Person: Ciaranello, Andrea
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Publication What Will it Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis
(Public Library of Science, 2012) Perez, Freddy; Keatinge, Jo; Park, Ji-Eun; Engelsmann, Barbara; Maruva, Matthews; Dabis, Francois; Chu, Jennifer; Rusibamayila, Asinath; Mushavi, Angela; Walensky, Rochelle; Ciaranello, Andrea; Freedberg, KennethBackground: 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/(\mu)l; 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.
Publication Cost-Effectiveness of World Health Organization 2010 Guidelines for Prevention of Mother-to-Child HIV Transmission in Zimbabwe
(Oxford University Press, 2012) Perez, Freddy; Engelsmann, Barbara; Mushavi, Angela; Rusibamayila, Asinath; Keatinge, Jo; Park, Ji-Eun; Maruva, Matthews; Wood, Robin; Dabis, Francois; Ciaranello, Andrea; Walensky, Rochelle; Cerda, Rodrigo; Freedberg, KennethBackground. In 2010, the World Health Organization (WHO) released revised guidelines for prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). We projected clinical impacts, costs, and cost-effectiveness of WHO-recommended PMTCT strategies in Zimbabwe. Methods. We used Zimbabwean data in a validated computer model to simulate a cohort of pregnant, HIV-infected women (mean age, 24 years; mean CD4 count, 451 cells/µL; subsequent 18 months of breastfeeding). We simulated guideline-concordant care for 4 PMTCT regimens: single-dose nevirapine (sdNVP); WHO-recommended Option A, WHO-recommended Option B, and Option B+ (lifelong maternal 3-drug antiretroviral therapy regardless of CD4). Outcomes included maternal and infant life expectancy (LE) and lifetime healthcare costs (2008 US dollars [USD]). Incremental cost-effectiveness ratios (ICERs, in USD per year of life saved [YLS]) were calculated from combined (maternal + infant) discounted costs and LE. Results. Replacing sdNVP with Option A increased combined maternal and infant LE from 36.97 to 37.89 years and would reduce lifetime costs from $5760 to $5710 per mother–infant pair. Compared with Option A, Option B further improved LE (38.32 years), and saved money within 4 years after delivery ($5630 per mother–infant pair). Option B+ (LE, 39.04 years; lifetime cost, $6620 per mother–infant pair) improved maternal and infant health, with an ICER of $1370 per YLS compared with Option B. Conclusions. Replacing sdNVP with Option A or Option B will improve maternal and infant outcomes and save money; Option B increases health benefits and decreases costs compared with Option A. Option B+ further improves maternal outcomes, with an ICER (compared with Option B) similar to many current HIV-related healthcare interventions.
Publication Optimal breastfeeding durations for HIV‐exposed infants: the impact of maternal ART use, infant mortality and replacement feeding risk
(John Wiley and Sons Inc., 2018) Mallampati, Divya; MacLean, Rachel L; Shapiro, Roger; Dabis, Francois; Engelsmann, Barbara; Freedberg, Kenneth; Leroy, Valeriane; Lockman, Shahin; Walensky, Rochelle; Rollins, Nigel; Ciaranello, AndreaAbstract Introduction: In 2010, the WHO recommended women living with HIV breastfeed for 12 months while taking antiretroviral therapy (ART) to balance breastfeeding benefits against HIV transmission risks. To inform the 2016 WHO guidelines, we updated prior research on the impact of breastfeeding duration on HIV‐free infant survival (HFS) by incorporating maternal ART duration, infant/child mortality and mother‐to‐child transmission data. Methods: Using the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐Infant model, we simulated the impact of breastfeeding duration on 24‐month HFS among HIV‐exposed, uninfected infants. We defined “optimal” breastfeeding durations as those maximizing 24‐month HFS. We varied maternal ART duration, mortality rates among breastfed infants/children, and relative risk of mortality associated with replacement feeding (“RRRF”), modelled as a multiplier on all‐cause mortality for replacement‐fed infants/children (range: 1 [no additional risk] to 6). The base‐case simulated RRRF = 3, median infant mortality, and 24‐month maternal ART duration. Results: In the base‐case, HFS ranged from 83.1% (no breastfeeding) to 90.2% (12‐months breastfeeding). Optimal breastfeeding durations increased with higher RRRF values and longer maternal ART durations, but did not change substantially with variation in infant mortality rates. Optimal breastfeeding durations often exceeded the previous WHO recommendation of 12 months. Conclusions: In settings with high RRRF and long maternal ART durations, HFS is maximized when mothers breastfeed longer than the previously‐recommended 12 months. In settings with low RRRF or short maternal ART durations, shorter breastfeeding durations optimize HFS. If mothers are supported to use ART for longer periods of time, it is possible to reduce transmission risks and gain the benefits of longer breastfeeding durations.