Virological failure at one year in triple-class experienced patients switching to raltegravir-based regimens is not predicted by baseline factors

We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2-34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4 + cell counts below 50/mm 3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation of efficacy also included CD4 + cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4 + cell count was about 20 cells/mm 3 and mean HIV RNA copy number was 4.9 log 10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95 % CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4 + cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log 10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4 + cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4 + cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events)

Abacavir/lamivudine and tenofovir/emtricitabine in pregnant women with HIV: Laboratory and clinical outcomes in an observational national study

Background: Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study. Methods: Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC. Results: The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P &lt; 0.001), and had lower CD4 counts (475/mm3 vs. 533/mm3, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030). Conclusions: In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors