Simon Gregson
email: sajgregson@aol.com

Elizabeth Gonese

Timothy B Hallett

Noah Taruberekera

John W Hargrove

Ben Lopman

Elizabeth L Corbett

R Dorrington

S Dube

K Dehne

O Mugurungi

HIV decline due to

Keywords: Zimbabwe, HIV decline, HIV incidence, mortality, behaviour change

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Zimbabwe lies in southern Africa, the current epicentre of the global AIDS pandemic [START_REF]Report on the Global HIV/AIDS Epidemic[END_REF]. The first cases of AIDS were identified in the mid-1980s [START_REF] Dehne | Herpes Zoster as an indicator of HIV infection in Africa[END_REF] and by 1990 -the first year of antenatal-clinic (ANC) based surveillance -HIV prevalence exceeded 10%. The country's national estimate for HIV prevalence amongst adults in 2007 was 15.6% (range 14.9%-16.3%) [START_REF]Zimbabwe National HIV and AIDS Estimates[END_REF]. In part, the scale of the epidemic at country level reflects it's widely disseminated nature. HIV prevalence in small towns, farming estates and mines located in rural areas (22%) exceeds that in the major cities (14.5%), and prevalence is high even in subsistence farming areas (14.5%).

Recent data from ANC surveillance [START_REF] Mahomva | Revised estimates in HIV prevalence and trends from improving data in Zimbabwe, 2000-2004[END_REF] and general population surveys [START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF] suggest that Zimbabwe was the first country in the southern African region to record convincing declines in HIV prevalence.

A national decline in HIV prevalence is intrinsically a positive and important development because it represents a reduction in the burden of infection within the population. If maintained, it should translate into lower mortality over the next 5-10 years. However, declines in HIV incidence (new infections) and prevalence (existing infections) can occur through the natural dynamics of an epidemic [START_REF] Anderson | Infectious Diseases of Humans: Dynamics and Control[END_REF]. This is because, once the infection saturates and ages within the most vulnerable groups, the rate of transmission within the population as a whole tends to slow and can fall below the point where numbers of AIDS deaths exceed numbers of new infections. Declines in HIV prevalence (and even declines in HIV incidence) are therefore not a sufficient indication of sexual behaviour change affecting the course of the epidemic.

Programmatically, it is important to know whether changes in sexual behaviour contributed to the declines in HIV prevalence. We carried out a comprehensive review of the epidemiological data for Zimbabwe: (i) to confirm the existence of a decline in HIV prevalence; (ii) to establish the contributions of falling HIV incidence and rising mortality to the fall in HIV prevalence; and (iii) to assess whether changes in sexual behaviour contributed to the declines in HIV infection.

Methods

Review process

A review of epidemiological and behavioural data from secondary sources was carried out between November 2004 and June 2005. Formal request letters were sent to all organisations considered potential sources of surveillance data and follow-up inquiries were made by e-mail and telephone.

Meetings were held with the organisations concerned to identify relevant data. The review was

Data sources and data evaluation procedures

Details of the principal data sources reviewed are given in Table 1. The data were evaluated for quality and potential bias by examining the study designs and methods of data collection employed (including sample sizes and response and follow-up rates) and the appropriateness and consistency of methods of measurement used for individual indicators within and across studies [START_REF] Unaids | Evidence for HIV Decline in Zimbabwe: A Comprehensive Review of the Epidemiological Data[END_REF]. Reference was made, where possible, to in-depth studies of bias in the specific data sources [START_REF] Gregson | Study of bias in antenatal clinic HIV-1 surveillance data in a high contraceptive prevalence population in sub-Saharan Africa[END_REF][START_REF] Dorrington | Adult mortality in southern Africa using deaths reported by households: some methodological issues and results[END_REF][START_REF] Feeney | The impact of HIV/AIDS on adult mortality in Zimbabwe[END_REF][START_REF] Gregson | Informal confidential voting interview methods and temporal changes in reported sexual risk behaviour for HIV transmission in sub-Saharan Africa[END_REF]. The plausibility of the data was considered together with their external and internal consistency -including secondary analysis and triangulation of estimates from different sources and for related indicators.

