Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial.

BACKGROUND: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. METHODS: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+<200/µL and/or CD4+ recovery ≤ 25% and HIV-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48. RESULTS: By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥ 25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. CONCLUSIONS: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations. TRIAL REGISTRATION: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858.

HAART simplification with lopinavir/ritonavir monotherapy in HIV/HCV co-infected patients starting anti-HCV treatment: a randomised pilot study (KaMon study).

The aim of this randomised, prospective, open-label, multicentre pilot clinical trial was to compare the 48-week toxicity profile of lopinavir/ritonavir (LPV/r) monotherapy with LPV/r-based HAART (KaMon = Kaletra monotherapy) in HIV/HCV patients undergoing HCV treatment. The study involved 30 HIV/HCV co-infected patients naive to anti- HCV therapy. One patient in each arm (6.7%) discontinued anti-HCV therapy because of adverse events. There were no significant between-group differences in terms of the proportion of patients experiencing AEs (p=0.999) or the number of grade 3-4 AEs (p=0.146). No HIV failure was observed. The safety profile of LPV/r monotherapy was similar to that of LPV/r-based HAART, thus encouraging HAART simplification in patients receiving anti-HCV treatment.

Efficacy and safety of a salvage regimen based on tipranavir, enfuvirtide and three nucleoside analogues in HIV1 infected patients with clinical progression: 96-week evaluation.

In recent years, novel antiretroviral drugs have become available for multi-experienced HIV-infected patients with limited options. We enrolled seven advanced HIV-patients, failing multiple previous HAART regimens, in virological failure on their current HAART regimen and showing recent clinical and immunological progression. All patients were prescribed a double-boosted tipranavir plus enfuvirtide based regimen, in addition to zidovudine, tenofovir and lamivudine for salvage therapy. To assess susceptibility to tipranavir, the tipranavir genotypic resistance score was calculated and two years later this was re-evaluated on an updated tipranavir genotypic score algorithm. At baseline, CD4 were 139/mcL (more or less 145), HIV-1 RNA was 822,700 cp/mL. All patients achieved HIV-1 RNA levels less than 400 cp/mL between 12 weeks and 24 weeks of observation; two reached less than 50 cp/mL during this period. At 48 weeks three patients had reached less than 50 cp/mL; three other patients had HIV RNA less than 200 cp/mL. At 72 and 96 weeks HIV viraemia was less than 50 cp/mL in six patients; CD4 T-cell counts 285/mcL (more o less 198). No AIDS-defining events were recorded. Adverse events did not need to stop or change HAART. Strong 3 NRTI backbone could help efficacy and durability, and frequent evaluations in complex patients can help to manage toxicity.