In this study, we describe the incidence of pregnancy among HIV-infected women initiating ART. Baseline pregnancy prevalence was 9% and pregnancy incidence was 9.40 per 100 WYs during a median of 3.8 years of follow-up after initiation of ART. By one, two, and three years after ART initiation, the overall cumulative probability of pregnancy in this cohort was 12%, 20%, and 28%, respectively.
Among women reporting pregnancy at baseline, over one-third were diagnosed with HIV during the pregnancy. The remaining two-thirds became pregnant after knowing their HIV status but before ART initiation. For these women, conception and pregnancy were likely associated with increased risks of poor health outcomes and of HIV transmission to sexual partners.
The observed pregnancy incidence of 9.40 pregnancies per 100 WYs is within the range of comparable regional studies of reproductive-aged women initiating ART 
. This incidence is lower than that reported in studies employing inclusion criteria that affect probability of pregnancy, including younger age group 
and non-use of injectable contraception 
We cannot directly assess whether pregnancy incidence among this cohort differs from HIV-infected women not on ART. A retrospective study of pregnancy incidence among women receiving HIV treatment and care at the referral clinic for this cohort reported a similar pregnancy incidence (8.6 pregnancies per 100 WYs) with no difference by ART use 
. Other regional studies enrolling HIV-positive ART-naïve women have reported similar 
or higher 
pregnancy incidence. A large multi-country study found a lower incidence of subsequent pregnancy among women initiating ART during pregnancy with substantial variability in rates by individual country setting 
. The recent results of the DART trial, which enrolled women initiating ART in Uganda and Zimbabwe, similarly reported a lower incidence of pregnancy (4.4 per 100 woman years [95% CI 4.0–4.9] 
The pregnancy incidence observed among UARTO participants is lower than for the general Ugandan population. The age-specific fertility rate of women aged 30–34 years in Uganda is 24.8 births per 100 women 
which, while not directly comparable, is well above a pregnancy rate of 9.40 pregnancies per 100 WYs found in this study. This is consistent with data that suggest HIV-infected women have lower fertility than HIV-uninfected women 
The pregnancy incidence observed in this and other studies, coupled with estimates from the same site reporting that 85% of HIV-positive women do not intend to become pregnant 
but have low rates of contraceptive use 
and regional estimates that most pregnancies among women with HIV are reported as unplanned and/or unwanted 
reinforces the need for improved, comprehensive reproductive counselling that promotes contraception to avoid unwanted pregnancies and safer conception for women who want pregnancy.
We observed that incidence of pregnancy varied with time since ART initiation, with highest incidence in periods proximal to ART initiation (with a peak in pregnancy incidence between 6–12 months) and lower incidence in periods distal to ART initiation. Four years after ART initiation, we observed a resurgence in pregnancy incidence, largely accounted for by recurrent pregnancies. Other regional studies have reported an independent effect of ART on increasing pregnancy incidence over time compared with ART-naïve women 
. This is consistent with studies from North America and Europe reporting an increase in pregnancy and birth rates among HIV-positive women after widespread availability of ART 
. Whether increased pregnancy incidence after ART is a result of biological (e.g., improved fecundity) or behavioural change (e.g. improved sexual drive with restored health, increased fertility intentions) is not well understood but is likely due to a combination of factors 
. These data underscore the need to incorporate comprehensive reproductive counselling for women upon HIV diagnosis and prior to ART initiation, rather than waiting and expecting women to initiate discussions with healthcare providers once they intend to become pregnant 
Independent, time-varying predictors of incident pregnancy in this cohort include younger age and disclosure of HIV status to a primary sexual partner. Younger age has been associated with higher fertility desire 
, lower contraceptive use 
, higher fecundity 
, strong societal and partner pressures towards early and frequent childbearing 
, and higher incident pregnancy in several studies of both HIV-positive women 
and women in general 
As shown in .b, among women under 35 years of age, the probability of pregnancy within three years of ART initiation was 42%, compared with 11% probability among women older than 35. While all women of reproductive age are at risk for pregnancy events and should receive routine counselling to discuss reproductive goals and services to prevent unintended pregnancies and reduce periconception-related HIV transmission risks, these data suggests that younger women are a critical target population.
Interviews with pregnant HIV-positive women in Kampala explored the complex role that HIV serostatus disclosure plays in pregnancy decision-making 
. Disclosure is a precondition for encouraging a partner to engage in HIV risk reduction activities for the purposes of conception or otherwise and has been positively associated with partner HIV testing, increased care seeking, alleviation of anxiety, improved communication, and higher motivation to make plans for the future 
. Women who disclose their status may encounter reduced societal and familial expectations for childbearing 
but rising community awareness of the benefits of ART may increase pressure to conceive 
We observed that serostatus disclosure to the primary sexual partner was a positive and independent predictor of incident pregnancy, however, the effect was not observed until more than one year after ART initiation. Pregnancy intention was not measured in this study, however, the strong association with partner disclosure may suggest that these later pregnancies were wanted and/or planned, or discussed. Those pregnancies occurring in the first year may be highly influenced by the biological and behavioural changes observed with ART initiation and influencing fertility as described above. However, pregnancies occurring more than one-year after ART initiation might be less influenced by those changes and we may be observing a shift to more planned, intended pregnancies. The positive association between serostatus disclosure and pregnancy suggests a role for couples-based safe conception counselling in this population. More research is required to better understand this dynamic relationship.
Spouse HIV-status showed no association with pregnancy. Thirty-nine percent (39%) of women reported spouses of unknown or negative HIV-status, leaving those men at high risk for periconception or antepartum HIV-acquisition. Male partners play a large role in conception decisions and, if HIV-negative, risk HIV acquisition when seeking to conceive with an HIV-positive partner 
. Comprehensive reproductive counselling programs must include men.
Limitations of this study include use of self-report for pregnancy, which likely led to an underestimate of the true incidence. Pregnancies resulting in spontaneous abortion prior to detection and pregnancies that were electively terminated may not have been fully captured. Second, we did not have data on fertility intention, pregnancy desire, or contraceptive use, which would have implications for the most appropriate intervention. A higher proportion of unplanned pregnancies would emphasize the need for integrated family planning services including a range of contraceptive options for women initiating ART, who may experience restoration of fecundity. A higher proportion of ‘planned’ or ‘desired’ pregnancies would suggest a greater role for periconception risk reduction strategies to minimize HIV transmission risks. To address these limitations we have initiated a reproductive health study within this cohort to collect these data with the goal of understanding determinants of fertility intention, behaviour, and pregnancy among HIV-affected couples to inform the design of integrated bio-behavioural interventions to mitigate HIV-transmission risk among couples who intend to have children.
This study measured pregnancy incidence among HIV-positive women initiating ART and followed over a five-year period. Our findings that 9% were pregnant at ART initiation and that nearly one-third experience pregnancy subsequent to ART initiation highlight the need for integrated reproductive counselling and services that prevent unintended pregnancies and reduce periconception-related risks for HIV-positive women choosing to conceive.