Antiretroviral drug reduction in highly experienced HIV-infected patients receiving a multidrug regimen: the ECOVIR study.

OBJECTIVES: In a context of life-long therapy, we asked whether it could be possible to reduce the number of antiretroviral drugs without jeopardizing viral suppression. METHODS: ECOVIR was a prospective study aiming to assess whether in patients on combination ART with ≥4 antiretrovirals for ≥24 weeks and virally suppressed for ≥48 weeks, a drug-reduced (DR) regimen could be proposed. The intervention consisted of discontinuing genotypically less susceptible drugs to reach a DR regimen with ≤3 antiretrovirals. The primary endpoint was the proportion of patients maintaining viral suppression at week (W) 24. RESULTS: From 89 eligible individuals for the study, a DR regimen was proposed in 86 (97%) patients, of whom 71 were switched to a DR regimen. Baseline characteristics [median (IQR)] were: age 58 (53-65) years, duration of treatment 24 (21-26) years and viral suppression 8 (6-11) years. The cumulative resistance profile showed full resistance to lamivudine/emtricitabine (91%), abacavir (74%), efavirenz/nevirapine (70%), rilpivirine (56%), darunavir (q24h/q12h) (42%/29%), lopinavir (69%), atazanavir (71%) and raltegravir (24%). The final DR regimen consisted of a two-drug or three-drug regimen in 54 patients (76%) and in 17 patients (24%), respectively. The success rate of a DR regimen at W24 was 93.9% (95% CI 84.4-97.6, Kaplan-Meier estimate). Four patients experienced virological failure (at W4, W8 and W12), all with plasma viral load (pVL) <600 copies/mL and no emergence of resistance mutations. The DR strategy allowed a monthly cost saving of 36%. CONCLUSIONS: In experienced patients with high-level resistance, individualized strategies based on expert advice can offer DR regimen options with fewer drug-drug interactions and a significant economic impact while ensuring virological success.

Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study.

To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile.

Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients.

So far, no study has examined the real impact of tenofovir (TDF)-regimen failure taking into account all patients in a current clinical practice. The aim of this study was to compare the nucleoside reverse transcriptase inhibitors (NRTIs) mutation profiles observed before TDF initiation and after TDF-regimen failure. All patients with genotypic resistance tests performed in this context were selected from the database of the department of virology. The patients were categorized in two groups according to the presence (group I) or absence (group II) of thymidine analogue mutations (TAMs) documented before starting TDF. The proportions of the two groups were compared using Chi-squared tests. Odds-ratios were analyzed with a regression logistic test. Ninety-six patients met the criteria. The median number of TAMs before TDF initiation did not change at failure. The K65R mutation, absent from all baseline genotypes, developed in 19 of the 96 patients, with an incidence significantly higher in group II than in group I. In addition, five genotypes harboring K65R with TAMs or L74V mutation were observed at failure. The changes regarding the other NRTI-associated mutations concern mostly the codons 74, 75, 115, and 118. The selection of K65R was closely linked to the absence of TAMs at baseline and to the regimens sparing both protease inhibitors (PIs) and non-NRTIs. The K65R mutation can emerge even with TAMs or L74V. No obvious impact was shown on the TAMs or other NRTI mutations, although a trend towards emergence of some particular mutations was observed.

Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution.

We analysed the quasispecies at a clonal level in patients whose plasma genotypic test harboured K65R with L74V or thymidine analogue mutations (TAM). We showed that the K65R and TAM such as M41L, D67N, T215Y/D, L210W and K219E can be borne by the same virus. We found no clone bearing both K65R and L74V substitutions. Moreover, the S68G and V75I mutations are not necessarily linked with K65R, and could thus have their own resistance effect.

Long-term virological outcome in patients infected with multi-nucleoside analogue-resistant HIV-1.

The emergence of HIV strains that are resistant to antiretroviral drugs is a major cause of treatment failure. Two sets of mutations: the Q151 M complex and the 69 insert, cause resistance to multiple nucleoside analogues. We report the response to treatment in 12 patients with multiple NRTI-resistant HIV-1 strains. Seven of 12 patients (58%) were able to maintain a viral load below 200 copies/ml at week 48. The patients most likely to obtain therapeutic success were those having no or low-level resistance to non-nucleoside reverse transcriptase inhibitors and/or protease inhibitors. New and more effective drugs are needed for patients with HIV-1 that is resistant to more than one of the current three classes of HIV drugs.