Browsing by Author "Chi, Benjamin H."

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    Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure
    (New England Journal of Medicine, 2010) Palumbo, Paul; Lindsey, Jane C.; Hughes, Michael D.; Cotton, Mark F.; Bobat, Raziya; Meyers, Tammy; Dangarembizi, Mutsawashe Bwakura; Chi, Benjamin H.; Musoke, Philippa; Kamthunzi, Portia; Schimana, Werner; Purdue, Lynette; Eshleman, Susan H.; Abrams, Elaine J.; Millar, Linda; Petzold, Elizabeth; Mofenson, Lynne M.; Philippe, Patrick Jean; Violari, Avy
    Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events.Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151. opens in new tab.)
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    A Cluster Randomized Trial of Routine HIV-1 Viral Load Monitoring in Zambia: Study Design, Implementation, and Baseline Cohort Characteristics
    (PLoS One, 2010) Koethe, John R.; Westfall, Andrew O.; Luhanga, Dora K.; Clark, Gina M.; Goldman, Jason D.; Mulenga, Priscilla L.; Cantrell, Ronald A.; Chi, Benjamin H.; Zulu, Isaac; Saag, Michael S.; Stringer, Jeffrey S. A.
    The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.
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    Risk Factors for Adverse Birth Outcomes in the PROMISE 1077BF/1077FF Trial
    (Journal of acquired immune deficiency syndromes, 2019) Sebikari, Dorothy; Farhad, Mona; Fenton, Terry; Owor, Maxensia; Stringer, Jeffrey S. A.; Qin, Min; Chakhtoura, Nahida; Chi, Benjamin H.; Saidi, Friday; Nevrekar, Neetal; Violari, Avy; Chipato, Tsungai; McIntyre, James A.; Moodley, Dhayendre; Taha, Taha E.; Theron, Gerhard; Glenn Fowler, Mary
    In the multi-country PROMISE 1077BF trial, the risk of low birth weight (LBW; <2500g) and preterm delivery (PTD; <37 weeks) was higher among women initiating a protease inhibitor (PI)-based antiretroviral treatment (ART) regimen than in those receiving ZDV alone. Among those assigned to a PI regimen, tenofovir/emtricitibine was associated with the more severe outcomes of very LBW (VLBW; <1500g) and very PTD (VPTD; <34 weeks) compared to zidovudine/lamivudine. Methods: We used multivariate logistic regression to further explore treatment findings, taking into account demographic baseline clinical and post-entry obstetrical factors. We evaluated individual adverse outcomes and composites that included stillbirth and early loss/spontaneous abortion. Results: Among 3333 women delivering at least one live infant, median maternal age at enrollment was 26 years; 661 (20%) were primiparous, and 110 (3.3%) reported at least one prior PTD. Seventeen percent of newborns were LBW, 1% were VLBW, 17% had PTD, and 3% VPTD. Treatment allocation remained strongly associated with multiple adverse outcomes after controlling for other risk factors with both ART regimens exhibiting increased risk relative to ZDV alone. Other risk factors remaining significant in at least one of the multivariate models included: country, gestational age at entry, maternal age, maternal BMI, prior PTD, history of alcohol use, baseline HIV viral titer, multiple gestation and several obstetric risk factors. Conclusion: ART effects on adverse pregnancy outcomes reported in the randomized PROMISE trial remained strongly significant even after controlling for demographic, baseline clinical and obstetrical risk factors, which were also associated with these outcomes.