High frequency of genotypic resistance in HIV‐1‐infected patients on highly active antiretroviral therapy with persistent low level viremia

Abstract

Background: Resistance is a major cause of virologic failure in HIV-1-infected patients; genotypic analyses optimize salvage therapy but technical constraints limit testing in plasma viral load (pVL) below 1000 copies/ml. Nevertheless a great amount of patients are failing therapy with a persistent low viral load, it is possible to obtain genotypic information at lower viremias although slight modifications are required during genotype standard procedures. Objective: To assess genotypic resistance in HIV-1-infected patients with persistent low level viremia and virologic response after switching to genotype-guided salvage therapy. To evaluate viral selection of mutation when previous genotypic information were available. Study design: Cohort prospective study in which eligible patients were at least 18 years old, provided informed consent, were on HAART for at least 12 months with two consecutive pVL between 200–999 copies/ml after achieving and maintaining viral suppression (two pVL <50 copies/ml). Modifications in genotype standard procedures included a larger volume of starting plasma, concentrating the sample by centrifugation and higher viral RNA input. Resistance was defined as the detection of any NRTI, NNRTI or PR major resistance mutations. Virologic response was assessed 12 weeks after salvage therapy. Results: Eighteen patients, 50% male, median age 52, median CD4 405 cells/mm3, median pVL 596 copies/ml, median of number of previous regimens 5, 17 (94%) with successful genotype. Resistance mutations were detected in 14 patients (77%). All patients had NRTI mutations, four patients had NNRTI mutations and ten patients had PR mutations, most common mutations were M41L, D67N, M184V, K103N, M46I, I47V, I54V and L90M. Of these fourteen patients, nine started a genotype-guided salvage regimen and presented a pVL < 50 copies/ml after 12 weeks of follow up. For two patients there was previous genotypic information highlighting the selection and accumulation of resistance mutation during persistent low level viremia. Conclusion: In this group of heavily pretreated patients with persistent low viremia, a high frequency of genotypic resistance was observed; obtaining genotypic information may prevent further accumulation of resistance mutation and preserve future therapeutic options

Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

“…In a population with at least three episodes of a pVL of 40 to 500 cpm within 6 months, Delaugerre et al (68) found at least one new DRM during LLV (median pVL, 134 cpm) in 11/37 (30%) patients followed for a median of 11 months. There is a trend toward greater resistance with higher pVL during LLV (36,45,71,76,77). In one study, new DRM were detected in 0 of 10 patients with a maximum pVL of 51 to 100 cpm, compared with 5 (38%) of 13, with a pVL of 101 to 200 cpm and 15 (48%) of 31, with a maximum pVL of 200 to 1,000 cpm (45).…”