A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression.

BACKGROUND: Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression. METHODS: We randomly assigned 333 HIV-1-infected patients on lamivudine-containing triple regimens with <200 copies per milliliter for at least 6 months to switch their nucleosides to either abacavir/lamivudine (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment failure ["switching = failure" intention to treat (ITT) analysis, noninferiority margin 12.5%]. Secondary outcomes were time to treatment failure, virological failure, adverse events, and changes in CD4 count, fasting plasma lipids, lipodystrophy, body fat, bone mineral density, and renal function. RESULTS: Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22 patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine group versus none in the tenofovir/emtricitabine group developed virological failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty-three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4 counts and plasma lipids showed higher increments in the abacavir/lamivudine group than in the tenofovir/emtricitabine group. CONCLUSIONS: In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.

Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations.

BACKGROUND: The purpose of our study was to assess the presence of nelfinavir (NFV)-associated resistance mutations at the time of early virological failure in subjects receiving NFV as part of a first protease inhibitor (PI)-based triple regimen. MATERIAL/METHODS: Subjects failing their first PI-based NFV-containing triple regimen were identified in six Spanish hospitals. HIV genotyping was carried out in plasma samples collected at the time of the first viral rebound. RESULTS: Upon initiation of NFV-based therapy, 19 of the 30 subjects (63%) were naïve; 11 (37%) had been exposed to nucleoside analogues. Median HIV-RNA at the time of viral rebound was 4, 180 copies/ml. PCR-amplified products were obtained in 22 subjects (73%). These products were sequenced and primary PI resistance mutations were recognized in 6 patients (27%). All six individuals harbored the D30N mutation, and none presented the L90M mutation. Other PI resistance mutations were present in 5 subjects (at codons 36, 63, 71, 77, 82 and/or 88). Secondary PI resistance mutations were present in another 9 subjects. By contrast, mutations conferring resistance to reverse transcriptase inhibitors were present in 50% of the patients, and the M184V substitution was the most frequently seen. CONCLUSIONS: Nearly 75% of patients failing their first PI-based triple regimen containing NFV do not harbor PI resistance mutations. The D30N substitution, rather than L90M, is the most frequently recognized, which does not challenge the efficacy of further rescue interventions with other PIs. This observation supports the use of nelfinavir as first protease inhibitor.

Different degree of immune recovery using antiretroviral regimens with protease inhibitors or non-nucleosides.

BACKGROUND: Protease inhibitors (PI) produce significant immune recovery in most HIV-infected persons, although toxicity and high pill burden often limit this benefit. Combinations including non-nucleoside reverse transcriptase inhibitors (NNRTI) result in similar virological success, but data on immune reconstitution are scarce. METHODS: Baseline plasma viraemia and CD4 cell counts were recorded from 100 patients who began two nucleoside analogue reverse transcriptase inhibitors plus either one PI or one NNRTI in a case-control study [indinavir (82%) and nevirapine (80%), respectively, were most frequently prescribed]. Only patients with baseline CD4 cell counts < 500 x 10(6) cells/l, good treatment adherence and plasma HIV RNA < 50 copies/ml sustained for 1 year were recruited. RESULTS: A rapid CD4 cell gain occurred within 12 weeks on therapy (average 41.8 x 10(6) cells/l per month), irrespective of treatment. In contrast, a trend towards a better CD4 cell gain was noticed between 12 and 48 weeks with a PI (mean CD4 cell increases per month: 15.2 x 10(6) cells/l using PI and 10.4 x 10(6) cells/l using NNRTI). During this period, the difference between therapy with a PI and a NNRTI reached statistical significance for subjects with baseline CD4 counts < 300 x 10(6) cells/l (17.1 x 10(6) and 6.4 x 10(6) cells/l, respectively; P < 0.05). CONCLUSION: A rapid CD4 cell increase occurred shortly after beginning antiretroviral therapy using either PI or NNRTI. Late increases in CD4 cell counts, mostly owing to newly produced cells rather than redistribution, are more pronounced in therapy using a PI, especially in subjects with lower initial CD4 cell counts.