (69.6) 4.5 (3.4; 5.2) 8028 (78.8) 4.4 (3.3; 5.1) 3238 (46.8) 4.5 (3.4; 5.0) 21366 (45.3) 4.4 (3.1; 5.1) 9344 (43.3) 4.8 (4.1; 5.3)	4244 (79.2) 348 ( 169; 548) 1526 (98.9) 480 ( 326; 669) 6205 (73.4) 330 ( 155; 516) 75154 (85.5) 337 ( 175; 520) 1558 (99.7) 514 ( 370; 666) 1173 (99.1) 273 ( 126; 424) 1071 (93.5) 450 ( 312; 647) 19736 (93.2) 360 ( 190; 550) 1653 (83.6) 365 ( 191; 563) 946 (54.3) 250 ( 50; 490) 4223 (46.7) 514 ( 368; 711) 14201 (80.7) 330 ( 160; 520) 5553 (85.9) 375 ( 194; 538) 1448 (41.5) 310 ( 140; 527) 4772 (74.9) 300 ( 120; 500) 1528 (28.9) 439 ( 301; 604) 12477 (93.2) 316 ( 165; 486) 3 (3.2) 130 ( 111; 748) 2698 (94.0) 420 ( 228; 620) 2696 (91.5) 315 ( 135; 525) 9104 (92.0) 401 ( 208; 593) 9927 (78.0) 304 ( 122; 511) 907 (52.4) 321 ( 133; 555) 10184 (71.7) 312 ( 136; 516) 10147 (99.5) 349 ( 179; 533) 4396 (63.5) 334 ( 169; 528) 25873 (54.9) 307 ( 140; 488) 10000 (46.3) 308 ( 129; 504)
	TOTAL	328,673	2112438 91,516 (28)	35 (30; 43) 235,370 (71.6) 127,231 (38.7) 121,555 (37.0) 44341 (13.5) 3861 (1.2) 875 (0.3) 30,810 (9.4) 199,247 (60.6) 4.5 (3.5; 5.1)	247,268 75 340 ( 170; 530)
	* Enrolment : measurements taken in the period six months prior to and one month after the variable "enrolment date"
	** Includes a small proportion of MSM+IDU
	*** Cohorts who have merged administratively but which represent 'one cohort' insofar as COHERE governance

Table 2a :

 2a Number of individuals, person-years of follow-up, patient demographics, prior AIDS status, mode of infection, median CD4 cell count and logarithm viral load in individuals older than 13 years old, (COHERE, 2014 merger) Cohort Profile: Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord Authors: COHERE in EuroCoord (A complete list of the members of the writing committee is available in the full version of the profile) Geneviève Chêne (geneviève.chêne@isped.u-bordeaux2.fr) Cite this as: The full version of this profile is available at IJE online and should be used when citing this profile. Cohort purpose: The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) was formed to pool and harmonize existing longitudinal data on people living with HIV (PLWH) collected across Europe to answer key research questions that, in the era of potent combination antiretroviral therapy (cART), could not be addressed adequately by individual cohorts. COHERE has grown from 33 cohorts in 2005 to 40 cohorts as of 2015. As COHERE is a project-based collaboration, the nature of annual mergers depends on the projects included. The 2014 merger compiled data from 331 481 individuals from 34 European countries, including 2808 children (<13), representing 2 135 896 person-years of follow-up. Approximately a quarter of the COHERE sample is female (27%). The median age at inclusion is 35 [IQR: 30, 43]. The primary mode of HIV transmission is sexual contact [homosexual/bisexual contact (38.7%), heterosexual contact (37%)], followed by injection drug use (13.5%). Overall, 71.6% of the sample had never had a clinical AIDS diagnosis before or during enrolment.

		Pocket Profile
	Cohort Title: Keywords: HIV, AIDS, cohort collaboration, prognosis, observational epidemiology N Person-years Female [N (%)] Median Age (IQR) No AIDS [N, (%)] prior to/during follow-up	Mode of infection [N (%)]	HIV RNA(log10 cp/ml) assessment at enrolment*, N (%)	Median HIV RNA (log10 cp/ml) at enrolment* (IQR)	CD4 cell count assessment at enrolment*, N (%)	Median CD4 cell count at enrolment* (IQR)
	Corresponding author: Cohort Basics:	F o r
		R e v i e w
		O n
		l y

  : The COHERE has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement n° 260694. Participating cohort funders are listed at www.COHERE.org.

	F o
	r
	R e v i e w
	O n
	l y

Conflicts of Interest

DC was a member of the French Gilead HIV board up until 2015