Browsing by Author "Sheneberger, Robert"

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    Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.
    (2011-Dec-15) Chi, Benjamin H.; Mwango, Albert; Giganti, Mark J.; Sikazwe, Izukanji ; Moyo, Crispin; Schuttner, Linnaea; Mulenga, Lloyd B.; Bolton-Moore, Carolyn; Chintu, Namwinga T.; Sheneberger, Robert; Stringer, Elizabeth M.; Stringer, Jeffrey S.
    BACKGROUND: Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP). METHODS: We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP. RESULTS: Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome. CONCLUSION: TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.
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    Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.
    (2010-May-01) Chi, Benjamin H.; Mwango, Albert; Giganti, Mark; Mulenga, Lloyd B.; Tambatamba-Chapula, Bushimbwa ; Reid, Stewart E.; Bolton-Moore, Carolyn; Chintu, Namwinga ; Mulenga, Priscilla L.; Stringer, Elizabeth M.; Sheneberger, Robert; Mwaba, Peter; Stringer, Jeffrey S.
    BACKGROUND: In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. METHODS: We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. RESULTS: Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. CONCLUSIONS: TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.