Data on trends in HIV prevalence amongst pregnant women were obtained from the national antenatal clinic surveillance system for the period 2000 to 2006 [START_REF] Mahomva | Revised estimates in HIV prevalence and trends from improving data in Zimbabwe, 2000-2004[END_REF][START_REF]Antenatal Clinic HIV Surveillance Reports 2000-2006[END_REF] and were complemented by data from in-depth studies in urban (Harare, 1991 to 2002) [START_REF] Mbizvo | Trends in HIV-1 and HIV-2 prevalence and risk factors in pregnant women in Harare, Zimbabwe[END_REF][START_REF] Humphrey | HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation[END_REF][START_REF] Mahomed | Seroprevalence of HIV infection amongst antenatal women in greater Harare, Zimbabwe[END_REF] and rural areas (Manicaland, 1998 to 2005) [START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF]. A point estimate for HIV prevalence amongst the general population nationally in 2005 was obtained from the ZDHS 2005 [START_REF]Zimbabwe Demographic and Health Survey[END_REF]. No longitudinal data were available on national trends in the general population but data from community studies in Manicaland, Zimbabwe's eastern province, were examined [START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF]. Data on trends in HIV prevalence were also extracted from routine records maintained by the Zimbabwe National Blood Transfusion Service (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004), voluntary counselling and testing centres (2000)(2001)(2002)(2003)(2004) and the national prevention of mother-to-child transmission of HIV programme (2002)(2003)(2004). However, trends in these data were distorted by bias associated with the introduction, scale-up and selection criteria of these programmes (7) so the detailed results are not presented here.

To assess trends in HIV incidence in the national and rural populations, we examined trends in data on HIV prevalence in young adults [START_REF] Mahomva | Revised estimates in HIV prevalence and trends from improving data in Zimbabwe, 2000-2004[END_REF][START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF]. For urban populations, we compared estimates from prospective cohort studies of previously uninfected post-natal women (1999 [START_REF] Humphrey | HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation[END_REF] versus 1992 (17)) and male factory workers (2002-2003 (18) versus 1994-1995 (19)). Estimates for levels and trends in adult mortality were obtained from reports of deaths in the household and brother and sister (sibling) survival made in national censuses [START_REF]Census 1992: National Report: Zimbabwe Central Statistical Office[END_REF](21)[START_REF]Zimbabwe 1982 Population Census: Main Demographic Features[END_REF] and surveys [START_REF] Dorrington | Adult mortality in southern Africa using deaths reported by households: some methodological issues and results[END_REF][START_REF] Timaeus | Adult mortality in sub-Saharan Africa: evidence from Demographic and Health Surveys[END_REF], from vital registration records for the cities of Harare and Bulawayo [START_REF]Annual Report 2004[END_REF], and from population cohort data for rural areas in Manicaland [START_REF] Smith | Changing patterns of adult mortality as the HIV epidemic matures in Manicaland, eastern Zimbabwe[END_REF]. The possible contribution of selective international migration of HIV-positive individuals to changes in national levels of HIV prevalence was assessed using United Kingdom Health Protection Agency data on trends in Zimbabwe-born women tested at delivery at clinics in London (except south-west London) and the south-east and north-west regions of England between 2000 and 2006.

HIV in adults in Zimbabwe is acquired predominantly through heterosexual transmission [START_REF] Gregson | Informal confidential voting interview methods and temporal changes in reported sexual risk behaviour for HIV transmission in sub-Saharan Africa[END_REF][START_REF] Lopman | Evidence of absence: injection history and HIV incidence in rural Zimbabwe[END_REF].

Evidence for changes in sexual behaviour was assessed using data from the ZDHS surveys 1988 [START_REF]Zimbabwe Demographic and Health Survey[END_REF], 1994 [START_REF]Zimbabwe Demographic and Health Survey[END_REF], 1999 [START_REF]Zimbabwe Demographic and Health Survey[END_REF] and 2005 [START_REF]Zimbabwe Demographic and Health Survey[END_REF], a series of biannual knowledge, attitudes, practices and beliefs surveys commissioned by Population Services International (PSI) between 1997 and 2007 [START_REF]Knowledge, Attitudes, Beliefs and Practices on HIV/AIDS in Zimbabwe Survey Reports, 1997-2007[END_REF], the National Youth Reproductive Health Survey (ZNFPC) 1997 (31), the Zimbabwe Young Adult Survey 2001-2002 [START_REF]The Zimbabwe Young Adult Survey 2001-2002[END_REF] and the National OVC Baseline Survey 2004 [START_REF]Orphans and Other Vulnerable Children Survey: Baseline Survey for the Government of Zimbabwe and UNICEF Country Programme 2004-2005 in 21 Districts[END_REF]. Data on trends in behaviour in a general population cohort of 10,000 adults in Manicaland were also examined [START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF][START_REF] Gregson | Informal confidential voting interview methods and temporal changes in reported sexual risk behaviour for HIV transmission in sub-Saharan Africa[END_REF].

Statistical analysis

Estimates of HIV prevalence and incidence with 95% exact binomial confidence limits were calculated and compared using data from the sources described above.

Adult mortality rates were estimated for the period 1992-2002 from deaths reported by households in the 1992 and 2002 censuses. The method is described in detail elsewhere (9) but, essentially, the rates were calculated directly after adjusting the data on population size and deaths for bias in completeness of reporting. The results were compared with estimates from sibling data [START_REF] Timaeus | Adult mortality in sub-Saharan Africa: evidence from Demographic and Health Surveys[END_REF]. Crude death rates were calculated from local vital registration data [START_REF]Annual Report 2004[END_REF].

There being no data on the extent of migration of HIV-infected persons from Zimbabwe, we investigated the potential impact of international out-migration on recent trends in HIV prevalence, by fitting a published mathematical model [START_REF] Hallett | Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, Urban Kenya, Zimbabwe and Urban Haiti[END_REF] to the data on sexual behaviour (see below).

Projections were made and compared under the assumptions of no intentional behaviour change and:

(i) no migration; (ii) linear increase in migration from 0-5% of the total population per annum, 1997 to 2000, followed by constant 5% migration per annum; (iii) linear increase in migration from 0-10% of the total population per annum, 1997 to 2000, followed by constant 10% migration per annum; (iv) as for (iii) except that HIV-positive persons with symptomatic infection (AIDS) were 20-times more likely to migrate than uninfected individuals; (v) as for (iv) except that non-symptomatic HIVpositive individuals were also 20% more likely to migrate than uninfected individuals.

Indicators of the three main potential forms of sexual behaviour change (namely primary sexual abstinence, sexual partner acquisition, and condom use) were calculated and compared for the median age at first sex (with inter-quartile range) amongst 15-24 year-olds was calculated using a standard survival analysis technique [START_REF] Zaba | Age at first sex: understanding recent trends in African demographic surveys[END_REF]. For evidence of change in sexual partner acquisition rates, the proportion of sexually-experienced 15-29 year-olds reporting one or more non-regular sexual partner in the past 12 months was examined. For this analysis, a non-regular sexual partner was defined as a non-marital, non-cohabiting sexual partner. For evidence of change in condom use, the proportion of 15-29 year-olds with a non-regular partner in the past 12 months who reported having used a condom at last sexual intercourse with such a partner was examined. The age ranges 15-24 years and 15-29 years were used in the analyses so as to maximise the numbers of data sources included in the comparisons. To assess recent trends over a wider age-range, longitudinal data from the Manicaland study were examined.

Results

HIV prevalence

National antenatal HIV surveillance began in Zimbabwe in 1990. Initially, the selection of sites changed from year to year and few details are accessible on the field and laboratory methods used.

For some sites, large fluctuations were observed between successive rounds of surveillance. However, it appears that HIV prevalence increased steadily in the early to mid-1990s and stabilised in the late 1990s [START_REF] Unaids | Evidence for HIV Decline in Zimbabwe: A Comprehensive Review of the Epidemiological Data[END_REF]. HIV surveillance was strengthened in 2000 with an expansion in coverage, particularly in rural settings, more consistent site selection and field procedures, and detailed documentation of the procedures used (4). A Genscreen test was used for HIV testing in 2000. Subsequent evaluations of this test showed a low specificity under field conditions in Zimbabwe leading to over-estimates of HIV prevalence. Therefore, a new combined test algorithm was adopted from 2002 (4).

Based on results from the Genscreen test, HIV prevalence declined in 15-49 year-old pregnant women from 32% to 24% over the period 2000 to 2004 (Cochran-Armitage Trend Test, Z=10.6599, p-value (1-sided) <0.0001) (Fig. 1a) [START_REF]Antenatal Clinic HIV Surveillance Reports 2000-2006[END_REF]. Based on the combined test algorithm, HIV prevalence declined from 26% in 2002 to 18% in 2006. HIV prevalence fell in consecutive surveys in all age groups up to age 40 years (Fig. 1b). Median HIV prevalence for the 19 sentinel sites was 25% in 2002, 20.5% in 2004, and 17% in 2006 (UNAIDS fixed effects model for trend, p<0.0001). HIV prevalence in antenatal attendees fell between 2002 and 2006 in each of the three main socioeconomic strata -from 26.5% to 17% in urban areas, from 29% to 24% in other centres of commercial activity, and from 22% to 15% in rural areas [START_REF]Antenatal Clinic HIV Surveillance Reports 2000-2006[END_REF]. In the 12 surveillance sites that were used consistently from 1997 [START_REF] Asamoah-Odei | HIV prevalence and trends in sub-Saharan Africa: no decline and large sub-regional differences[END_REF] [START_REF] Unaids | Evidence for HIV Decline in Zimbabwe: A Comprehensive Review of the Epidemiological Data[END_REF].

In greater Harare, HIV prevalence in women attending antenatal and maternity clinics increased from 17% in 1991 to around 35% in 1999 before falling to 19.5% in 2004 [START_REF] Mahomva | Revised estimates in HIV prevalence and trends from improving data in Zimbabwe, 2000-2004[END_REF][START_REF] Humphrey | HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation[END_REF]. In rural Manicaland, there was a reduction in HIV prevalence in antenatal clinic attendees from 21% (95% CI, 19-24%) in 1998-2000 to 15% (13-17%) in 2003-2005 while, in the general population, HIV prevalence fell in men from 19.5% (18.5-21%) to 16.5% (15.5-17.5%) and in women from 26% (25-27.5%) to 20.5% (19.5-21.5%) [START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF].

Based on the antenatal surveillance data for urban, rural and other areas and Census data on the national population distribution, the 2005 national estimates for Zimbabwe put HIV prevalence in adults in 2005 at 20.1% (range 17-23.5%) [START_REF]Zimbabwe National HIV and AIDS Estimates[END_REF]. The ZDHS estimate for 2005 was slightly lower at 18.1% (95% CI, 17.4-18.8%) [START_REF]Zimbabwe Demographic and Health Survey[END_REF]. Using this point estimate and the antenatal clinic surveillance data, the 2007 national estimates report indicated that HIV prevalence had declined to 15.6% in 2007 (range 14.9-16.3%) from a peak of 29.3% in 1997 (3).

HIV incidence

HIV incidence measured in cohorts of pregnant women and male factory workers in Harare fell from 4.8 per 100 person years at risk (%) (95% CI, 3.1-6.5%) in 1992 (17) to 3.4% (3.0-3.8%) in 1999 [START_REF] Humphrey | HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation[END_REF] and from 3.0% (2.5-3.5%) in 1994-95 [START_REF] Mbizvo | HIV seroincidence and correlates of seroconversion in a cohort of male factory workers in Harare, Zimbabwe[END_REF] to 1.3% (1.0-1.8%) [START_REF] Corbett | HIV incidence during a cluster-randomized trial of two strategies providing voluntary counselling and testing at the workplace, Zimbabwe[END_REF] in 2002-03, respectively (Fig. 2a) [START_REF] Unaids | Evidence for HIV Decline in Zimbabwe: A Comprehensive Review of the Epidemiological Data[END_REF]. There were differences in the age-composition of the study populations used in these comparisons. However, declines in HIV incidence in most age-groups were observed in both studies [START_REF] Unaids | Evidence for HIV Decline in Zimbabwe: A Comprehensive Review of the Epidemiological Data[END_REF] and the decline in male factory workers was still observed after adjusting for age (age-adjusted IRR, 0.50; 95% CI, 0.36-0.70).

HIV prevalence among young people aged 15-24 years can provide useful indications of trends in HIV incidence [START_REF] Zaba | Monitoring the AIDS epidemic using HIV prevalence data among young women attending antenatal clinics: prospects and problems[END_REF]. Nationally, HIV prevalence in 15-24 year-old women attending antenatal clinics fell from 30% in 2000 to 20% in 2004 (using the Genscreen test) and from 21% in 2002 to 13% in 2006 (using the combined test algorithm) (Fig. 2b). Declines occurred between 2002 and 2006 in all socioeconomic locations (urban, rural and other). In the Manicaland study, HIV prevalence in the general population fell between 1998-2003 from 5.4% (95% CI, 4.5-6.5%) to 3.3% (2.6-4.1%) in men aged 17-24 years and from 16.5% (14.9-18.1%) to 8.8% (7.9-9.7%) in women aged 15-24 years (5).

Applying back-calculation methods to data on registered deaths in Harare (see below), Lopman and Gregson [START_REF] Lopman | When did HIV incidence peak in Harare, Zimbabwe? Backcalculation from mortality statistics[END_REF] found that HIV incidence in Harare may have peaked between 1988 and 1990. [START_REF] Murimwa-Moyo | Mortality levels, patterns and trends in the city of Harare, Zimbabwe[END_REF] and in rural areas in the early-to mid-1990s [START_REF] Gregson | Recent upturn in mortality in rural Zimbabwe: evidence for an early demographic impact of HIV-1 infections?[END_REF]. National estimates from sibling survival histories collected in Demographic and Health surveys indicate that the probability of death before age 60 years among those who survive to age 15 years increased from 30% and 21%, for men and women, respectively, in the late 1980s to around 70% for men and 60% for women, by the early 2000s (Fig 3a) [START_REF]Zimbabwe Demographic and Health Survey[END_REF][START_REF] Timaeus | Adult mortality in sub-Saharan Africa: evidence from Demographic and Health Surveys[END_REF]. The estimates of mortality based on the Census data are somewhat higher but again indicate a rapid and substantial rise in adult mortality during the 1990s.

In Harare, the crude death rate, estimated from vital registration data, also rose rapidly during the 1990s (Fig. 3b). The subsequent stabilisation and reduction may reflect increased urban-rural and international migration associated with the economic decline that occurred from the late 1990s. In Bulawayo, the crude death rate continued to rise up to 2002. The subsequent trend is unclear due to a switch to the use of burial records. The levels of the vital registration mortality estimates are consistent with those derived from the Census. In rural Manicaland, male and female adult mortality levelled off at around 30 deaths per thousand person years between 2001 and 2005, following earlier increases [START_REF] Smith | Changing patterns of adult mortality as the HIV epidemic matures in Manicaland, eastern Zimbabwe[END_REF].

International migration

Migration of Zimbabweans to the Diaspora has been extensive since the late 1990s and selective outmigration of HIV-positive individuals could have contributed to the decline in HIV prevalence.

However, the results of the mathematical model simulations suggest that, even with very large numbers of migrants, this effect can only have been small unless extreme assumptions are made. For example, the final scenario shown in Fig. 4a (long dashed lines) reflects a situation in which, as the epidemic peaks, 10% of the national population migrates every year, with persons with AIDS 20times more likely to migrate than uninfected individuals, and with 10% of asymptomatic HIVpositive individuals aware of their status and 3-times as likely to migrate as uninfected individuals.

There are two main destinations of recent migrants from Zimbabwe: the United Kingdom (UK), prevalence in these women remained stable at around 9-11% (Fig. 4b), which suggests that HIV prevalence in Zimbabweans migrating to western countries could be lower than amongst nonmigrants. Migrants to southern and central African countries may have a different socioeconomic profile due to the shorter distances and greater possibilities for unauthorised border-crossings. However, data from Manicaland suggest that, within Zimbabwe at least, rural out-migrants have similar socioeconomic characteristics and vulnerability to HIV/AIDS prior to migrating to nonmigrants [START_REF] Mundandi | No difference in HIV incidence and sexual behavior between migrants and non-migrants in Manicaland, Zimbabwe[END_REF].

Sexual behaviour change

Consistent estimates of median age at first sex were available from 11 different national surveys covering the period 1994 to 2007 for men and 12 surveys covering 1988 to 2007 for women. In both cases, median age at first sex fluctuated within the range 17-20 years with no clear evidence for a trend over time (Fig. 5a). In the ZDHS surveys, the proportion of males aged 15-19 years who reported having ever had sex fell from 33% in 1994 to 27% in 2005 (p=0.005) while there was no change in this proportion amongst females. In Manicaland, the proportions of males aged 17-19 years and females aged 15-17 years who reported having ever had sex fell from 45% to 27% (p<0.001) and 21% to 9% (p<0.001), respectively, between 1998-2000 and 2001-2003 (5).

Surveys differed in the indicators used to measure faithfulness -either in the definition of non-regular or casual partner or in the length of period over which the indicator was measured. The indicator used most frequently was one or more non-regular partners (defined as being a non-marital, non-cohabiting partner) in the past 12 months, which could be compared for 15-29 year-olds for both sexes in 2 ZDHS surveys (1999 and 2005) and 5 PSI surveys (2001,2003,2005,2006 and 2007) (Fig. 5b). The ZDHS data indicate reductions in reports of non-regular partners from 57% (95% CI, 53.5-60%) and 15.5% (14-17%) in 1999 to 47% (44-50%) and 14% (13-16%) in 2005, for men and women, respectively. In addition, the percent of sexually-experienced men (aged 15-49 years) that reported having paid for sex in the past year fell from 7.2% (95% CI. 5.6-8.9%) in 1999 to 3.6% (3.0-4.2%) in 2005. For men, the PSI estimates are consistently lower than the corresponding ZDHS estimates possibly due to differences in the survey methods (e.g. in the wordings of the questions). However, these data also show a substantial reduction in non-regular partners between 2001 (32%, 95% CI, 29-35%) and 2003 (21%, 19-23.5%), after which the percentages remained close to the 2003 level through to 2007. For women, the estimates are unstable but, again, suggest a reduction between 2001 (17%, 14.5-20%) and 2003 (8%, 7-9%). In the Manicaland study, the proportion of men (aged 17-54 years) reporting a recent casual partner fell by 49% over the period 1998 to 2003, from 25.9% (95% CI, 24.1-27.9%) to 13.2% (11.5-15.0%). A smaller decline was observed for women (aged 15-44 years) -from 7.5% (6.5-8.6%) to 5.9% (4.9-7.0%) [START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF].

Discussion

We assembled, analysed and assessed, for the first time, all previously published and unpublished data available on trends in HIV prevalence in Zimbabwe from the onset of the epidemic in the 1980s. These data provide a consistent picture of a decline in HIV prevalence starting in the late 1990s and continuing up to 2006. We also presented the first comparisons of data on HIV incidence measured in cohort studies of comparable populations at different time-points and new analyses of data from multiple sources on trends in mortality since the onset of the HIV epidemic. These data show that the decline in HIV prevalence was driven by a combination of falling HIV incidence and high mortality.

HIV incidence fell after 1990, reflecting the saturation of infection within high risk groups that occurs as epidemics mature in heterogeneous populations, and led to prevalence stabilising by 1997-2002 [START_REF] Anderson | Infectious Diseases of Humans: Dynamics and Control[END_REF]. However, mathematical model simulations of the HIV epidemic in Zimbabwe carried out in the review (details published separately [START_REF] Hallett | Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, Urban Kenya, Zimbabwe and Urban Haiti[END_REF][START_REF] Hallett | Is there evidence for behaviour change affecting the course of the HIV epidemic in Zimbabwe? A new mathematical modelling approach[END_REF]) indicated that the pace of the decline in HIV prevalence could not have occurred without changes in behaviour or other risk factors, probably between 1999 and 2004. By conducting secondary analyses and triangulating all data available on sexual behaviour, we found evidence for substantial reductions in the proportion of individuals (particularly men) reporting non-regular partners, occurring precisely during this period. Whilst condom use within nonregular partnerships did not increase after 1999, the pre-existing high level of use (which the Manicaland data suggest was often consistent by this time) contributed to the subsequent low proportion of men having sex without condoms with non-regular partners. Furthermore, earlier increases in condom use contributed to the fall in HIV incidence by reducing the reproductive rate of transmission closer to the tipping point (i.e. the point at which the net reproductive number R t <1) at which further reductions in risk behaviour can have a substantial impact on the epidemic [START_REF] Garnett | Factors controlling the spread of HIV in heterosexual communities in developing countries: patterns of mixing between different age and sexual activity classes[END_REF]. The data sources provide inconsistent information on trends in age at first sex but even the largest delays

F o r R e v i e w O n l y
found in the Manicaland data are too small to have contributed to the overall decline in HIV prevalence [START_REF] Hallett | Behaviour change in generalised HIV epidemics: impact of reducing cross-generational sex and delaying age at sexual debut[END_REF].

The extent of recent international migration from Zimbabwe is substantial albeit difficult to quantify. However, the limited data did not provide evidence for selective migration of HIV-infected individuals and model simulations of alternative scenarios for the extent and selectivity of migration showed it was unlikely to have contributed greatly to the decline in HIV prevalence.

