Measuring the impact of antiretroviral therapy roll-out on population level fertility in three African countries

BackgroundUNAIDS official estimates of national HIV prevalence are based on trends observed in antenatal clinic surveillance, after adjustment for the reduced fertility of HIV positive women. Uptake of ART may impact on the fertility of HIV positive women, implying a need to re-estimate the adjustment factors used in these calculations. We analyse the effect of antiretroviral therapy (ART) provision on population-level fertility in Southern and East Africa, comparing trends in HIV infected women against the secular trends observed in uninfected women.MethodsWe used fertility data from four community-based demographic and HIV surveillance sites: Kisesa (Tanzania), Masaka and Rakai (Uganda) and uMkhanyakude (South Africa). All births to women aged 15–44 years old were included in the analysis, classified by mother’s age and HIV status at time of birth, and ART availability in the community. Calendar time period of data availability relative to ART Introduction varied across the sites, from 5 years prior to ART roll-out, to 9 years after. Calendar time was classified according to ART availability, grouped into pre ART, ART introduction (available in at least one health facility serving study site) and ART available (available in all designated health facilities serving study site). We used Poisson regression to calculate age adjusted fertility rate ratios over time by HIV status, and investigated the interaction between ART period and HIV status to ascertain whether trends over time were different for HIV positive and negative women.ResultsAge-adjusted fertility rates declined significantly over time for HIV negative women in all four studies. However HIV positives either had no change in fertility (Masaka, Rakai) or experienced a significant increase over the same period (Kisesa, uMkhanyakude). HIV positive fertility was significantly lower than negative in both the pre ART period (age adjusted fertility rate ratio (FRR) range 0.51 95%CI 0.42–0.61 to 0.73 95%CI 0.64–0.83) and when ART was widely available (FRR range 0.57 95%CI 0.52–0.62 to 0.83 95%CI 0.78–0.87), but the difference has narrowed. The interaction terms describing the difference in trends between HIV positives and negatives are generally significant.ConclusionsDifferences in fertility between HIV positive and HIV negative women are narrowing over time as ART becomes more widely available in these communities. Routine adjustment of ANC data for estimating national HIV prevalence will need to allow for the impact of treatment

The effects of HIV on fertility by infection duration: evidence from African population cohorts before antiretroviral treatment availability.

OBJECTIVES: To estimate the relationship between HIV natural history and fertility by duration of infection in east and southern Africa before the availability of antiretroviral therapy and assess potential biases in estimates of age-specific subfertility when using retrospective birth histories in cross-sectional studies. DESIGN: Pooled analysis of prospective population-based HIV cohort studies in Masaka (Uganda), Kisesa (Tanzania) and Manicaland (Zimbabwe). METHODS: Women aged 15-49 years who had ever tested for HIV were included. Analyses were censored at antiretroviral treatment roll-out. Fertility rate ratios were calculated to see the relationship of duration of HIV infection on fertility, adjusting for background characteristics. Survivorship and misclassification biases on age-specific subfertility estimates from cross-sectional surveys were estimated by reclassifying person-time from the cohort data to simulate cross-sectional surveys and comparing fertility rate ratios with true cohort results. RESULTS: HIV-negative and HIV-positive women contributed 15 440 births and 86 320 person-years; and 1236 births and 11 240 000 person-years, respectively, to the final dataset. Adjusting for age, study site and calendar year, each additional year since HIV seroconversion was associated with a 0.02 (95% confidence interval 0.01-0.03) relative decrease in fertility for HIV-positive women. Survivorship and misclassification biases in simulated retrospective birth histories resulted in modest underestimates of subfertility by 2-5% for age groups 20-39 years. CONCLUSION: Longer duration of infection is associated with greater relative fertility reduction for HIV-positive women. This should be considered when creating estimates for HIV prevalence among pregnant women and prevention of mother-to-child transmission need over the course of the HIV epidemic and antiretroviral treatment scale up

Changes in Fertility at the Population Level in the Era of ART in Rural Malawi.

