Background: We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program. Methods: Analysis 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. Findings: A 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). Conclusion: Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery. © 2012.
The MTCT-Plus Initiative provided support to 13 clinical programs in eight countries in sub-Saharan Africa (Cameroon, Côte d’Ivoire, Kenya, Mozambique, Rwanda, South Africa, Uganda, and Zambia) and in Thailand to implement HIV/AIDS care and treatment to families identified through PMTCT services [7]. Pregnant or recently postpartum women identified as HIV-infected (HIV+) in PMTCT programs were invited to enroll in the MTCT-Plus Initiative which was built upon existing services and provided HIV-infected women, their partners, and their children, holistic family care with unrestricted access to ART for eligible patients [8], [9]. ART eligibility was based on WHO and national guidelines in effect at the time. Prior to January 2005, criteria included CD4+ <200 cells/mm3, WHO stage 4, or CD4+ between 200 and 350 cells/mm3 and WHO stage 2 or 3 [1]. After January 2005, women with CD4+ between 200 and 350 cells/mm3 and stage 2 were no longer considered ART-eligible. ART-naïve pregnant women who were not eligible for ART, received an ARV prophylaxis regimen, had a CD4+ prior to or within 30 days of delivery ≥250 cells/mm3 and had at least one CD4+ after delivery were included in this analysis. Women receiving ART during pregnancy, or who had CD4+ <250 cells/mm3 at enrollment or who had no ARV prophylaxis or missing documentation of ARV prophylaxis were excluded. The MTCT-Plus Initiative procedures for enrollment and follow-up have been previously described [8]–[10]. In brief, pregnant women received CD4+ cell count at enrollment and maternal clinical and socio-demographic characteristics were recorded. HIV-infected women not eligible for ART were scheduled to attend follow-up visits every three months for the first six months following enrollment then every six months thereafter for clinical examination, WHO staging and CD4+ monitoring. MTCT-Plus Initiative sites followed local guidelines for PMTCT prophylactic regimens. Initially, most programs offered a sd-NVP regimen. By 2004, sites in Bangkok, Thailand, and Eldoret, Kenya, offered triple-drug ARV prophylaxis (tARVp) consisting of zidovudine (AZT) + lamivudine (3TC) + NVP or nelfinavir (NFV) prophylaxis during pregnancy. Over time most sites offered short-course (sc-ARVp) multidrug PMTCT regimens (antepartum AZT with or without 3TC + intrapartum sd-NVP). All ARV prophylaxis initiated antepartum or intrapartum was discontinued after delivery, as per WHO guidelines [1] including tARVp in women not eligible for ART. The primary outcome, CD4+ decline, was defined as: 1) the 12 and 24 month cumulative probability from delivery (time when ARV prophylaxis was discontinued) to decline in CD4+ to <200 cells/mm3 (2006 WHO recommended eligibility criteria for ART initiation) among women with enrollment CD4+ ≥250 cells/mm3; and 2) the 12 and 24 month cumulative probability from delivery to decline in CD4+ to 6 months since last scheduled visit), died, withdrew or were without an event at the date of their last clinical visit or March 31, 2008 when data collection ended. In addition, women who started ART after delivery were censored at the date ART was prescribed. The Log-Rank test was used to compare the probability of CD4+ decline to <200 cells/mm3 or <350 cells/mm3 between the three ARV prophylaxis groups (sd-NVP, sc-ARVp, and tARVp). We used Weibull regression models to identify risk factors for reaching the criteria for ART eligibility at 24 months. The following variables were considered: ARV prophylaxis regimen, age, CD4+ and WHO stage at enrollment. All factors associated with the outcomes at a p-value <0.25 were included in the multivariable analysis. Adjusted hazard ratios (aHR) and their 95% confidence interval (CI) are reported with two-sided p-values. The effect of program site was evaluated using Kaplan-Meier plots and associated Log-Rank tests independently for each ARV prophylaxis regimen. All analyses were performed in intent-to-treat and on-treatment population with SAS software version 9.2 (SAS Institute, Cary, NC, USA). The conduct of the MTCT-Plus Initiative as a service delivery program with data collection for monitoring and evaluation purposes was approved by Columbia University’s Institutional Review Board and local ethics review boards in each country where the study was implemented.