Planning for the integration of fertility or prenatal care services with clinical HIV services requires a clear understanding of which women will become pregnant and at what rates. In this observational study of HIV-positive women in urban South Africa, we found that pregnancy was relatively common after HAART initiation, reaching an estimated cumulative incidence of 52% among women who were 18–25 when they initiated HAART.
A recent study by Myer et al. reported on the incidence of 589 pregnancies after initiation of HAART among 4,531 women in seven African countries [6
]. However, the generalizability of these findings may be somewhat limited by the fact that all these women entered care through prevention of mother-to-child transmission of HIV programs; by virtue of pregnancy, they may have been healthier than women who initiated HAART because they were sick [18
] and—for this reason and others—may have been more likely to experience subsequent pregnancy. In addition, the main results reported by Myer et al. were a mix of very high and low pregnancy-incidence settings, with by-country rates ranging from 21.7 per 100 person-years in Rwanda to 3.3 (95% CL 2.6, 4.2) per 100 person-years in three urban sites in South Africa, from both pre- and post-HAART initiation. Our results show an overall higher rate of 5.2 per 100 person-years in only women who have initiated HAART. Our work shows similar incidence rates by age category: Myer et al. reported a rate of 11.5 (95% CL 9.4, 14.0) per 100 person-years among women under age 25 and on antiretroviral therapy; we reported a rate of 10.4 (8.2, 13.3) per 100 person-years. The relatively high rates of pregnancy seen here, taken in context with recent results suggesting that pregnancy during HAART is associated with increased rates of virologic failure [11
], point to the need to better integrate reproductive healthcare services with provision of antiretroviral therapy.
Previous work [11
] and theory [20
] both suggest that women who are pregnant at baseline may respond to HAART in substantially different ways compared with nonpregnant women, in part because their initiation onto HAART may have more to do with their pregnancy status rather than their immune status. Here, we had insufficient data to evaluate whether predictors of incident pregnancy differ substantially by baseline pregnancy status. We saw a higher crude rate of incident pregnancy in women who were pregnant at baseline (6.2 versus 5.0 pregnancies per 100 person-years), but a slight reduction in relative rate (IRR 0.80, 95% CL 0.62, 1.03) in multivariate analysis. The lowered relative rate in multivariate analysis may be the result of a desire to space out births and/or a period of lowered risk of new pregnancy immediately postpartum (e.g., due to lactational amenorrhea). However, prevalent pregnant women are about twice as likely to be lost to followup as non-prevalent pregnant women; this finding should, therefore, not be overinterpreted.
There are several limitations of this work. Chief among these is our lack of data on use of contraception. However, it is likely that contraceptive use in this setting is likely to be lower than in the South African sites evaluated by Myer et al., as that work examined women who were accessing prevention of mother-to-child transmission services [6
]. The present work deals with a general adult population, in which access to contraceptives may be more typical of the experience of an average South African woman presenting for general HIV care [21
]; further, contraceptives are not offered at the pharmacy where TLC patients receive their antiretroviral medications, which is likely to further depress usage. Future studies will assess the impact and efficacy of contraception in this setting as well as assess unmet needs for contraception in the adult female population of this clinic. In addition, we analyzed observational data from a clinical database, and thus misclassification of exposure (particularly, start and end dates of pregnancies), outcome, and other factors cannot be ruled out. However, our sensitivity analyses support the results of our main analysis, and as noted above the TLC database has been previously validated for accuracy [12
A final, and critical, limitation is that, while it is tempting to interpret the adjusted rate ratios reported in as statements of causality (e.g., if we were to intervene on factor X, the rate of pregnancy would change by Y), such causal statements are not justifiable without substantial further assumptions and caveats [22
]. Without further study, the numbers reported in should be considered associations and predictions, not statements of causality.
In this large study of nearly 6,000 antiretroviral therapy-naïve women initiating HAART in Johannesburg, we found a high rate of pregnancy, especially among younger women. With very high numbers of HIV-infected young women in South Africa [5
], incident pregnancy among women receiving HAART is an important issue with implications both for maternal response to HAART [11
] as well as potentially for mother-to-child-transmission of HIV. It will be critical in coming years both to integrate contraceptive counseling and/or antenatal care into settings where HAART is provided [23
] as well as to ensure that women who get reproductive or antenatal care in other facilities are able to transition between care centers smoothly and without becoming lost to care. In addition, such a high rate of pregnancy makes it critical that we better understand the impact and timing of pregnancy after HAART initiation on outcomes of HAART, as well as of pregnancy in both mother and child.