Quantification of HIV-1 proviral DNA in patients with undetectable plasma viremia over long-term highly active antiretroviral therapy

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Forecast model for the evaluation of economic resources employed in the health care of patients with HIV infection

BACKGROUND AND AIMS: The total health care cost for human immunodeficiency virus (HIV) patients has constantly grown in recent years. To date, there is no information about how this trend will behave over the next few years. The aim of the present study is to define a pharmacoeconomic model for the forecast of the costs of a group of chronically treated patients followed over the period 2004-2009.; METHODS: A pharmacoeconomics model was built to describe the probability of transition among different health states and to modify the therapy over time. A Markov model was applied to evaluate the temporal evolution of the average cost. The health care resources exploited during hospitalization were analyzed by using an "activity-based costing" method.; RESULTS: The Markov model showed that the mean total cost, after an initial increase, tended to remain stable. A total of 20 clinical records were examined. The average daily cost for each patient was EUR 484.42, with a cost for admission of EUR 6781.88.; CONCLUSION: The treatment of HIV infection in compliance with the guidelines is also effective from the payer perspective, as it allows a good health condition to be maintained and reduces the need and the costs of hospitalizations

Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitors to regimens containing NRTI plus non-NRTI or only NRTI

BACKGROUND: Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce. METHODS: Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after the switch, and last visit). Finally, we explored whether the CD4+ counts evolved differently in patients who switched to NNRTI or NRTI-only regimens by considering: the overall CD4+ trends, the time to CD4+ 65 500/mm3 after the switch, and the area-under-the-curve (AUC) of the CD4+ after the switch. RESULTS: Eight hundred and ninety-six patients, followed for a median of 2,121 days, were included. At TPLR, hinges occurred in 581/844 (68.9%), but in only 40/581 (6.9%) within a time interval (180 days) compatible with a possible relationship to the switch; furthermore, in 19/40 cases, CD4+ counts appeared to decrease after the hinges. In comparison with the NNRTI group, the NRTI group showed CD4+ count greater at baseline (P = 0.0234) and before the switch (P 64 0.0001), superior CD4+ T-cell increases after HAART was started, lower probability of not achieving CD4+ 65 500/mm3 (P = 0.0024), and, finally, no significant differences in the CD4+ T-cell AUC after the switch after adjusting for possible confounders (propensity score and pre-switch AUC). Persistence at CD4+ < 200/mm3 was observed in 34/435 (7.5%) patients, and a decrease below this level was found in only 10/259 (3.9%) with baseline CD4+ 65 350/mm3. CONCLUSIONS: Switching from first-line PI to NNRTI- or NRTI-based regimens did not seem to impair CD4+ trend over long-term follow-up. Although the greater CD4+ increases in patients who switched to the NRTI-only regimen was due to higher CD4+ counts before the switch, several statistical analyses consistently showed that switching to this regimen did not damage the ongoing immune-reconstitution. Lastly, the observation that CD4+ T-cell counts remained low or decreased in the long term despite virological success merits further investigation

Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: Final results of two randomised, placebo-controlled trials

BACKGROUND: Two randomised, placebo-controlled trials-BENCHMRK-1 and BENCHMRK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end of the study). METHODS: Integrase-inhibitor-naive patients with HIV resistant to three classes of drug and who were failing antiretroviral therapy were enrolled. Patients were randomly assigned (2:1) to raltegravir 400 mg twice daily or placebo, both with optimised background treatment. Patients and investigators were masked to treatment allocation until week 156, after which all patients were offered open-label raltegravir until week 240. The primary endpoint was previously assessed at 16 weeks. We assessed long-term efficacy with endpoints of the proportion of patients with an HIV viral load of less than 50 copies per mL and less than 400 copies per mL, and mean change in CD4 cell count, at weeks 156 and 240. FINDINGS: 1012 patients were screened for inclusion. 462 were treated with raltegravir and 237 with placebo. At week 156, 51% in the raltegravir group versus 22% in the placebo group (non-completer classed as failure) had viral loads of less than 50 copies per mL, and 54% versus 23% had viral loads of less than 400 copies per mL. Mean CD4 cell count increase (analysed by an observed failure approach) was 164 cells per μL versus 63 cells per μL. After week 156, 251 patients (54%) from the raltegravir group and 47 (20%) from the placebo group entered the open-label raltergravir phase; 221 (47%) versus 44 (19%) completed the entire study. At week 240, viral load was less than 50 copies per mL in 193 (42%) of all patients initially assigned to raltegravir and less than 400 copies per mL in 210 (45%); mean CD4 cell count increased by 183 cells per μL. Virological failure occurred in 166 raltegravir recipients (36%) during the double-blind phase and in 17 of all patients (6%) during the open-label phase. The most common drug-related adverse events at 5 years in both groups were nausea, headache, and diarrhoea, and occurred in similar proportions in each group. Laboratory test results were similar in both treatment groups and showed little change after year 2. INTERPRETATION: Raltegravir has a favourable long-term efficacy and safety profile in integrase-inhibitor-naive patients with triple-class resistant HIV in whom antiretroviral therapy is failing. Raltegravir is an alternative for treatment-experienced patients, particularly those with few treatment options

Fast relapse and high drop out rate of 48 weeks daily interferon monotherapy in HIV-infected patients with chronic hepatitis C

BACKGROUND: The standard of care for HCV Hepatitis is the combination of interferon (IFN) plus Ribavirin. In HIV patients the use of this combination therapy may induce drug interactions, and reduces the adherence to HAART. The aim of this study is to evaluate safety and efficacy of a 48 weeks daily dose IFN schedule. METHODS: We evaluated 50 coinfected patients; alpha IFN 2a was administered at a dose of 3 MU daily. The baseline values were the following : CD4+ 515 cells/mmc (mean); HIV-RNA <50 copies/ml in all patients; HCV-RNA 28, 3 × 106 copies/ml. RESULTS: At 48 weeks, 10 patients (20%) achieved a biochemical and virological response according to an intention to treat analysis. Twenty four patients (48%) underwent a drop-out mainly by side effects related to overlapping toxicity of interferon and antiretroviral therapy. All the patients, who responded to the treatment, showed a fast relapse one month after the end of treatment. CONCLUSION: Although our results demonstrated a very poor outcome and a bad tolerance to interferon monotherapy, this approach should not be dropped out, mainly in patients at high risk for side effects and in those with cirrhosis who do not tolerate or are at increased risk for the use of ribavirin