HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme.
BACKGROUND
This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa.


METHODS
This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002-2007). Resistance profiles and mutations relative to timing of known virological failure were examined.


RESULTS
In total, 230 patients (120 treatment-naive and 110 with virological failure) were included: 98% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0-5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had therapy-limiting NNRTI mutations, including K103N (55%), V106M (31%) and Y181C (9%). The M184V mutation was the most common mutation, found in 86 (78%) patients. In total, 10 (9%) patients had the K65R mutation. More individuals tended to develop thymidine analogue mutations when sampling occurred after 6 months of detected therapy failure (10/31 [32%] individuals) compared with those who had genotyping before 6 months (15/79 [19%] patients; P=0.246).


CONCLUSIONS
Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected individuals in South Africa was low during the study period. Patients failing first-line ART most often developed resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, the two drug classes used in first-line therapy. Viral load monitoring in this setting is crucial and individual genotypes in those failing first-line therapy should be considered.
Orrell
Catherine
C
Desmond Tutu HIV Foundation, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. catherine.orrell@hiv-research.org.za
Walensky
Rochelle P
RP
Losina
Elena
E
Pitt
Jennifer
J
Freedberg
Kenneth A
KA
Wood
Robin
R
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase