Study of the Genotypic Resistant Pattern in HIV-Infected Women and Children from Rural West Cameroon

Abstract

The distribution of antiretroviral (ARV) therapy resistance mutations among HIV-1 strains was evaluated in 39 postpartum women, one pregnant woman, and 12 HIV-positive babies (seven newborns and five children) living in rural west Cameroon. Thirty-five women and all newborns received a single dose of nevirapine (NVP) to prevent mother-to-child transmission of HIV-1; two women were ARV treated and three were ARV naive. Of the 52 viral strains examined, three were subtype B, 45 were classified into eight HIV-1 non-B subtypes, and four remained unclassifiable. Sequence analysis for genotypic drug resistance in the reverse transcriptase (RT) gene showed the presence of mutations associated with nonnucleoside RT inhibitor resistance in 20% of the samples from NVP-treated women and in 57% of those from treated newborns. Mutations associated with nucleoside RT inhibitors (M184V in one case and V118I in four cases) were found in five samples, despite being derived from ARV-naive patients. As expected, a greater frequency of mutations was found in the protease gene region. Of the sequences analyzed, 79% harbored five to seven specific mutations. The secondary mutations showed the typical protease inhibitor resistance-associated pattern for non-subtype B viruses, M36I being the predominant mutation (92.5% in women, 100% in babies). Other mutations frequently detected were K20I, L63P, H69K, and I13V. These findings confirm that resistance mutations can be detected in ARV-naive patients infected with non-B subtypes and emphasize an urgent need for studies assessing the impact of these mutations on the efficacy of subsequent ARV therapy and on the appearance of drug-resistant strains.

Response to Nonnucleoside Reverse Transcriptase Inhibitor-Based Therapy in HIV-Infected Children with Perinatal Exposure to Single-Dose Nevirapine

“…9 Our findings suggest that the exposed children had developed resistance mutations to nevirapine, mainly K103N, Y181C, and G190A, as has been demonstrated in studies on resistance in infants following single-dose nevirapine exposure. [2][3][4][5][12][13][14][15][16][17][18] We did not find a difference between the rates of virologic suppression in the exposed children who started an NNRTIcontaining regimen within 6 months of exposure to perinatal single-dose nevirapine and the exposed children who started the NNRTI-containing regimen after 6 months of exposure to single-dose nevirapine, as in previous reports. 9,19 Our results may be explained by the small numbers in our subanalysis, which may not have given us the required power to detect the differences.…”

Trends in Prevalence of HIV‐1 Drug Resistance in Thailand 2009–2010

“…Furthermore, incomplete suppression of viral replication promotes the development of broader drug resistance, compromising subsequent treatment regimens. A number of studies have evaluated rates of resistance mutations in recently transmitted virus by looking at subjects with primary infection (28,29,32,33). Reported rates of drug resistance in these studies vary from 1.4 to 37.0% with most of the resistance mutations seen in the RT gene (23,27,31,(34)(35)(36)(37)(38)(39)(40).…”

Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon

“…In a study from Yaounde, Cameroon it was reported that 2.6% protease drug resistance and 9.3% major reverse transcriptase drug resistance were detected among patients who never received therapy, a finding that has implications for the efficacy of first line therapies [5]. Further in a study conducted at Doula, Cameroon [6] out of 819 patients who received first line ART, 36% had virological failure after 6 months or more. About 80% of drug resistance was detected for Nucleoside Reverse Transcriptase Inhibitors (NRTI) class, followed by the non-nucleoside reverse transcriptase Inhibitors (NNRTI) (76%) and Protease Inhibitor (PI) class (19%) drugs.…”