Anna Danise

Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study).

Objective:We compared the immunological and clinical outcomes of lamivudine monotherapy and complete therapy interruption in the treatment of HIV-1-infected patients harbouring lamivudine-resistant virus. Methods:This 48-week, open-label pilot study randomly assigned HIV-infected patients receiving lamivudine-containing HAART and harbouring the M184V mutation to monotherapy with lamivudine 300 mg once daily (lamivudine group) or the discontinuation of all antiretroviral drugs (TI group). The primary endpoint was the occurrence of immunological or clinical failure; immunological failure was defined as the first report of a CD4 T-cell count less than 350 cells/μl, and clinical failure as the occurrence of a Centers for Disease Control and Prevention grade B or C event. The data were analysed on the basis of the intention-to-treat principle. Results:By week 48, 20 of 29 patients in the TI group (69%; 95% CI 51–83%) and 12 of 29 in the lamivudine group (41%; 95% CI 26–59%) had discontinued the study because of immunological or clinical failure, which was significantly delayed in the lamivudine group (P = 0.018). Only patients in the TI group (6/29, 20.7%) experienced grade 3–4 clinical adverse events at least possibly related to HIV-1 (P = 0.02). The mean decline in CD4 cell percentage, viral rebound and recovery of HIV-1 replication capacity were significantly lower in the lamivudine group. The 24-week virological and immunological response after therapy resumption in patients who prematurely discontinued the study was similar in the two groups. Conclusion:In HIV-1-infected patients harbouring a lamivudine-resistant virus, lamivudine monotherapy may lead to a better immunological and clinical outcome than complete therapy interruption.

Switching to unboosted atazanavir improves glucose tolerance in highly pretreated HIV-1 infected subjects

OBJECTIVE To evaluate the 24-week effects on glucose tolerance of switching from a protease inhibitor (PI)-based to an unboosted atazanavir-including regimen in highly pretreated HIV-1 infected subjects with metabolic alterations. DESIGN Prospective, open-label, single-center, 24-week pilot study. METHODS Twenty-one subjects underwent an oral glucose tolerance test (OGTT) at baseline (BL) and after 24 weeks of unboosted atazanavir. Insulin sensitivity and beta-cell responsiveness were evaluated on the basis of static and dynamic data; fasting glucose, insulin, C-peptide, triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), TC/HDL-c ratio, CD4+ cell count and HIV-1 RNA were measured. RESULTS After 24 weeks of unboosted atazanavir, the 120-min glucose level was significantly lower than the one measured at BL (P=0.021); there were no statistically significant differences in the insulin concentration profile. The SI(oral), an OGTT-based index of insulin sensitivity, was significantly higher at week 24 (P=0.017); the indices of first- and second-phase beta-cell responsiveness did not significantly change. There was no significant difference between BL and 24-week fasting glucose, insulin or C-peptide levels, and consequently no change in fasting homeostasis model assessment indices of insulin sensitivity and beta-cell function. There were significant improvements in TG (P=0.009), TC (P=0.0001), LDL-c (P=0.019) and TC/HDL-c ratio (P=0.001), and a similar trend in HDL-c levels (P=0.069). No significant changes in the immunological and virological parameters were detected. CONCLUSIONS Our results show that switching from a PI-based to an unboosted atazanavir-including regimen leads to a significant improvement in glucose tolerance in highly pretreated HIV-1 infected subjects with metabolic alterations.

Resistance to amprenavir before and after treatment with lopinavir/ritonavir in highly protease inhibitor-experienced HIV patients

Anti-hepatitis C virus (HCV) treatment combining IFN-alpha and ribavirin (IFN+R) has still poorly defined effects on immune responses. Frequencies of T helper (Th) type 1 cells specific for HCV, cytomegalovirus (CMV) and HIV were measured in chronically HCV-infected patients with or without HIV co-infection during IFN+R treatment. Although scarce, peripheral blood HCV-specific Th1 cells did not change significantly, while frequencies of HIV and CMV-specific Th1 cells decreased in co-infected patients independently of CD4 cell count changes. This suggests that IFN+R therapy might compromise virus-specific immune defenses in immunosuppressed patients.

The 118i Reverse Transcriptase Mutation Is the Only Independent Genotypic Predictor of Virologic Failure to a Stavudine-containing Salvage Therapy in Hiv-1-infected Patients

Summary: Patients infected with HIV-1 with more than 1000 HIV-1 RNA copies/mL, who were genotyped within 3 months before starting stavudine and treated for at least 3 months with a stable stavudine-containing highly active antiretroviral therapy, were selected from our database to identify the determinants of response to stavudine. Nonresponse was defined as a failure to achieve HIV-1 RNA level of less than 400 copies/mL or a reduction of more than 2 log10 by week 12. Univariate logistic analysis was used to elicit the failure-associated reverse transcriptase mutations (scored 1 to develop a genotype score). Eighty-one patients were eligible for the analysis, including 75 (93%) who previously received zidovudine. Thirty-five (43%) were nonresponders. Univariate logistic analysis revealed the following failure-associated mutations: 41L (P = 0.0001), 44D (P = 0.02), 118I (P = 0.0006), 184V (P = 0.04), 210W (P = 0.0004), and 215Y (P = 0.002) for a median stavudine score of 2. Failure was observed in 7 (18.9%) of 37 patients with a score less than 2, compared with 28 (63.6%) of 44 patients with a score of 2 or greater (P < 0.0001). The multivariable analysis showed that the 118I mutation (P = 0.04) was the only independent genotypic predictor of failing on a stavudine- containing highly active antiretroviral therapy.

Long-Term Response in Patients Receiving HAART Including Nelfinavir: Experience from Two Italian Centers

Abstract Many studies have demonstrated that the long-term, virological, immunolog-ical and clinical effectiveness of highly active antiretroviral therapy (HAART) is mainly related to durable suppression of viral replication. Among the specific antiretroviral agents available today, nelfinavir has been widely used in the last 3 years. This open label, non comparative, retrospective study on 307 patients living with HIV aimed to evaluate the effectiveness of an antiretroviral (ART) regimen including nelfinavir as first-line HAART in terms of rate and durability of viro-immunological response. Most patients, 258/307 (84%), were pre-treated whereas only 49/307 (16%) were treatment naive. The median baseline CD4 cell count was 223 cells/mm3 for naïve patients and 317 cells/mm3 for experienced patients whereas median HIV RNA values were 2,500 and 82,000 copies/ml for experienced and naïve patients respectively. Median times spent on nelfinavir were 839 and 897 days for experienced and naïve patients respectively, with 171/258 pre-treated patients (66%) remaining on nelfinavir-based therapy up to 24 months. Overall, the mean CD4 increase was 196 cells/mm3 with a relevant increment of 165 in experienced patients and 367 cells/mm3 in naïve patients (p<0.01). The mean viral load variation in naïve patients was −2.22 log10 and in experienced patients −0.53 log10 (p<0.01). In conclusion, nelfinavir, as part of HAART, demonstrated long-term benefit (almost two-thirds of patients stayed on nelfinavir up to 24 months). The response rate in patients naïve to antiretroviral therapy was better than for experienced patients. Although there were some differences related to the baseline CD4 level, the overall response rate was good, supporting the role of nelfinavir in HAART.