Of the 850 women enrolled into the study, 822 (97%) had at least one followup visit between August 2009 and March 2011 and 734 (86%) completed study followup. Participants contributing to followup had a median of 6 visits over 12 months. The median time-on-ART at enrollment into the study was 13 months (interquartile range [IQR]: 5–24), and the median CD4 count was 320
L (IQR: 178–473). At enrollment, 429 women were on NVP, 350 on EFV and 43 on LPV/r-based regimens.
Overall 170 incident pregnancies were detected in 161 women (8 women were pregnant >1 time). Women contributed a total of 745 person-years (PY) at-risk for pregnancy; only time-at-risk for first pregnancy during study followup was included in the incidence analysis. Pregnancy incidence rates by regimen were 24.3/100
PY (95% Confidence Interval [CI]: 19.9–29.7) on NVP, 18.6/100
PY (95% CI: 14.2–24.2) on EFV and 18.8/100
PY (95% CI: 10.7–33.1) on LPV/r. Kaplan-Meier curves () demonstrate the one-year cumulative incidence of pregnancy across treatment arms. Incidence rates in the per-protocol analysis were slightly higher in women on NVP as compared to EFV throughout study followup (), although rates were not statistically significantly different between the two groups (log-rank NVP versus EFV: P
= 0.11). Because the research study intervened with patient care to refer women trying to conceive on EFV for regimen changes, the per-routine care analysis () illustrates pregnancy rates by regimen at study enrollment. In this analysis, differences in pregnancy incidence between the NVP and EFV arms were minimal (log-rank NVP versus EFV: P
Figure 1 Pregnancy incidence across antiretroviral therapy (ART) regimens according to (a) treatment at time of conception and (b) treatment had the study not intervened to refer participants for regimen change. NVP: Nevirapine; EFV: Efavirenz; PI: Protease Inhibitor (more ...)
Kaplan-Meier curves in assess the cumulative incidence of pregnancy on ART regimens during the 12 months of study followup, according to time on ART. Incidence across ART regimens was not statistically significantly different between EFV and NVP users (log-rank P = 0.09) and illustrates similar inferences to the previous analyses. also demonstrates, however, that the cumulative burden of pregnancy on EFV will be high over time, as women of reproductive age continue treatment on this regimen. In this analysis, 40% of women on EFV who had already been on ART for 3 years upon study entry, conceived on EFV during followup.
Figure 2 Cumulative incidence of pregnancy during study followup by years on antiretroviral therapy (ART); regimen arms represent time-varying treatment exposure during study followup. NVP: nevirapine-based regimen; EFV: efavirenz-based regimen; PI: boosted-protease (more ...)
Details of fetal exposure to EFV and fertility-related ART regimen substitutions are presented in . In total, 56 EFV conceptions were detected in 54 women. Twenty-five women with EFV conceptions received regimen changes during pregnancy; average time to regimen change amongst those actually changed was 6 weeks after conception [IQR: 4–8]. Nine pregnant women continued on EFV due to late detection (n = 4), clinic delays (n = 1), and indecision over pregnancy termination (n = 4). Thirty-four percent of EFV conceptions were terminated prior to regimen changes.
EFV conceptions and regimen substitutions.
Amongst sexually active women not trying to conceive, hormonal contraceptive use over followup was 32.9% in women on NVP, 25.7% on EFV, and 37.5% on LPV/r (P
< 0.01). Hormonal contraceptive use amongst women not trying to conceive was also lower in EFV versus non-EFV users at enrollment (EFV 28% versus non-EFV 35%, P
= 0.06). One EFV conception was attributed to an injectable contraceptive failure. Pregnancy incidence rates amongst hormonal contraception users on EFV versus NVP were 1.5/100
PY [95% CI: 0.2–10.9] and 7.1/100
PY [95% CI: 3.4–14.9], respectively; contraceptive failures were too infrequent and confidence intervals too wide for meaningful comparisons across hormonal contraceptive methods.
During followup, 96/350 (27%) women on EFV at enrollment had at least one visit in which they were trying to conceive on EFV, including fifteen women with planned pregnancies while on EFV-based regimens. All women trying to conceive on EFV were referred for regimen changes; however, records and patient reports suggested many providers would only substitute regimens after an established pregnancy to avoid unnecessary treatment changes. Thirty-two women received preventive regimen changes from EFV due to their fertility intentions; of these, 6 (19%) became pregnant during followup.
A total of 57 fertility-related regimen changes were made during the study due to either EFV conceptions or intention to conceive while on EFV. NVP was substituted for EFV 67% of the time and LPV/r 33% of the time. Women switched to LPV/r versus NVP had higher median CD4 counts (573 versus 257
< 0.01). Median viral load and acute liver damage (measured through alanine aminotransferase) were equivalent across groups (P
= 0.76 and P
Pregnancy outcomes for the 56 EFV conceptions were: live birth (n = 26), termination of pregnancy (n = 19), miscarriage (n = 9), and loss to followup (n = 2); no birth defects were detected in infants. Rates of pregnancy termination in EFV versus NVP users were 34% versus 23% (P = 0.15); rates of miscarriage between the two groups were 18% versus 16% (P = 0.71), respectively.