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Does Viral-Load Testing Reduce Drug Resistance in Resource-Poor Settings?
Despite viral-load testing, high levels of drug resistance at first virologic failure were found in KwaZulu-Natal, South Africa.
High levels of multiclass resistance have been reported at first treatment failure in resource-poor settings that lack viral-load testing, and prolonged viremia before the recognition of treatment failure has been thought to be responsible.
Researchers studied the resistance patterns of HIV in 115 patients in South Africa who experienced virologic failure while receiving their first potent antiretroviral therapy (ART) regimen. Patients were recruited from two regional referral centers that, unlike most resource-poor settings, had viral-load testing available. More than 97% of the patients were infected with clade C virus. At the time of virologic failure, patients had been on ART (91% on NNRTI-based regimens) for a median of 11 months, but the time on treatment while viremic was not reported. Self-reported adherence was high, with 83% of patients reporting >95% adherence.
Approximately 84% of patients had virus with at least one mutation; 64% of patients had dual-class resistance, and 3% had triple-class resistance. The most common mutations were M184V (64%) and K103N (51%). Thymidine analogue mutations were found in viruses from 32% of patients. Although 20% of patients had received suboptimal NRTI therapy prior to potent ART, mutation rates were not different in this group.
Comment: Access to viral-load testing did not prevent high-level multiclass resistance in this cohort. The degree of resistance seen in this study is comparable to what has been found in resource-poor settings that lack viral-load testing.
What might explain these results? In the multivariate analyses, poor adherence, recent opportunistic infection, low CD4-cell count, and prior suboptimal ART did not predict drug resistance. Based on previous comparisons of resistance patterns in clade C and non-C virus, the preponderance of clade C virus in this study did not seem to influence the high frequency of mutations; however, studies in larger cohorts are needed to better define the resistance characteristics of clade C virus.
Physician training and practice were not described and may have played a role. The 2004 South African ART guidelines recommend viral-load testing every 6 months until the viral load exceeds 5000 copies/mL; at that point, testing should be repeated at 3 months, and, if the viral load remains >5000 copies/mL, a regimen switch should be considered. Whether study clinicians followed these guidelines is unclear; if they did, the delay before switching regimens may not have been substantially shorter than delays in cohorts without viral-load testing.
— Renslow Sherer, MD
Dr. Sherer is the Director of the International AIDS Training Center at the University of Chicago.
Published in AIDS Clinical Care May 5, 2008
Citation(s):
Marconi VC et al. Prevalence of HIV-1 drug resistance after failure of a first highly active antiretoviral therapy regimen in KwaZulu Natal, South Africa. Clin Infect Dis 2008 May 15; 46:1589.
- Medline abstract (Free)