INTRODUCTION: HIV reduces fertility through biological and social pathways, and antiretroviral treatment (ART) can ameliorate these effects. In northern Malawi, ART has been available since 2007 and lifelong ART is offered to all pregnant or breastfeeding HIV-positive women. METHODS: Using data from the Karonga Health and Demographic Surveillance Site in Malawi from 2005 to 2014, we used total and age-specific fertility rates and Cox regression to assess associations between HIV and ART use and fertility. We also assessed temporal trends in in utero and breastfeeding HIV and ART exposure among live births. RESULTS: From 2005 to 2014, there were 13,583 live births during approximately 78,000 person years of follow-up of women aged 15-49 years. The total fertility rate in HIV-negative women decreased from 6.1 [95% confidence interval (CI): 5.5 to 6.8] in 2005-2006 to 5.1 (4.8-5.5) in 2011-2014. In HIV-positive women, the total fertility rate was more stable, although lower, at 4.4 (3.2-6.1) in 2011-2014. In 2011-2014, compared with HIV-negative women, the adjusted (age, marital status, and education) hazard ratio was 0.7 (95% CI: 0.6 to 0.9) and 0.8 (95% CI: 0.6 to 1.0) for women on ART for at least 9 months and not (yet) on ART, respectively. The crude fertility rate increased with duration on ART up to 3 years before declining. The proportion of HIV-exposed infants decreased, but the proportion of ART-exposed infants increased from 2.4% in 2007-2010 to 3.5% in 2011-2014. CONCLUSIONS: Fertility rates in HIV-positive women are stable in the context of generally decreasing fertility. Despite a decrease in HIV-exposed infants, there has been an increase in ART-exposed infants

Mortality trends in the era of antiretroviral therapy: evidence from the Network for Analysing Longitudinal Population based HIV/AIDS data on Africa (ALPHA)

Background:The rollout of antiretroviral therapy (ART) is one of the largest public health interventions in Eastern and Southern Africa of recent years. Its impact is well described in clinical cohort studies, but population-based evidence is rare.Methods:We use data from seven demographic surveillance sites that also conduct community-based HIV testing and collect information on the uptake of HIV services. We present crude death rates of adults (aged 15–64) for the period 2000–2011 by sex, HIV status, and treatment status. Parametric survival models are used to estimate age-adjusted trends in the mortality rates of people living with HIV (PLHIV) before and after the introduction of ART.Results:The pooled ALPHA Network dataset contains 2.4 million person-years of follow-up time, and 39114 deaths (6893 to PLHIV). The mortality rates of PLHIV have been relatively static before the availability of ART. Mortality declined rapidly thereafter, with typical declines between 10 and 20% per annum. Compared with the pre-ART era, the total decline in mortality rates of PLHIV exceeds 58% in all study sites with available data, and amounts to 84% for women in Masaka (Uganda). Mortality declines have been larger for women than for men; a result that is statistically significant in five sites. Apart from the early phase of treatment scale up, when the mortality of PLHIV on ART was often very high, mortality declines have been observed in PLHIV both on and off ART.Conclusion:The expansion of treatment has had a large and pervasive effect on adult mortality. Mortality declines have been more pronounced for women, a factor that is often attributed to women's greater engagement with HIV services. Improvements in the timing of ART initiation have contributed to mortality reductions in PLHIV on ART, but also among those who have not (yet) started treatment because they are increasingly selected for early stage disease

Age patterns of HIV incidence in eastern and southern Africa: a collaborative analysis of observational general population cohort studies

Background: As the HIV epidemic in sub-Saharan Africa matures, evidence about the age distribution of new HIV infections and how this has changed over the epidemic is needed to guide HIV prevention. We assessed trends in age-specific HIV incidence in six population-based cohort studies in eastern and southern Africa, reporting changes in average age at infection, age distribution of new infections, and birth cohort cumulative incidence.Methods: We used a Bayesian model to reconstruct age-specific HIV incidence from repeated observations of individuals’ HIV serostatus and survival collected among population HIV cohorts in rural Malawi, South Africa, Tanzania, Uganda, and Zimbabwe. The HIV incidence rate by age, time and sex was modelled using smooth splines functions. Incidence trends were estimated separately by sex and study. Estimated incidence and prevalence results for 2000-2017, standardised to study population distribution, were used to estimate average age at infection and proportion of new infections by age.Findings: Age-specific incidence declined at all ages, though the timing and pattern of decline varied by study. The average age at infection was higher in men (cohort means: 27·8-34·6 years) than women (cohort means: 24·8-29·6 years). Between 2000 and 2017, the average age at infection increased slightly: cohort means 0·5-2·8 years among men and -0·2-2·5 years among women. Across studies, between 38-63% (cohort means) of women’s infections were among 15-24-year-olds and between 30-63% of men’s infections were in 20-29-year-olds. Lifetime risk of HIV declined for successive birth cohorts.Interpretation: HIV incidence declined in all age groups and shifted slightly, but not dramatically, to older ages. Disproportionate new HIV infections occur among 15-24-year-old women and 20-29-year-old men, supporting focused prevention in these groups. But 40-60% of infections were outside these ages, emphasising the importance of providing appropriate HIV prevention to adults of all ages.Funding: Bill and Melinda Gates Foundation

