ABSTRACT
BACKGROUND: The widespread use of antiretroviral agents and the growing occurrence of HIV-1 strains resistant to these drugs have given rise to serious concerns regarding the transmission of resistant viruses to newly infected persons, which may reduce the efficacy of a first-line antiretroviral therapy. METHODOLOGY: RNA was extracted from plasma samples of 98 treatment-naïve individuals with a plasma HIV RNA viral load of at least 1,000 copies/ml. Both protease (pr) and reverse transcriptase (rt) were amplified and sequenced using an automated sequencer. National Agency for AIDS Research (ANRS) and Stanford HIV database algorithms were used for interpretation of resistance data. RESULTS: In the protease segment, various minor mutations were present in the majority of the sequenced samples with high frequencies. Only two major mutations, M46L and V82L, were separately found in three individuals of 71 (4.2%) with one carrying both mutations. In the reverse transcriptase gene, no NNRTIs-associated resistance mutations were detected. Only one patient of 70 (1.4%) carried the F77L mutation that is associated with NRTIs resistance. Genetic subtyping revealed that 74.6% of samples were infected with subtype B, 15.5% with CRF02_AG, 4.2% with CRF01_AE, 1.4% with C, 2.8% with G and 1.4% with subtype F2. CONCLUSIONS: The low prevalence of major mutations associated with resistance to antiretroviral drugs (ARVs) among drug-naïve individuals studied suggests that the routine of drug resistance testing may be unnecessary for all Moroccan individuals newly diagnosed or all patients beginning antiretroviral therapy. Nevertheless, continuous surveillance is required since greater access to antiretroviral drugs is expected in Morocco.
Subject(s)
Drug Resistance, Viral , HIV Protease Inhibitors/pharmacology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/genetics , Mutation, Missense , Reverse Transcriptase Inhibitors/pharmacology , Adult , Anti-HIV Agents/pharmacology , Female , HIV Infections/virology , HIV-1/drug effects , HIV-1/isolation & purification , Humans , Male , Middle Aged , Morocco , Plant Extracts , Polymerase Chain Reaction , RNA, Viral/genetics , RNA, Viral/isolation & purification , Sequence Analysis, DNA , Young AdultABSTRACT
Mutations in the Connexin 26 gene (GJB2/Cx26) are responsible for more than half of all cases of prelingual nonsyndromic recessive deafness in Caucasians. The carrier frequency of the 35delG-GJB2 mutation was found to be as high as 2-4% in the Mediterranean populations. Different GJB2 mutations were reported in the Moroccan patients with autosomal recessive nonsyndromic hearing loss; however, rare studies were carried out on the carrier frequencies of these mutations in the healthy populations. The aim of this study was to estimate the carrier frequencies of the GJB2 mutations in the Moroccan population. The molecular analysis of the 35delG mutation and other GJB2 sequence variations was performed in 386 healthy unrelated Moroccan individuals with no known hearing loss. Five GJB2 sequence variations at heterozygous state were found: two mutations, 35delG and 109G > A (V37I), and three polymorphisms, 79G > A (V27I), 341G > A (E114G), and 457G > A (V153I). The carrier frequency of the 35delG mutation was the highest with 2.07% [95% confidence interval (0.90-4.04%)], followed by that of the V37I mutation with 1.43% (0.06-5.39). The carrier frequency of V27I, E114G, and V153I changes was estimated to be 0.71% (0.01-4.34). This finding shows that the 35delG carrier frequency found here is similar to the one observed in Mediterranean populations. It provides new information about GJB2 carrier rates facilitating the diagnosis and the genetic counseling in the Moroccan population.
