Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa : implications for future treatment options.
Green, Taryn N.
Anton, Elizabeth D.
Reeves, Jacqueline D.
Kuritzkes, Daniel R.
Ndung'u, Peter Thumbi.
MetadataShow full item record
Background: Drug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy. Methods: We sequenced the pol gene of viruses from 45 individuals failing at least 6 months of HAART in Durban, South Africa, to determine the prevalence and patterns of drug-resistance mutations. Coreceptor use profiles of these viruses and those from 45 HAART-naive individuals were analyzed using phenotypic and genotypic approaches. Results: Ninety-five percent of HAART-failing patients had at least one drug-resistant mutation. Thymidine analog mutations (TAMs) were present in 55% of patients with 9% of individuals possessing mutations indicative of the TAM1 pathway, 44% had TAM2, whereas 7% had mutations common to both pathways. Sixty percent of HAART-failing subjects had X4/dual//mixed-tropic viruses compared with 30% of HAART-naïve subjects (P < 0.02). Genetic coreceptor use prediction algorithms correlated with phenotypic results with 60% of samples from HAART-failing subjects predicted to possess CXCR4-using (X4/dual/mixed viruses) versus 15% of HAART-naïve patients. Conclusions: The high proportion of TAMs and X4/dual/mixed HIV-1 viruses among patients failing therapy highlight the need for intensified monitoring of patients taking HAART and the problem of diminished drug options (including CCR5 antagonists) for patients failing therapy in resource-poor settings.
Showing items related by title, author, creator and subject.
Can small-scale poultry production contribute to household food security in the Maphephetheni lowlands, KwaZulu-Natal? Mosisi, Moleka Pange. (2009)This study investigated the feasibility of small-scale poultry production to contribute to household food security in the Maphephetheni lowlands in KwaZulu-Natal. Forty households, selected by stratified random sampling ...
Grey, Rebecca Victoria. (2006)The oribi Ourebia ourebi is probably South Africa's most endangered antelope. As a specialist grazer, it is extremely susceptible to habitat loss and the transformation of habitat by development. Another major threat to ...
Ngobese, Nokulunga. (2014)The concept of community garden has been studied in many parts of the world to understand its role in sustainable land use, food security and cultural cohesiveness. In South Africa, the government is exploring the upliftment ...