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.

Long-term adherence to first-line highly active antiretroviral therapy in a hospital-based cohort: predictors and impact on virologic response and relapse.

A high level of adherence to highly active antiretroviral therapy (HAART) is essential to minimize the risk of treatment failure and HIV disease progression. This cohort study evaluated the prevalence and predictors of long-term adherence with first-line HAART in a hospital-based unselected sample of HIV patients from central Italy, and examined the association between adherence and virological response or relapse. Between July 1996 and June 2004, 171 patients (67.3% males; mean age, 41.2 years) were followed for at least 24 weeks and up to 8 years. Adherence was measured by patient self-reports and confirmed using pharmacy records. The prevalence of high-level adherence (>or=90%) at 6 months was 88.3%; slightly less than 80% at 12 months. The incidence of adherence failure in the sample remained fairly stable until 24 months of follow-up, then it declined about 5% every 6 months. Cox analysis showed that compared to single/separated patients, homeless and married persons were, respectively, 1.95 times more likely and two times less likely to experience adherence failure (p < 0.05). The adjusted risk of adherence failure among patients who did not suffer drug-related toxicity was 0.57 (p < 0.05). Medication adherence was significantly associated with shorter time to virological response and longer time to relapse. Adherents were 1.69 times more likely to achieve viral suppression and nine times less likely to experience relapse than nonadherents (p < 0.01). Efforts at improving adherence should be prolonged for at least 24 months. A protective role of marriage for adherence failure is promising but requires confirmation in further research, that should also clarify the exact mechanisms determining the association.

-Dual nucleoside therapy for HIV infection: analysis of results and factors influencing viral response and long term efficacy.

We performed a retrospective analysis of our experience with dual nucleoside regimens to look for predictors of long term benefit. The study evaluated a cohort of 68 HIV-infected patients treated at 3 Italian hospital-based facilities. The results were evaluated using univariate and multivariate statistical analysis. Fourty-three males and 25 females were treated for 22 +/- 14 months. Sixty three patients (92.6%) suffered no or low-grade side-effects. Thirty-four patients (50%) reached a viral load <400 copies/ml (undetectable). Viremia remained persistently undetectable in 9 cases (13.2%). Variable relapses of viremia were seen in 13 patients (19.1%) even though their therapys were not modified. Eight patients (11.8%) showed relapsing viremias persistently around or below 10,000 copies/ml. All patients reaching undetectable viremia but one showed increasing or stable CD4+ cell counts. Factors predicting favourable response were: pre-treatment CD4+ T-cells >150/microl, pre-treatment viremia <50,000 copies/ml, pre-treatment lymphocytes >1,500/microl, and no previous exposure to NRTI. Total lymphocyte counts and CD4+ T-cells showed a significant correlation. Dual NRTI regimens may be still considered for patients unable to tolerate HAART regimens and presenting with favourable predictors of response.