The high level of internal consistency in the wide range of data and indicators examined in the review indicates that the main findings are robust. However, the detailed results should be treated with some caution since estimates for trends in the different indicators can be subject to temporal changes in bias. The national sentinel surveillance HIV prevalence trends may reflect improvements in diagnostic testing and logistical procedures (4) whilst the trends in HIV incidence and sexual behaviour could be distorted by differences in survey procedures and, in the latter case, by changes in social desirability bias [START_REF] Catania | Methodological problems in AIDS behavioural research: influences on measurement error and participation bias in studies of sexual behaviour[END_REF]. The estimates of trends in mortality are adjusted for temporal variations in the coverage of census, survey and vital registration systems but some residual inaccuracy may remain and estimates more distant from the survey date may be distorted by recall bias [START_REF] Timaeus | Adult mortality in sub-Saharan Africa: evidence from Demographic and Health Surveys[END_REF].

Zimbabwe is the first country in southern Africa to record a convincing decline in HIV prevalence.

Prevalence declines in urban and rural areas of Ethiopia and Rwanda, and parts of Malawi and Niger have also been associated with changes in sexual behaviour (most notably reductions in partner numbers), whereas epidemic stabilisation in other countries (including Cote d'Ivoire and Burundi) could feasibly only reflect the natural evolution of the epidemic [START_REF]Report on the Global HIV/AIDS Epidemic[END_REF]. The controversy that has surrounded the earlier decline in Uganda [START_REF] Parkhurst | The Ugandan success story? Evidence and claims of HIV-1 prevention[END_REF][START_REF] Stoneburner | Population-level HIV declines and behavioral risk avoidance in Uganda[END_REF][START_REF] Wawer | Declines in HIV prevalence in Uganda: not as simple as ABC[END_REF] demonstrated the need for comprehensive collation and careful review of epidemiological and behavioural data to establish a sound basis for consensus on the contributions of reductions in HIV incidence and sexual risk behaviour to declines in HIV prevalence. The current study shows that these contributions probably have been substantial in Zimbabwe and therefore are very encouraging. Further analysis and triangulation, including qualitative investigations, will be necessary to elucidate the reasons why behaviour changed. The decline in HIV prevalence also reflects a continuing period of sustained crisis-level mortality and, in 2008, it is still the case that one in every seven adults in Zimbabwe is infected with a life-threatening virus. There is much, therefore, that remains to be done.

  authors with guidance from participants in meetings of the UNAIDS Reference Group on Estimates, Modelling and Projections meeting (16 November 2004) and local stakeholders (7 June 2005 and 30 May 2008).

  above, for each sex separately. For evidence of change in sexual abstinence,

  MortalityMortality began to rise in urban areas of Zimbabwe in the late 1980s

  Australasia and other western countries; and South Africa, Botswana and other neighbouring countries in southern and central Africa. There are no reliable estimates of numbers of migrants to either of these destinations since 2000. Numbers of Zimbabwe-born women tested at antenatal clinics in the United Kingdom increased between 2000 and 2004 and fell slightly thereafter but HIV

  Data on condom use at last sex with a non-regular sexual partner in the past 12 months were available for 15-29 year-olds from 9 surveys spanning the period 1999 to 2006 (Fig.5c). Condom use with non-regular partners was already high by the late 1990s. Thereafter, the ZDHS (and Young Adult Survey 2002) estimates are generally lower than those from the PSI surveys but neither show a clear trend. In Manicaland, consistent condom use with recent casual partners remained at quite a high level in men (aged 17-54 years) -41.6% (95% CI, 33.7-49.4%) in 1998-2000 versus 42.2% (37.1-47.3%) in 2001-03 -and increased in women (aged 15-44 years) from 26.2% (18.9-33.6%) to 36.5% (26.0-46.9%)[START_REF] Gregson | HIV decline associated with behaviour change in eastern Zimbabwe[END_REF].

Fig. 1 .

 1 Figure captions

Fig. 2 .

 2 Fig. 2. Decline in HIV incidence, Zimbabwe, 1990-2006. (a) HIV incidence measured in cohorts of postnatal women ( Sources: Mbizvo (17); ZVITAMBO (14)) and male factory workers (• Sources: ZAPP (19); BRTI (18)), Harare; and (b) HIV prevalence in pregnant women attending for routine check-ups at antenatal clinics, 15-24 years, 2000-2006 (12).

Fig. 3 .

