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.
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 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).
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.
Citation: Marston M, Newell ML, Crampin A, Lutalo T, Musoke R, Gregson S, et al. (2013) 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. PLoS ONE 8(12): e82219. https://doi.org/10.1371/journal.pone.0082219
Editor: Dimitrios Paraskevis, University of Athens, Medical School, Greece
Received: June 11, 2013; Accepted: October 24, 2013; Published: December 26, 2013
Copyright: © 2013 Marston et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Analysis based on data pooled by the ALPHA network, as supplied by: the Rakai study, managed by Rakai Health Sciences Program, in Uganda and supported by grants NIAID R01 A134265; NICHD RO1 HD 050180; the Henry M. Jackson Foundation and the Bill and Melinda Gates Institute for Population and Reproductive Health at Johns Hopkins University; the Kyamulibwa general population cohort, managed by MRC/UVRI, in Uganda; the Kisesa open cohort, managed by the TAZAMA programme at NIMR (Mwanza), in Tanzania with funding from the Global Fund for AIDS, TB and Malaria through the Tanzania National Coordinating Mechanism and the Ministry of Health& Social Welfare; the Karonga Prevention Study, managed by LSHTM in Malawi; principally funded by the Wellcome Trust; the Manicaland study, managed by Imperial College and the BioMedical Research Training Institute, in Zimbabwe principally funded by Wellcome Trust (grant 084401/Z/07/Z); the Africa Centre surveillance cohort in Umkhanyakude, managed by ACHPS/University of KwaZulu-Natal, in South Africa with surveillance activities funded by the Wellcome Trust (grant 082384/Z/07/Z). The ALPHA network itself is funded by the Wellcome Trust (grant 090959/Z/09/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Fertility rates are high in many sub-Saharan African countries and, thus, a significant proportion of woman-years are spent pregnant . Evidence regarding the risk of acquisition of HIV infection at and shortly after the time of pregnancy is conflicting [2-8]. An increased risk of HIV acquisition in pregnant women has implications for health services as the increased viral load in acute infection would expose the fetus to higher risk of in utero mother-to-child transmission . This would also have implications for HIV epidemic modelling as estimates for paediatric HIV would need to be revised upwards.
A number of prospective studies from Eastern and Southern Africa have assessed the risk of HIV incidence during pregnancy. A multisite study of sero-discordant couples found that HIV incidence was, in univariate analysis, two-fold higher in pregnant than in not-pregnant women; however, after adjusting for age, any unprotected sex in last month, and contraceptive use, the risk difference was reduced and no longer statistically significant . A similar study in Uganda restricted to married sero-discordant couples reported a non-significant increase in the HIV acquisition rate in pregnant women . Other studies included women regardless of the partners’ HIV status; in a Ugandan study of sexually-active women the risk of HIV-1 acquisition was doubled during pregnancy . However, in an HIV prevention trial enrolling women from a number of health services and community venues in southern Africa there was no increased risk of HIV-1 in pregnant women . A study in Uganda and Zimbabwe, in which women from family planning sites were enrolled, found no increased risk of HIV acquisition in pregnant women in the pooled analysis overall, and actually showed some evidence of a protective pregnancy effect in one of the sites in the study after adjusting for covariates . Further studies have shown a possible increased HIV incidence during pregnancy [10-12], others showed a risk comparable to the general population of a similar age [13,14].
A number of studies have investigated HIV incidence in the postpartum period, again with somewhat conflicting results. In Malawi, a prospective study of women enrolled after delivery found HIV acquisition was increased in the first year postpartum decreasing subsequently ; this was also the case in Zimbabwe  and Rwanda . The authors of the latter study suggested that the decrease could be partly due to a cohort selection bias with those remaining uninfected for longer having a lower risk of infection . Other studies have not reported an increased risk in the postpartum period [2,15].
