1. Home>
2. Specialty Care>
3. HIV/AIDS>
4. Summary and Comment

Detectable Viremia on Treatment: How Fast Does Resistance Accumulate?

In a cohort of patients with extensive treatment experience and stable CD4-cell counts, genotypic resistance emerged slowly over a median follow-up of 9 months.

Many treatment-experienced patients do not achieve virologic suppression on antiretroviral therapy, but they still derive significant benefit from therapy, with viral loads below, and CD4-cell counts above, their pretreatment baseline levels. A potential downside to this effect is the emergence of increased antiviral-drug resistance. This study describes the evolution of such resistance in a clinical cohort.

Investigators at the University of North Carolina recruited study subjects from an ongoing observational cohort study. Of 1605 eligible patients, 98 had had two genotypic resistance tests performed more than 30 days apart with no change in antiretroviral therapy between the two tests or in the 30 days prior to the baseline test. The interval between tests was considered the time at risk for development of resistance.

The study group had substantial treatment experience; the current regimen was the first for 15% of patients, the second for 11%, the third for 18%, and at least the fourth for 55%. Nearly all patients (98%) were receiving an NRTI, with 55% on a PI-based treatment, 14% on an NNRTI-based treatment, and 16% on an NRTI only. Eighty-eight percent of patients had at least one resistance mutation at baseline.

During a median of 9.3 months between the baseline and follow-up resistance tests (interquartile range, 4.2–15.5 months), median CD4-cell count remained stable (from 246 to 242 cells/mm³), and median viral load increased slightly (from 3.9 to 4.3 log copies/mL). Although 59 patients (60%) acquired at least one incident resistance mutation during this period, the median number of new mutations was only one. The overall incidence rate was 1.61 mutations per person-year at risk. In multivariate analysis, not having mutations at baseline, having an increasing viral load, and having an intermediate level of viremia (3–4 log copies/mL vs. <3 or >4) were independent predictors of mutation development. Despite the accumulation of one or more new mutations, susceptibility to most NRTIs and PIs remained stable for the majority of patients; susceptibility to NNRTIs decreased significantly.

Comment: In this patient population, the resistance "cost" of continuing nonsuppressive antiretroviral regimens appeared to be relatively small. Importantly, the authors’ inclusion criteria might have allowed them to select precisely the sort of patients who are least likely to develop clinically significant resistance (those who have received extensive prior antiretroviral therapy but are stable enough not to require a regimen change between two genotype measurements). These results further support delaying a change in antiretroviral therapy for clinically and immunologically stable patients with multiclass drug resistance and low-level viremia, at least until two or more active drugs are available.

— Paul E. Sax, MD

Published in AIDS Clinical Care October 12, 2005

Citation(s):

Napravnik S et al. HIV-1 drug resistance evolution among patients on potent combination antiretroviral therapy with detectable viremia. J Acquir Immune Defic Syndr 2005 Sep 1; 40:34-40.