 3 Fig. 3. Increase in mortality, Zimbabwe. (a) Probability of death between ages 15 and 60 years ( 45 q 15 ) estimated from sibling survival histories collected in the Zimbabwe Demographic and Health Surveys, 1988-2005/06 (16, 27-29) and from household data collected in national censuses 1982, 1992, 1997 and 2002 (20-22); and (b) crude death rate, Harare and Bulawayo, estimated from vital registration data on numbers of deaths per annum and Census estimates of population numbers, 1980-2004 (24). For Bulawayo, the estimates (shown by the dashed lines) for 1981 to 1991 were read from a figure in the Bulawayo City Health Report 1992; for 2003 and 2004, the estimates were derived from burial records rather than records of registered deaths.

Fig. 4 .

 4 Fig. 4. Migration and HIV prevalence decline: (a) Mathematical model projections of the potential impact of international out-migration on trends in HIV prevalence in Zimbabwe: (1) no migration; (2) linear increase in migration from 0-5% of the total population per annum, 1997-2000, followed by constant 5% migration per annum; (3) linear increase in migration from 0-10% of the total population per annum, 1997-2000, followed by constant 10% migration per annum; (4) as for (3) except that HIV-positive persons with symptomatic infection (AIDS) are 20-times more likely to migrate than uninfected individuals; (5) as for (4) except that non-symptomatic HIV-positive individuals are also (on average) 20% more likely to migrate than uninfected individuals. All scenarios assume no intentional behaviour change. (b) HIV prevalence in Zimbabwe-born women at delivery in the United Kingdom, 2000-2003 (Source: United Kingdom Health Protection Agency). Includes women tested in London (except South-West London), and the South-East and North-West regions of England (95% CIs).

Fig. 5 .

 5 Fig. 5. Trends in sexual behaviour: Estimates from national surveys: (a) median age at first sex for respondents aged 15-24 years at date of survey by sex calculated using survival analysis, (b) proportions of respondents aged 15-29 years at interview reporting a non-regular sexual partner in past 12 months, (c) proportions of respondents aged 15-29 years at interview with a non-regular sexual partner in the past 12 months who reported using a condom during last sex with such a partner. Estimates shown in graph (a) with inter-quartile range and graphs (b) and (c) with 95% CI. Sources:Zimbabwe Demographic and Health Surveys[START_REF]Zimbabwe Demographic and Health Survey[END_REF][START_REF]Zimbabwe Demographic and Health Survey[END_REF][START_REF]Zimbabwe Demographic and Health Survey[END_REF][START_REF]Zimbabwe Demographic and Health Survey[END_REF], Population Services International[START_REF]Knowledge, Attitudes, Beliefs and Practices on HIV/AIDS in Zimbabwe Survey Reports, 1997-2007[END_REF], Zimbabwe Ministry of Health and Child Welfare[START_REF]The Zimbabwe Young Adult Survey 2001-2002[END_REF] and UNICEF[START_REF]Orphans and Other Vulnerable Children Survey: Baseline Survey for the Government of Zimbabwe and UNICEF Country Programme 2004-2005 in 21 Districts[END_REF].

  Combined test HIV result Combined test HIV result (median and IQR for 19 sites) Combined test HIV result Combined test HIV result (median and IQR for 19 sites)

  , median HIV prevalence in 15-44 year-olds rose from 24% (IQR,

	23-40%) in 1997 to 33.5% (29-39%) in 2000 before falling to 28% (23-35%) in 2002, 22.5% (19-
	28%) in 2004 and 20% (19-26%) in 2006
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Acknowledgements

We are grateful to S Greby, S Haders, G Bicego (CDC), F Cowan (University College London), C Benedikt (UNFPA), R Monasch, S Saito (UNICEF), M Wellington (University of Zimbabwe) and G Woelk (ZICHIRE) for facilitating access to data; B Zaba and E Slaymaker for advising on methods of data analysis; K Marsh for assistance with data analysis; and other participants in the UNAIDS Reference Group on Estimates, Modelling and Projections meeting (16 November 2004) and the local stakeholders meetings (7 June 2005 and 30 May 2008) who advised on interpretation of the data.

Conflict of interest: None declared.

KEY MESSAGES

• HIV prevalence fell substantially in Zimbabwe between the late 1990s and 2006.

• Reductions in the proportions of men (particularly) and women with non-regular sexual partners and sustained high levels of condom use were recorded during this period and contributed to the decline in HIV prevalence.

• Selective migration of infected individuals was not a major factor contributing to the HIV decline in Zimbabwe.

• AIDS mortality contributed to the stabilisation and decline in HIV prevalence in Zimbabwe and remained at crisis levels in the mid-2000s.