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Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.

ABSTRACT: INTRODUCTION:The HIV-1 epidemic in African countries is largely due to non-B HIV-1 subtypes. Patterns and frequency of antiretroviral drug resistance mutations observed in these countries may differ from those in the developed world, where HIV-1 subtype B predominates. METHODS:HIV-1 subtype and drug resistance mutations were assayed among Nigerian patients with treatment failure on first-line therapy (plasma HIV RNA >1000 copies/mL). Sequence analysis of the reverse transcriptase and protease gene revealed drug resistance mutations and HIV-1 viral subtype. Specific patterns of mutations and clinical characteristics are described in patients with the K65R mutation. RESULTS:Since 2005, 338 patients were evaluated. The most prevalent subtypes were CRF02_AG [152 of 338 (44.9%)] and G [128 of 338 (37.9%)]. Three hundred seven of 338 (90.8%) patients had previously received stavudine and/or zidovudine + lamivudine + efavirenz or nevirapine; 41 of 338 (12.1%) had received tenofovir (TDF). The most common nucleoside reverse transcriptase inhibitor mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%). The K65R mutation was present in 37 of 338 patients (10.9%). The Q151M (P < 0.05), K219R, and T69del (P < 0.01) mutations were more common in patients with K65R who had not received TDF. CONCLUSIONS:The K65R mutation is increasingly recognized and is a challenging finding among patients with non-B HIV subtypes, whether or not they have been exposed to TDF.

SUBMITTER: Hawkins CA

PROVIDER: S-EPMC2815152 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.

Hawkins Claudia A CA Chaplin Beth B Idoko John J Ekong Ernest E Adewole Isaac I Gashau Wadzani W Murphy Robert L RL Kanki Phyllis P

Journal of acquired immune deficiency syndromes (1999) 20091001 2

<h4>Introduction</h4>The HIV-1 epidemic in African countries is largely due to non-B HIV-1 subtypes. Patterns and frequency of antiretroviral drug resistance mutations observed in these countries may differ from those in the developed world, where HIV-1 subtype B predominates.<h4>Methods</h4>HIV-1 subtype and drug resistance mutations were assayed among Nigerian patients with treatment failure on first-line therapy (plasma HIV RNA >1000 copies/mL). Sequence analysis of the reverse transcriptase ...[more]

PMID: 19644383

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Project description:WHO recommends starting therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs), i.e. nevirapine or efavirenz, with lamivudine or emtricitabine, plus zidovudine or tenofovir. Few studies have compared resistance patterns induced by efavirenz and nevirapine in patients infected with the CRF01_AE Southeast Asian HIV-subtype. We compared patterns of NNRTI- and NRTI-associated mutations in Thai adults failing first-line nevirapine- and efavirenz-based combinations, using bayesian statistics to optimize use of data.In a treatment cohort of HIV-infected adults on NNRTI-based regimens, 119 experienced virologic failure (>500 copies/mL), with resistance mutations detected by consensus sequencing. Mutations were analyzed in relation to demographic, clinical, and laboratory variables at time of genotyping. The Geno2Pheno system was used to evaluate second-line drug options. Eighty-nine subjects were on nevirapine and 30 on efavirenz. The NRTI backbone consisted of lamivudine or emtricitabine plus either zidovudine (37), stavudine (65), or tenofovir (19). The K103N mutation was detected in 83% of patients on efavirenz vs. 28% on nevirapine, whereas Y181C was detected in 56% on nevirapine vs. 20% efavirenz. M184V was more common with nevirapine (87%) than efavirenz (63%). Nevirapine favored TAM-2 resistance pathways whereas efavirenz selected both TAM-2 and TAM-1 pathways. Emergence of TAM-2 mutations increased with the duration of virologic replication (OR 1.25-1.87 per month increment). In zidovudine-containing regimens, the overall risk of resistance across all drugs was lower with nevirapine than with efavirenz, whereas in tenofovir-containing regimen the opposite was true.TAM-2 was the major NRTI resistance pathway for CRF01_AE, particularly with nevirapine; it appeared late after virological failure. In patients who failed, there appeared to be more second-line drug options when zidovudine was combined with nevirapine or tenofovir with efavirenz than with alternative combinations.

Dataset Information

Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.

Publications

Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.

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