HIV-1-Resistant Strains during 8-Week on 8-Week off Intermittent Therapy and their Effect on CD4 + T-cell Counts and Antiviral Response

Abstract

Background

We aimed here to study drug-associated HIV resistance mutations in peripheral blood mononuclear cells (PBMC) and plasma during intermittent therapy.

Methods

A substudy of 86 patients randomized to the intermittent treatment arm (8-week on/8-week off) of the ANRS 106 Window trial. HIV reverse transcriptase and protease genes were sequenced and resistance mutations identified according to the International AIDS Society list.

Results

Resistance mutations were detected in PBMC of 27/86 (31%) patients at baseline and 25/72 (35%) patients at week 96. Resistance mutations were detected in plasma of 28/86 (33%), 24/83 (29%) and 33/80 (41%) patients at weeks 8, 40 and 88, respectively. The detection of nucleoside reverse transcriptase inhibitor and protease inhibitor associated resistance mutations in plasma remained stable over time, but there was an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations in patients on an NNRTI-based regimen: 1/33 (3%) versus 7/26 patients (27%) at weeks 8 and 88, respectively (P=0.02). The proportions of patients with plasma HIV RNA levels ≤400 copies/ml after 8 weeks of treatment at weeks 16, 48 and 96 in patients with drug-resistant and wild-type viruses were 93% versus 74% (P=0.04), 96% versus 88% (P=0.43) and 70% versus 84% (P=0.13), respectively. Patients with drug-resistant virus had a lower CD4⁺ T-cell decrease from baseline at weeks 40 and 88 as compared to patients with wild-type virus (P=0.05 and 0.002, respectively).

Conclusions

NNRTI-associated resistance mutations increased over time in plasma of patients who were given NNRTIs. Drug-associated HIV resistance mutations did not seem to impair short-term antiviral response and might be associated with reduced CD4⁺ T-cell loss during interruptions.