Men were significantly older than women irrespective of pregnancy status [median age 34 (IQR 31–39) vs. 29 years (IQR 26–33), P < 0.001] and had heavier weight [median 61 (IQR 55–67) vs. 57 kg (IQR 50–65), P < 0.001] than nonpregnant women. Overall, men had significantly higher rates of employment outside the home than women (72 vs. 29%, P < 0.001).
Antiretroviral regimens included NVP for 2012 (90%) patients, with lamivudine (3TC) and either ZDV or stavudine (d4T). An additional 189 (9%) patients, including two pregnant women in their third trimester, started efavirenz with 3TC and either ZDV or d4T. Initial ART regimens were similar for men, pregnant women, and nonpregnant women.
Predicted CD4 cell count response did not vary by WHO stage at baseline, but did vary by country. Participants from sites in Cote d'Ivoire had the greatest increase in CD4 cell count at 6 months and at every time point thereafter.
As of January 2007, 1902 (85%) of the 2229 patients who initiated ART were alive and in active follow-up. Over 4193 person-years of follow-up, 77 (3.5%) patients were known to have died (1.8 per 100 person-years) and 192 (8.6%) patients were LTF (4.6 per 100 person-years). An additional 58 patients (2.6%) voluntarily withdrew from the program (1.4 per 100 person-years) due to change in place of residence (n = 17), seeking care elsewhere (n = 24), refusal of further participation (n = 8), inability to adhere to ART or the visit schedule (n = 6), or other reasons (n = 3). The mortality rates for pregnant women (17 deaths, 1.5 per 100 person-years), nonpregnant women (34 deaths, 1.7 per 100 person-years), and men (26 deaths, 2.4 per 100 person-years) were similar (P = 0.18). Mortality was associated with lower baseline CD4+ cell count (P < 0.001), higher baseline WHO stage (P < 0.001), and country of enrollment (P < 0.001), but not sex or pregnancy status.
Kaplan–Meier probability of program retention (death, LTF and withdrawal) was 0.85 overall, and was similar across sex and pregnancy groups: 0.82 for pregnant women, 0.87 for nonpregnant women, and 0.86 for males (log rank P = 0.10). Poorer program retention was associated with higher WHO stage (III or IV) at baseline (P < 0.001), but not CD4+ cell count.
This study is one of the first to report on immunologic outcomes, mortality, and program retention for ART-eligible women starting ART during pregnancy. We demonstrate a robust CD4+ cell count response during the first 2.5 years of treatment comparable to, if not better than, nonpregnant adults. Furthermore, we report low mortality and high retention for all patients initiating ART. These findings are particularly important as national PMTCT programs evolve to prioritize the identification and treatment of eligible pregnant women with therapeutic ART . The MTCT-Plus Initiative has previously documented the benefit of ART use during pregnancy in reducing the risk of MTCT .
We noted lower mortality rates in our population of adults initiating ART as compared with other studies in the literature. Most programs have reported higher mortality rates, 5.5–9.7 per 100 person-years of follow-up, during the first few months of treatment attributed to the highly advanced disease status of many of the patients [16,55,56]. In comparison, there were only 17 documented deaths among women initiating ART during pregnancy (1.5 per 100 person-years), 34 deaths among nonpregnant women (1.7 per 100 person-years) and 26 deaths among men (2.4 per 100 person-years) in this cohort. Overall retention in care was high: 82% for pregnant women, 86% for men, and 87% of nonpregnant women at 30 months of follow-up. The healthier status of MTCT-Plus patients likely contributed to lower mortality risk and high retention rates, as it has been noted that a significant percentage of patients LTF in most cohort studies [30–32] have died. In addition, the MTCT-Plus model of care emphasized psychosocial support and adherence to care and treatment as critical components of the program. Sites supported through the MTCT-Plus Initiative were relatively well resourced with high provider–patient ratios and access to a wider range of supportive services.
This study has several strengths. Sites followed standardized MTCT-Plus protocols, received standardized MTCT-Plus training prior to start-up, and used standardized data collection forms. Furthermore, most patients initiated NNRTI-based ART, primarily with NVP, resulting in a relatively homogenous treatment population.
However, the study had several limitations. The data were derived from a clinical care program rather than a research study. Thus, there may have been variability across the program CD4+ cell counts, as measurements were done in local laboratories.
In summary, we have demonstrated that pregnant women as well as nonpregnant women and male partners who initiated first-line ART had excellent CD4+ cell count response and high retention in care during the first 2.5 years of follow-up. These findings lend support to the WHO recommendations for RLCs, which suggest initiation of ART in pregnant women if they are eligible for treatment .
Funding for the MTCT-Plus Initiative was provided by the Bill and Melinda Gates Foundation, the William and Flora Hewlett Foundation, the Robert Wood Johnson Foundation, the Henry J. Kaiser Family Foundation, the John D. and Catherine T. MacArthur Foundation, the David and Lucille Packard Foundation, the Rockefeller Foundation, and the Starr Foundation.
MTCT Plus Initiative: ACONDA FSU and Abobo clinics, Cote d'Ivoire (Dr Siaka Toure); Moi University College of Health Sciences Clinics, Kenya (Drs Robert Eintez and Joseph Mamlin); Nyanza Provincial General Hospital Clinic, Kenya (Dr Juliana Otieno); Treatment and Research AIDS Center, Rwanda (Dr Anita Assimwe); Cato Manor Clinic of UKZN, South Africa (Dr Anna Coutsoudous); Langa Health Clinic of Western Cape, South Africa (Dr Ivan Toms); Perinatal HIV Research Unit of University of Witswatersrand, South Africa (Dr James McIntyre); Thai Red Cross Clinic, Thailand (Dr Praphan Phanuphak); MU-JHU Cares Clinic, Uganda (Dr Philippa Musoke); St. Francis Hospital Clinic, Uganda (Dr Pius Okong); and Mtendere and Chelstone Health Clinics, Zambia (Dr Elizabeth Stringer).
P.T. was the primary writer of the manuscript and led the analysis. M.K. was the analyst/statistician. She reviewed and edited the manuscript. R.C. revised drafts and gave input throughout the analytic phase. W.E.-S. edited the manuscript and gave input throughout the writing process. L.M. edited the manuscript and gave specific input into issues of HIV treatment during pregnancy. D.N. advised during analysis. E.A. gave extensive editorial support and advised throughout the analysis.
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