What will it take to eliminate pediatric HIV? Reaching WHO target rates of mother-to-child HIV transmission in Zimbabwe: a model-based analysis

Abstract

Background: The World Health Organization (WHO) has called for the "virtual elimination" of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe.

Methods and findings: We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' "Option A" (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO "Option B" (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning. The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%-7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%.

Conclusions: Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the "virtual elimination" of pediatric HIV in Zimbabwe. Please see later in the article for the Editors' Summary.

Figure 1. Two dimensions for potential improvements in PMTCT in Zimbabwe.

This figure shows the “two dimensions” in which PMTCT services can be improved. First, along the vertical arrow, PMTCT programs can transition to more intensive drug regimens (i.e., from sdNVP to Option A to Option B). Second, along the horizontal arrow, programs can undertake interventions to improve “uptake” of PMTCT services, defined as the proportion of pregnant, HIV-infected women who receive and adhere to ARVs for PMTCT, for example, from 36% in 2008 to 56% in 2009, and perhaps to 80% or 95% with future scale-up effort. Within the horizontal arrow are depicted the three “domains” of uptake examined in these analyses: care and testing, drug availability, or retention. sdNVP represents the current National PMTCT Program, based largely on sdNVP; “Option A” and “Option B” are the WHO 2010 PMTCT guideline-recommended regimens, as defined in the text and Text S1.

Figure 2. Key parameters determining MTCT risk.

Tornado diagram summarizing the results of key one-way sensitivity analyses. Model parameters are on the vertical axis. For each parameter, the value used in the base-case analysis is listed in parentheses, followed by the range examined in sensitivity analysis. For example, the “regimen” provided for PMTCT is varied from Option B (lowest MTCT risk with all other parameters held constant), through Option A (base-case MTCT risk), to sdNVP (highest MTCT risk). The horizontal axis represents projected MTCT risk by the time of weaning. The solid vertical line represents transmission risk (14.4%) at the base-case set of parameters: 56% uptake, mean published MTCT risks, 36% of mothers with CD4<350/µl, breastfeeding duration of 12 mo, and the WHO “Option A” regimen. The dashed vertical line represents the 5% MTCT target of “virtual elimination” expressed by international HIV/AIDS agencies including WHO and the Joint United Nations Programme on HIV/AIDS. ARV prophylaxis in the Option A and Option B regimens is assumed to continue throughout the duration of breastfeeding.

Figure 3. Combinations of parameters needed to achieve MTCT risks<5%, 5%–10%, and >10%.

Each horizontal block represents results for a specific drug regimen: sdNVP (top), Option A (middle), and Option B (bottom). Within each block, four levels of uptake are depicted across the top horizontal axis: 56% uptake (current estimated uptake in Zimbabwe), 80% uptake (the WHO target), 95% uptake (reported in neighboring Botswana), and 100% uptake (to reflect maximum biologic efficacy of each regimen). The vertical axis illustrates three durations of breastfeeding (BF) for each modeled PMTCT regimen: 18 mo (median in Zimbabwe), 12 mo (concordant with 2010 WHO infant feeding guidelines), and no breastfeeding; ARV prophylaxis in the Option A and Option B regimens is assumed to continue throughout the duration of breastfeeding. The lower horizontal axis shows three categories of published MTCT risks for each drug regimen, including the lowest published risks, the average of published risks (the base-case parameters), and the highest published risks. The percentage in each cell reflects the MTCT risk associated with each set of parameters, and cells are color-coded to reflect broad categories of transmission. Red-colored cells indicate MTCT risks>10%, yellow-colored cells indicate MTCT risks between 5% and 10%, and green-colored cells indicate MTCT risks<5%.