Journal Articles (Medical School)

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Browsing Journal Articles (Medical School) by Subject "Antiretroviral"

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    Development of Phenotypic and Genotypic Resistance to Antiretroviral Therapy in the UNAIDS HIV Drug Access Initiative – Uganda
    (Wolters Kluwer Health, Inc., 2003-07) Weidlea, J. Paul; Downingb, Robert; Sozic, Catherine; Mwebaze, Raymond; Rukundo, Gideon; Malamba, Samuel; Respessa, Richard; Hertogsf, Kurt; Larderg, Brendan; Ochola, Dorothy; Mermin, Jonathan; Badara Sambk, Badara; Lackritz, Eve
    Objective: We describe phenotypic drug resistance, response to therapy, and geno-typic mutations among HIV-infected patients in Uganda taking antiretroviral medica-tions for ≥ 90 days who had a viral load ≥ 1000 copies/ml. Methods: HIV-1 group and subtype, virologic and immunologic responses to anti-retroviral therapy, phenotypic resistance to antiretroviral drugs, and associated geno-typic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse tran-scriptase inhibitors (NRTIs) or highly active antiretroviral therapy (HAART). Results: All HIV identified was HIV-1, group M, subtypes A, C, and D. Sixty-one (65%) of 94 patients with a phenotypic resistance result had evidence of phenotypic resistance including resistance to a NRTI for 51 of 92 (55%) taking NRTIs, to a non-nucleoside reverse transcriptase inhibitor (NNRTI) for nine of 16 (56%) taking NNRTIs, and to a protease inhibitor (PI) for eight of 37 (22%) taking PIs. At the time of the first specimen with resistance, the median change from baseline viral load was –0.56 log copies/ml [interquartile range (IQR), –1.47 to +0.29] and CD4+ cell count was +35 × 106 cells/l (IQR, –18 to +87). Genotypic resistance mutations, matched with phenotypic resistance assay results and drug history, were generally consistent with those seen for HIV-1, group M, subtype B infections in industrialized countries. Conclusion: Initial phenotypic resistance and corresponding genotypic mutations among patients treated in Uganda were similar to those with subtype B infections in North America and Europe. These data support policies that promote the use of HAART regimens against HIV-1, group M, non-B subtypes in a manner consistent with that used for subtype B infections.
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    Therapeutic Responses to AZT 1 3TC 1 EFV in Advanced Antiretroviral Naive HIV Type 1-Infected Ugandan Patients
    (Mary Ann Liebert, Inc., 2004-07-05) Kebba, Anthony; Atwine, Diana; Mwebaze, Raymond; Kityo, Cissy; Nakityo, Rose; Mulenyi, Peter
    Convenient, non-food-dependent dosing, low tablet volume, and relatively low cost have made nonnucleoside reverse transcriptase inhibitors a first choice for both clinicians and patients in Uganda. Concerns exist as to their efficacy in patients with viral loads (VL) above 100,000 copies/ml, a feature common to about 75% of HIV-1-infected patients presenting at the Joint Clinical Research Center (JCRC) in Uganda. Furthermore, there are few data on the response to such therapy of non-B subtypes, A and D, predominant in Uganda. Presented here is a retrospective analysis of therapeutic responses in 11 antiretroviral (ARV) naïve HIV-1-infected Ugandan patients who had been initiated on zidovudine (AZT), lamivudine (3TC), and efavirenz (EFV). Laboratory assessments subsequent to initiation of ARV therapy, done at 11.6 ± 3.9 weeks and 30.6 ± 5.9 weeks, showed 88.9 and 71.4% patients achieved undetectable viral load, respectively. Virological suppression to below detection occurred in 85.7% of patients at 11.6 weeks despite baseline VL ≥ 100,000 copies/ml. At 31 weeks there was a median increment of +183 cells/mm3 in CD4+ T lymphocytes. These findings reflect significant efficacy in the use of AZT + 3TC + EFV in advanced ARV naive non-B subtype HIV-1-infected patients. The therapeutic responses were comparable to those previously described in the western world.