ALPHA HIV Incidence and Mortality Data, Kisesa 1994-2016

This dataset is created from harmonising longitudinal population-based demographic surveillance and repeated serological survey data collected by an Kisesa HIV open cohort Study in Mwanza, Tanzania. The data harmonisation is coordinated by the ALPHA Network which curates individual-level data on demographic surveillance, verbal autopsy interviews, serological and sexual behaviour surveys, and individually-linked data from HDSS and medical facilities

The effects of HIV on fertility by infection duration: evidence from African population cohorts before antiretroviral treatment availability

OBJECTIVES: To estimate the relationship between HIV natural history and fertility by duration of infection in East and Southern Africa before the availability of antiretroviral therapy, and assess potential biases in estimates of age-specific sub-fertility when using retrospective birth histories in cross-sectional studies. DESIGN: Pooled analysis of prospective population-based HIV cohort studies in Masaka (Uganda) Kisesa (Tanzania), and Manicaland (Zimbabwe). METHODS: Women aged 15-49 who had ever tested for HIV were included. Analyses were censored at antiretroviral treatment roll out. Fertility rate ratios were calculated to see the relationship of duration of HIV infection on fertility, adjusting for background characteristics. Survivorship and misclassification biases on age-specific subfertility estimates from cross-sectional surveys were estimated by reclassifying person time from the cohort data to simulate cross-sectional surveys and comparing fertility rate ratios to true cohort results. RESULTS: HIV negative and positive women contributed 15,440 births and 86320 person years; and 1,236 births and 11240 thousand person years respectively to the final dataset. Adjusting for age, study site and calendar year, each additional year since HIV sero conversion was associated with a 0.02 (95%CI 0.01-0.03) relative decrease infertility for HIV-positive women. Survivorship and misclassification biases in simulated retrospective birth histories resulted in modest underestimates of sub-fertility by 2-5% for age groups 20-39y. CONCLUSION: Longer duration of infection is associated with greater relative fertility reduction for HIV-positive women. This should be considered when creating estimates for HIV prevalence among pregnant women and PMTCT need over the course of the HIV epidemic and ART scale-up

Translating global health research aims into action: the example of the ALPHA network

There is increasing consensus on the importance of strengthening global health research to meet health and development goals. Three key global health research aims are to ensure that research (i) addresses priority health needs, (ii) contributes to policy development, and (iii) adds value to investments in developing countries through South-South collaboration and capacity-strengthening in the South. The ALPHA network (Analysing Longitudinal Population-based HIV/AIDS data on Africa) is an illustrative example of how these global health research aims can be translated into action. The network facilitates additional collaborative HIV epidemiological research among six independent research projects in Africa studying population-based cohorts. Under the first of the earlier mentioned aims, the network addresses key epidemiology research issues in HIV/AIDS which are crucial to making progress and monitoring progress in the response against HIV/AIDS. Under the second aim, the network's scientific programme of research has contributed to strengthening the evidence base on HIV epidemiology in Africa and has informed policy development in areas such as targeted HIV prevention, social support, monitoring epidemic response and epidemic forecasting. Under the third aim, investment in the network has added value to the research investment in the individual projects through capacity development among African researchers as well as through the collaborative research outputs of the individual projects. Lessons from the network are relevant to collaborations facing similar challenges in other areas of global health research. These include the importance of establishing transparent and efficient governance for research collaborations, developing advance consensus on data sharing, ensuring effective communication for networking and demonstrating the added value of research investment in South-South collaborations