Maternal CD4+ Cell Count Decline after Interruption of Antiretroviral Prophylaxis for the Prevention of Mother-to-Child Transmission of HIV

Abstract

BackgroundWe evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program.MethodsAnalysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm3 at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm3 or <200 cells/mm3 at 24 months. Weibull regression was used for multivariable analysis.FindingsA total of 1,393 women with enrollment CD4+ ≥250 cells/mm3 initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23–30), median CD4+ was 469 cells/mm3 (IQR: 363–613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm3 was 12% (95% CI: 10–14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm3 was 28%; (95% CI: 25–32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm3: 46% (CD4+400–499 cells/mm3) vs. 19% (CD4+ ≥500 cells/mm3). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5–3.2, p<0.0001).ConclusionDecline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

HIV Disease Progression in the First Year After Delivery Among African Women Followed in the HPTN 046 Clinical Trial

“…These findings are similar to data from the multi-country MTCT-Plus Initiative, which found that women stopping a variety of ARV regimens for prevention of perinatal transmission had a 46% risk of dropping below 350 cells/uL by 24 months postpartum when the initial CD4+ cell count during pregnancy was 400–499 cells/uL. 10 A study from Haiti found that women stopping antiretroviral prophylaxis at delivery with a CD4+ lymphocyte count between 350 and 499 cells/uL dropped to the threshold of 350 cells/uL requiring therapy at a median of 19 months after delivery compared to a median of 71 months to reach this threshold among women with CD4+ cell counts at or above 500 cells/uL at delivery. 11 These data are also consistent with a study from Brazil, which showed that among women discontinuing ARV agents after delivery, the group with levels between 250–500 cells/uL had a risk of progression to stage II or III events that was 2.5 times higher than women with CD4+ counts above 500 cells/uL.…”

“…These results are consistent with data from the MTCT-Plus Initiative which demonstrated that 18.5% of women with initial CD4+ cell counts above 500 cells/uL during pregnancy progressed to counts below 350 cells/uL by 24 months after delivery. 10 The group of women with CD4+ cell counts above 550 cells/uL would be expected to have a low risk of disease progression even with discontinuation of ARVs after pregnancy and breastfeeding, so could discontinue therapy if desired. These findings underscore the utility of CD4+ lymphocyte testing and suggest that in this group of women, more data are needed regarding the risks and benefits of continuing ARVs after risk of mother-to-child transmission of HIV has passed.…”

The incremental cost of switching from Option B to Option B+ for the prevention of mother-to-child transmission of HIV

“…[18][19][20][21] In our main analyses we examined the cost per woman (individual analysis) and the cost per cohort of women (cohort analysis). We also conducted sensitivity analyses to examine the effect on costs of varying ARV prices and postpartum rates of decline in CD4+ cell count.…”

Frihet i en pille?

“…Most of these studies used the historical threshold for ART initiation of CD4 count below 350 cells/mm 3 , and in several cases mothers were receiving ARV prophylaxis rather than ART, but all showed a gradual decline in immune function after ARV drugs were stopped. Using the time frame of six months after discontinuation, 6-20% of women with a baseline CD4 count below 500 cells/mm 3 had become eligible, whereas only 1.5% of women became eligible if the baseline CD4 was above 500 cells/mm 3 (101,102). A lower baseline CD4 count was also associated with a 2.5-fold higher risk of WHO stage 2 or 3 clinical events (103).…”