At the time the HIV treatment program began, 418 HIV-infected women were still in active follow-up as part of the infant feeding trial and 335 (80.1%) agreed to be screened for ART eligibility. Factors associated with electing to be screened for ART included higher parity, survival of index child, clinic A, fewer missed study visits, clinical stage ≥2 and disclosure of HIV status (data not shown). Of those who agreed to be screened, 162 (48.4%) met eligibility criteria and 131 (80.9%) initiated therapy. An additional 199 women not in active follow-up at the time of program roll-out could be located and agreed to be screened, 107 (53.8%) met eligibility criteria, and 86 (80.4%) initiated therapy. Of the 52 women who were eligible but did not begin therapy, 5 died, 4 had treatment delayed due to tuberculosis treatment, 3 received ART elsewhere and the others actively refused or passively did not return for visits ().
Flow chart showing the disposition of study participants over the course of the study.
Mortality among HIV-infected women in our cohort was reduced by more than half (relative hazard (RH) = 0.46 95% CI: 0.23–0.91 p=0.03) in the time period once ART became available. Of 872 HIV-infected women in the cohort surviving and still in follow-up 6 weeks after delivery, 53 died before 24 months post-delivery in the period prior to the availability of ART and 11 died in the period after. The probability of death by 12 months was 4.3% and by 24 months 10.3% in the pre-ART era. Reduction in mortality associated with access to ART remained significant (RH=0.47 95% CI: 0.23–0.93) after adjustment for CD4 count (RH=0.57 per each 100 cells/mL increase 95% CI: 0.45–0.71) and viral load (RH 2.14 per each log10 copies/mL increase 95% CI: 1.36–3.37) measured during pregnancy in a multivariate Cox model.
To investigate whether the length of time that had elapsed since SDNVP would influence ART outcomes, we focused on 217 women who initiated ART. Of these, 22 were excluded because they did not receive SDNVP (6 because ART was initiated during pregnancy and 16 because SDNVP was not used in the index pregnancy due to miscarriage , stillbirth  or noncompliance ). Of the remaining 195 women, 9 (4.6%) stopped all therapy, 14 (7.2%) were lost to follow-up and 7 (3.6%) died before 6 months post-therapy. Of 165 women who were not known to have discontinued ART and who were followed to 6 months, the median time between SDNVP and ART initiation was 23 months (min 3 weeks, max 54 months, inter-quartile range 15 to 32 months). Most women (54.5%) initiated therapy with nevirapine, lamivudine and zidovudine, 40.6% with nevirapine, lamivudine and stavudine, and 4.8% with efavirenz, lamivudine and either zidovudine or stavudine.
Of 161 SDNVP-exposed women still on treatment at 6 months, 70.8% achieved a viral load <400 copies/ml and 40.4% a viral load <50 copies/ml. Four had no sample stored for viral load testing. The longer the duration of time between SDNVP exposure and treatment initiation, the greater the percentage who achieved viral suppression. Of 8 women exposed to SDNVP within 6 months of starting therapy, only 3 (37.5%) achieved a viral load of <400 copies/ml by 6 months post-therapy, compared to 59.1% of 22 women who started within 6–12 months post-exposure, 72.1 % of 61 who started within 12–24 months, and 77.1% of 70 who started more than 24 months after exposure (p=0.01). The patterns were similar using different cut-offs to define suppression ().
Percentage of women who had viral loads of <50 copies/ml, 50–399 copies/ml, 400–999 copies/ml and ≥1000 copies/ml at 6 months post-therapy initiation by number of months since single-dose nevirapine exposure.
Other factors found to be significantly associated with better viral suppression were being a non-transmitter (child uninfected 76.9% suppressed; child infected 59.7% suppressed p=0.02) and being unemployed (employed 57.1% suppressed; unemployed 78.1% suppressed p=0.005). The association between a longer time since SDNVP and better viral suppression remained significant after adjusting for transmission and employment status. The association between longer time since SDNVP and response to therapy was attenuated and became non-significant if adjusted for pre-treatment viral load, although this latter factor was not significantly associated with virologic response. The association between time since SDNVP exposure and viral suppression was strongest among those whose viral load during the pregnancy in which SDNVP was received was ≥100,000 copies/ml (SDNVP exposure occurred ≤ 12 months earlier 35.3% suppressed; vs. > 12 months earlier 72.9% suppressed, p=0.006), and was not apparent among those with a viral load < 100,000 copies/ml (SDNVP exposure occurred ≤ 12 months earlier 75.0% suppressed; vs. > 12 months earlier 75.9% suppressed, p>0.1), but the interaction term was not significant (p=0.09).
With HIV treatment programs now in place, women should be screened for ART during pregnancy. Based on symptom checklists, examinations and CD4 count data collected during pregnancy on the 1378 women enrolled, 38.3% of women should have started ART during pregnancy (i.e. their CD4 counts were <200 or <350 with stage III conditions). Mortality in women who met ART eligibility criteria was high with 23.7% mortality by 24 months (11.9% by 12 months) in the era before ART became available. Among those not yet eligible for ART during pregnancy, only 6.0% met eligibility criteria when re-tested 12 months after delivery in the era before ART became available. If only CD4 counts are used to determine ART eligibility, 55.8% had a CD4 count <350 during pregnancy and 11.8% of those with CD4 counts above 350 during their pregnancy had CD4 count <350 when re-tested 12 months after delivery.