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 impact of antiretroviral therapy on adult mortality in rural Tanzania.

OBJECTIVE: To describe the impact of antiretroviral therapy (ART) on mortality rates among adults participating in an HIV community cohort study in north-west Tanzania. METHODS: Serological and demographic surveillance rounds have been undertaken in a population of approximately 30,000 people since 1994. Free HIV care including ART has been available since 2005. Event history analysis was used to compare mortality rates among HIV-negative and HIV-positive adults in the 5-year period before and after the introduction of ART. Crude and adjusted hazard ratios were calculated using exponential regression models. Interaction between time period and HIV status was assessed to investigate whether there was a non-linear relationship between these two variables. RESULTS: Male and female mortality patterns varied over the pre- and post-ART period. In women, the crude death rate fell for both HIV negatives and HIV positives hazard rate ratio (HRR = 0.71; 95%CI 0.51-0.99 and HRR = 0.68; 95%CI: 0.46-0.99, respectively). For men, the mortality among the HIV negatives increased (HRR = 1.47; 95%CI: 1.06-2.03) while the decline in mortality among the HIV positives (HRR = 0.77; 95%CI 0.52-1.13) was not statistically significant. The largest decrease in HIV-positive mortality over the two periods was among the 30- to 44-year-old age group for women and among the 45- to 59-year-old age group for men. CONCLUSION: There has been a modest effect on mortality in the study population following the introduction of free ART 5 years ago. Improving access to treatment and placing greater focus on retaining individuals on treatment are essential if the full potential of treatment for reducing HIV-related mortality is to be realised

The effect of antiretroviral therapy provision on all-cause, AIDS and non-AIDS mortality at the population level--a comparative analysis of data from four settings in Southern and East Africa.

OBJECTIVE: To provide a broad and up-to-date picture of the effect of antiretroviral therapy (ART) provision on population-level mortality in Southern and East Africa. METHODS: Data on all-cause, AIDS and non-AIDS mortality among 15-59 year olds were analysed from demographic surveillance sites (DSS) in Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and the Africa Centre (South Africa), using Poisson regression. Trends over time from up to 5 years prior to ART roll-out, to 4-6 years afterwards, are presented, overall and by age and sex. For Masaka and Kisesa, trends are analysed separately for HIV-negative and HIV-positive individuals. For Karonga and the Africa Centre, trends in AIDS and non-AIDS mortality are analysed using verbal autopsy data. RESULTS: For all-cause mortality, overall rate ratios (RRs) comparing the period 2-6 years following ART roll-out with the pre-ART period were 0.58 (5.9 vs. 10.2 deaths per 1000 person-years) in Karonga, 0.79 (7.2 vs. 9.1 deaths per 1000 person-years) in Kisesa, 0.61 (6.7 compared with 11.0 deaths per 1000 person-years) in Masaka and 0.79 (14.8 compared with 18.6 deaths per 1000 person-years) in the Africa Centre DSS. The mortality decline was seen only in HIV-positive individuals/AIDS mortality, with no decline in HIV-negative individuals/non-AIDS mortality. Less difference was seen in Kisesa where ART uptake was lower. CONCLUSIONS: Falls in all-cause mortality are consistent with ART uptake. The largest falls occurred where ART provision has been decentralised or available locally, suggesting that this is important

Wicked but worth it: student perspectives on socio-hydrology

harvestPolicy AnalysisMulti Actor System

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

Uptake of services for prevention of mother-to-child transmission of HIV in a community cohort in rural Tanzania from 2005 to 2012.

BACKGROUND: Estimates of population-level coverage with prevention of mother-to-child transmission (PMTCT) services are vital for monitoring programmes but are rarely undertaken. This study describes uptake of PMTCT services among HIV-positive pregnant women in a community cohort in rural Tanzania. METHODS: Kisesa cohort incorporates demographic and HIV sero-surveillance rounds since 1994. Cohort data were linked retrospectively to records from four Kisesa clinics with PMTCT services from 2009 (HIV care and treatment clinic (CTC) available in one facility from 2008; referrals to city hospitals for PMTCT and antiretroviral treatment (ART) from 2005). The proportion of HIV-positive pregnant women residing in Kisesa in 2005-2012 who accessed PMTCT service components (based on linkage to facility records) was calculated per HIV-positive pregnancy and by year, with adjustments made to account for the sensitivity of the linkage algorithm. RESULTS: Out of 1497 HIV-positive pregnancies overall (to 849 women), 26% (n = 387/1497) were not linked to any facility records, 35% (n = 519/1497) registered for ANC but not HIV services (29% (n = 434/1497) were not tested at ANC or diagnosed previously), 8% (n = 119/1497) enrolled in PMTCT but not CTC services (6 % (n = 95/1497) received antiretroviral prophylaxis), and 32% (n = 472/1497) registered for CTC (14% (n = 204/1497) received ART or prophylaxis) (raw estimates). Adjusted estimates for coverage with ANC were 92%, 57% with HIV care, and 29 % with antiretroviral drugs in 2005-2012, trending upwards over time. CONCLUSIONS: Population-level coverage with PMTCT services was low overall, with weaknesses throughout the service continuum, but increased over time. Option B+ should improve coverage with antiretrovirals for PMTCT through simplified decisions for initiating ART, but will rely on strengthening access to CTC services

