Virological and immunological impact of non-nucleoside reverse transcriptase inhibitor withdrawal in HIV-infected patients with multiple treatment failures
ABSTRACT No significant changes in viral load and CD4 cell count were observed 2-4 weeks after the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTI) from the current therapy of patients exhibiting resistance mutations to this class of drugs. The data suggest that in the presence of specific resistance mutations NNRTIexert no residual antiretroviral activity and could be withdrawn without viral rebound.
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ABSTRACT: In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.Clinical Infectious Diseases 01/2014; 58(7). DOI:10.1093/cid/cit933 · 9.42 Impact Factor
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ABSTRACT: To describe the prevalence of specific protease inhibitor (PI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations and the relationship between the presence of these mutations and immunologic outcomes following PI/NNRTI initiation among a cohort of HIV-1-infected women. Viral genotypic resistance testing was done for 366 women enrolled in the Women's Interagency HIV Study at the visit immediately prior to 1st reported use of PI or NNRTI (baseline) and at the visit approximately 1 year after PI/NNRTI initiation. We modeled the changes in CD4+ T-cell counts and HIV RNA levels approximately 1 year after therapy initiation as a function of baseline and follow-up markers, type of antiretroviral therapy used, and resistance mutations. At baseline, 52% of women showed only nucleoside reverse transcriptase inhibitor (NRTI) mutations, 38% showed no mutations, and 10% showed PI or NNRTI mutations. Only 40% of women showed viral response (HIV-1 RNA < or = 80 copies/mL) 1 year after initiating a PI or NNRTI. Among those without a viral response, 54% developed PI or NNRTI mutations. NNRTI (among those with baseline NRTI mutations) and PI resistance mutations were associated with better CD4+ cell count changes (mean increase of 118 cells/mm3 and 64 cells/mm3, respectively, as compared with viral nonresponders with no PI or NNRTI mutations). In this population-based cohort, virologic failure with PI or NNRTI resistance was common. Viremia with these resistance mutations was associated with preserved CD4+ T-cell count responses, providing evidence of reduced virulence or viral fitness.JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2006; 41(1):68-74. DOI:10.1097/01.qai.0000174652.40782.4e · 4.39 Impact Factor
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ABSTRACT: Despite dramatic declines in HIV-associated morbidity and mortality as a result of highly active antiretroviral therapy, management of heavily treatment-experienced patients remains complex and challenging. Treatment response rates with subsequent antiretroviral regimens are lower than with initial antiretroviral therapy. Additionally, increased mortality has been associated with multidrug-resistant HIV. We review data relevant to management of such patients and offer a systematic approach to constructing a salvage antiretroviral regimen.The Lancet Infectious Diseases 09/2006; 6(8):496-507. DOI:10.1016/S1473-3099(06)70550-3 · 19.45 Impact Factor