The rate of HIV acquisition and differences between pregnant, postpartum and non-pregnant women at a population level will depend not only on the risk of infection per sexual act with an HIV positive partner, but also on the level of discordance in pregnant and non-pregnant couples and the differences in sexual behaviour between these groups. Therefore results from the studies outlined above cannot be generalised to the general population.
Population-based HIV cohort studies are ideally placed to provide generalisable estimates of the risk of HIV during pregnancy in the community; this paper uses data from six such cohorts from eastern and southern Africa. We aim to assess the population-level HIV incidence during pregnancy and the post-partum period, adjusting for age. The results will inform organisations that provide estimates to health services providers.
Data come from six sites: Karonga (Karonga prevention study), Kisesa (TAZAMA), Masaka (UK Medical Research Council and Uganda Virus Research Institute), Rakai (Rakai Health Sciences), Manicaland (Imperial College London and the Biomedical Research and Training Institute) and uMkhanyukude (Africa Centre). Data collection was sufficiently similar to allow pooled analyses, with allowance for unobserved heterogeneity between sites.
The Karonga Demographic Surveillance Study (DSS) is located in rural northern Malawi; it was established in 2002 and has a total population of around 35,000, population-based HIV testing in the DSS was undertaken in four annual rounds from 2007-2011  and average adult HIV prevalence between these dates was 8% . The Kisesa cohort study is situated in rural north-west Tanzania, it was established in 1994 and has a population of around 30,000 it contains a small trading centre located on the main road from Mwanza town to the border of Kenya which runs through the centre of the study area, average HIV prevalence between 1994 and 2010 was 6% [18,19]. The Masaka DSS is located in rural south west Uganda and was established in 1989. Its initial population was around 10,000 which then increased to 18,000 when 10 villages were added to the census area . Average HIV prevalence between 1989 and 2011 was 8% . The Rakai Health Sciences Program runs the Rakai Community Cohort Study (RCCS), with an adult population of between 12,000-16,000. For this analysis, data were collected from 1999 with 2002/3 adult HIV prevalence reported to be 11.4 % . The Manicaland study was established in 1993. A prospective household census (population size approximately 37,000) and general population cohort survey (10,000-12,000) were initiated in 12 locations spread across three districts in 1998, with follow-ups being conducted every 2 or 3 years. They comprise two small towns, four agricultural estates, two roadside settlements and four subsistence farming areas. Overall adult HIV prevalence has fallen in these areas from 24% in the late 1990s to 14% at the end of the 2010s . The Africa Centre Surveillance study was established in 2000 in uMkhanyakude, in rural KwaZulu-Natal, South Africa; each round covers approximately 90,000 resident and non-resident household members in approximately 12,000 households, with a key-household respondent , an individual HIV surveillance for resident adults (≥15 years) was added in 2003 and adult HIV prevalence in 2012 was around 28% and annual incidence in the 15-50 year age group for women was about 5% .
Each of the six sites contributing data to the pooled analysis has received ethical clearance from the appropriate local ethics review bodies, and from the corresponding Institutional Review Boards for studies which had collaborating partnerships with Northern Universities.
Annually re-certified ethics permission for the Africa Centre DSS and nested individual HIV surveillance among consenting adults obtained from the Biomedical Research Ethics Committee at the Nelson Mandela School of Medicine, University of KwaZulu-Natal. Detailed written informed consent obtained for participation in the HIV surveillance.
Ethical approval granted by the National Health Sciences Research Committee of Malawi and the ethics Committee of the London School of Hygiene and Tropical Medicine. Written informed consent obtained for HIV testing.
Ethical approval for each survey round of the Kisesa cohort study granted by the Tanzanian Medical Research Coordinating Committee and the Ethics Committee of the London School of Hygiene and Tropical Medicine. Prior to 2006, verbal consent obtained directly from all study participants (aged 15 and over), due to low literacy rates among the study population. Consent witnessed and documented for each study participant by a member of the sero-survey team. From 2006 onward, consent was again obtained directly from all study participants, however written consent option introduced, for those able to provide this.