Is the risk of HIV acquisition increased during and immediately after pregnancy? A secondary analysis of pooled HIV community-based studies from the ALPHA network.

BACKGROUND: Previous studies of HIV acquisition in pregnancy have been in specific population groups, such as sero-discordant couples which have shown an increased risk of HIV acquisition during pregnancy and studies of sexually active women where the results have been ambiguous. However these studies are unable to tell us what the overall impact of pregnancy is on HIV acquisition in the general population. METHODS: Data from six community-based HIV cohorts were pooled to give 2,628 sero-conversions and a total of 178,000 person years of observation. Multiple imputation was used to allow for the uncertainty of exact sero-conversion date in surveillance intervals greater than the length of a pregnancy. Results were combined using Rubin's rules to give appropriate error bounds. The analysis was stratified into two periods: pre- and post- widespread availability of prevention of mother-to-child HIV transmission services. This allows us to assess whether there is reporting bias relating to a person's knowledge of their own HIV status which would become more widespread in the latter time period. RESULTS: Results suggest that women while pregnant have a lower risk of acquiring HIV infection over all periods (HRR 0.79, 95%CI 0.70-0.89) than women who were not pregnant. There is no evidence for a difference in the rate of HIV acquisition between postpartum and non-pregnant women (HRR 0.92 95%CI 0.84-1.03). DISCUSSION: Although there may be immunological reasons for increased risk of HIV acquisition during pregnancy, at a population level this study indicates a lower risk of HIV acquisition for pregnant women. Pregnant women may be more likely to be concordant with their current sexual partner than non-pregnant women, i.e. either already HIV positive prior to the pregnancy or if negative at the time of becoming pregnant more likely to have a negative partner

HIV acquisition in pregnancy: implications for mother-to-child transmission at the population level in sub-Saharan Africa.

INTRODUCTION: A recent sero-discordant couple study showed an elevated risk of HIV-acquisition during the pregnancy/postpartum period per-condomless-coital-act. This, along with previous studies, has led to concern over possible increased risk of mother-to-child (vertical) transmission, due to the initial high viral load in the first months after seroconversion, in a time when the woman and health services may be unaware of her status. This study looks at whether behavioural differences during the pregnant/postpartum period could reduce the impact of elevated risk of HIV acquisition per-condomless-coital-act at the population level. METHODS: We used data from 60 demographic and health surveys from 32 sub-Saharan African countries. Using the HIV status of couples, we estimated differences in serodiscordancy between HIV-negative women who were pregnant/postpartum compared to those who were not pregnant/postpartum. We compare the risk of sexual activity over the pregnant/postpartum period to those not pregnant/postpartum. Using these risks of serodiscordancy and sexual activity along with estimates of increased HIV risk in the pregnancy/postpartum period per-condomless-coital-act, we estimated a population-level risk of HIV acquisition and acute infection, during pregnancy/postpartum compared to those not pregnant/postpartum. RESULTS: Sexual activity during pregnancy/postpartum varies considerably. In general, sexual activity is high in the first trimester of pregnancy, then declines to levels lower than among women not pregnant/postpartum, and is at its lowest in the first months postpartum. Adjusted for age and survey, pooled results show HIV-negative pregnant women are less likely to have an HIV-positive partner compared to those not pregnant/postpartum (risk ratio (RR) = 0.78, 95% CI = 0.68-0.89) and comparing the postpartum period (RR = 0.85, 95% CI = 0.73-0.99). Estimated population-level risk for HIV acquisition and acute infection in pregnancy/postpartum was lower than would be inferred directly from per-condomless-coital-act estimates in most countries, over the time of most risk of mother-to-child transmission, though there was variation by country and month of pregnancy/postpartum. CONCLUSIONS: Estimates of population-level HIV acquisition risk in sub-Saharan Africa should not be taken directly from per-condomless-coital-act studies to estimate vertical transmission. Changes in sexual behaviour and differences in HIV-serodiscordancy during pregnancy/postpartum reduce the impact of increased risk of HIV acquisition per-condomless-coital-act, this will vary by region