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Data on antiretroviral drug resistance among drug-naïve persons are important in developing sentinel surveillance policies. This study was conducted to determine the prevalence of antiretroviral drug resistance mutations among drug-naïve HIV-infected individuals attending a voluntary testing and counselling centre at the Mankweng Hospital in northeastern South Africa. In total, 79 drug-naïve HIV-positive individuals were sequentially recruited during February 2008–December 2008. Drug resistance mutations were determined using the calibrated population resistance tool available on the Stanford HIV drug resistance database. Viral DNA was obtained from 57 (72%) of the 79 individuals. Reliable nucleotide sequences were obtained for 54 reverse transcriptase (RT) and 54 protease (PR) gene regions from 54 individuals. Overall, five sequences (9.3%) harboured drug resistance mutations (95% confidence interval −1.53 to 16.99). Four (7.4%) of these were nucleoside RT inhibitor mutations (D67G, D67E, T69D, and T215Y), and one (1.9%) was a PR inhibitor mutation (M46I). No major non-nucleoside RT resistance mutation was detected. Several minor resistance mutations and polymorphisms common in subtype C viruses were observed in the PR and RT genes. Phylogenetic analysis of the partial pol sequences showed that 52 (96%) of the 54 isolates were HIV-1 subtype C. One isolate (08MB08ZA) was HIV-1 subtype B while another (08MB26ZA) was related to HIV-1 subtype J. HIV-1 subtype recombination analysis with REGA assigned the pol sequence to HIV subtype J (11_cpx) with a bootstrap value of 75%. The prevalence of drug resistance mutations observed in the population studied was relatively higher than previously reported from other parts of South Africa. In addition, this is apparently the first report of an HIV-1 subtype J-like virus from northeastern South Africa.

Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of −482 (p = 1; χ2 = 0.00001) or −455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the −455C genotype, but not in males for the −455T genotype. Viral load decreases were significant with the −455C and −482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders.

Data on genetic polymorphisms associated with response to anti-HIV drugs has accumulated over the years. Information on how polymorphisms influence drug metabolism and transport to target sites is important in guiding dosage or selection of appropriate alternative therapies. This study determined the frequency of MDR1 C3435T and CYP2B6 G516T polymorphisms associated with the transport and metabolism of efavirenz and nevirapine, in a population of South African HIV infected patients. In addition, association of polymorphisms with immunologic and virologic factors was investigated. A 207bp of MDR1 exon 26 and a 161bp of CYP2B6 exon 4 were obtained from patients by polymerase chain reaction. Analysis of population-based sequences of MDR1 revealed a frequency of 89% and 11% of C and T alleles respectively (n=197; X2 = 0.974; p=0.324). Restriction fragment length polymorphism (RFLP) analysis of the CYP2B6 gene revealed a prevalence of 9.5% of GG, 78.4% of GT and 12.1% of TT genotype (n= 199; X2 = 65.204; p=0.00). There was no significant difference between immune recovery and decline in viral load (n=53), with genotype after repeated calculations of analysis of variance (ANOVA).

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