We describe changes in HIV-1 viral load, CD4+ T cell percentage, and incidence of drug resistance and factors associated with drug resistance for 134 children receiving antiretroviral therapy (ART) for approximately 1 year in Abidjan. Between August 1998 and September 2003, ART was initiated for 395 HIV-infected children ages 0-15 years in the Côte d'Ivoire national drug access initiative. All 1-year samples with detectable HIV RNA >1000 copies/ml were tested for HIV-1 drug resistance and changes in viral load and CD4+ T cell counts were also determined. At treatment initiation, 80% of children had CD4+ T cell percentages <15% and a median viral RNA load of 5.6 log copies/ml. The median age at treatment initiation was 7 years with only 25% of patients less than 4 years of age. Of the 134 children receiving therapy, 72 (54%) had undetectable viral load. The estimated 1-year viral load decline was 1.9 log10 copies/ml and the CD4+ T cell percentage increase was 10.9%. The estimated 1-year cumulative probability for developing any class of drug resistance was 0.44 (95% CI, 0.35, 0.53). In a multivariate analysis, the magnitude of virologic response to therapy was inversely associated with development of drug resistance. Children with less CD4+ T cell rise from baseline values and the use of dual therapy were also associated with the development of drug resistance. Guidelines are needed for the treatment of pediatric HIV infection in Africa in order to minimize the occurrence of drug resistance and enhance better virologic, immunologic, and clinical outcomes.
As antiretroviral therapy continues to scale-up in developing countries, there is concern that high levels of HIV drug resistance to antiretroviral drugs will occur. Here we describe rates of emergence of HIV-1 drug resistance and factors associated with their occurrence among adults who received antiretroviral therapy (ART) for >1 year through the Côte d'Ivoire national drug access program from 1998 to 2003. To detect genotypic drug resistance, we sequenced all 1- and 2-year specimens with detectable HIV RNA viral load. To assess factors associated with emerging drug resistance, we used log normal regression with interval censoring, including covariates in the model for self-reported drug adherence, CD4 cell count, and HIV viral load at therapy initiation, and observed changes in these measures, type of prescribed ART drugs, diagnoses of opportunistic illness, and demographic characteristics. An estimated 14.2% [95% confidence limits (CL) 11.7, 16.9] and 26.6% (95% CL 22.7, 30.8) of patients developed primary drug-resistant mutations within 1 year and 2 years after initiation of therapy, respectively. Factors associated with drug resistance included drug nonadherence, partial or lack of viral suppression, higher viral load or lower CD4 at initiation of therapy, and initiation of ART with what is now considered substandard dual combination therapy. Our results demonstrate the need to strengthen adherence and continuity in treatment programs in order to avoid interruption of ART drugs. Treatment programs should pay attention to indicators of emerging drug resistance: incomplete or lesser decreases in viral load or increases in CD4 cell counts following initiation of therapy, and the occurrence of AIDS opportunistic illnesses.
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