Frequent Virologic Monitoring Limits NRTI and NNRTI Resistance

Summary and Comment |
May 7, 2012

Frequent Virologic Monitoring Limits NRTI and NNRTI Resistance

  1. Salim S. Abdool Karim, MD, PhD

Ongoing virologic monitoring, along with strict application of criteria for regimen switches, was associated with low rates of resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors, which in turn preserved second-line treatment options.

  1. Salim S. Abdool Karim, MD, PhD

The rapid scale-up of antiretroviral therapy (ART) during the past decade has led to dramatic reductions in morbidity and mortality. Efforts are now focused on maintaining virologic control to minimize the development of drug resistance and the need for switches to second-line therapy. Regular viral-load monitoring is recommended for detecting treatment failure but is not always readily available. Two recent reports highlight the benefits of such monitoring.

Barth and colleagues detailed the consequences of drug resistance accumulating during first-line therapy in a cohort of 836 patients in South Africa who were infected with HIV subtype C. All the patients received nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line therapy and underwent viral-load testing two or three times annually. Of the 642 patients who achieved virologic suppression, 145 subsequently experienced viral rebound. Most either switched regimens or were counseled and reestablished suppression; however, 58 continued their first-line treatment despite ongoing viremia. These patients experienced a rapid accumulation of drug-resistance mutations that severely limited their future treatment options: In the 6 to 12 months after first detection of failure, the mean number of mutations per person increased from 2.8 to 4.3, and drug-resistance patterns became increasingly complex, with the total number of thymidine analogue mutations increasing from 4 to 14 and K65R mutations increasing from 3 to 6.

Wallis and colleagues described the resistance profiles of 812 patients in South Africa who were infected with HIV subtype C and underwent viral-load testing every 3 months after initiating ART. After 2 years, 83 patients (10%) experienced virologic failure on first-line therapy: 61 of these patients had evidence of mutations associated with nucleoside or NNRTI resistance (46 had M184V, 28 had K103N, and 13 had Y181C), whereas the remaining 22 patients had no detectable resistance mutations, which could be an indication of suboptimal adherence. Thymidine analogue mutations, associated with cross resistance, were infrequent. Overall, these mutation patterns were less complex than those previously reported in the region for patients who were on similar regimens but were presumably not monitored as frequently.

Comment

Together, these studies show that when patients remain on a given regimen despite ongoing viremia, they risk rapid accumulation of resistance that severely limits their options for future treatment. Frequent viral-load monitoring, along with strict application of criteria for regimen switching, reduces the amount of time that patients spend on failing regimens and thus limits the development of complex resistance patterns. As Barth and colleagues note, wider access to resistance testing at first signs of virologic failure could help differentiate between inadequate adherence and treatment failure.

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