Background. It is unknown if tenofovir disoproxil fumarate (TDF), which is often coformulated with the lipid-neutral emtricitabine (FTC), has a lipid-lowering effect. Methods. We performed a randomized, crossover, double-blind, placebo-controlled clinical trial on human immunodeficiency virus type 1 (HIV-1)–infected subjects with HIV-1 RNA < 50 copies/mL during ≥6 months on stable darunavir/ritonavir (800/100 mg once daily) or lopinavir/ritonavir (400/100 mg twice daily) monotherapy, fasting total cholesterol (TC) ≥200 mg/dL or low-density lipoprotein cholesterol (LDL-c) ≥130 mg/dL, and no lipid-lowering drugs. In arm 1, TDF/FTC was added for 12 weeks, followed by 12 weeks of placebo (washout) and 12 additional weeks of placebo (placebo period). Subjects in arm 2 added placebo for 12 weeks (placebo period) followed by TDF/FTC for 12 weeks and placebo for 12 additional weeks (washout). The primary endpoint was change in median fasting TC levels. Results. Of 46 subjects enrolled, 56% received darunavir/ritonavir and 44% lopinavir/ritonavir. Exposure to TDF/FTC reduced TC from 234 to 205 mg/dL (P < .001), LDL-c from 155 to 128 mg/dL (P < .001), and high-density lipoprotein cholesterol (HDL-c) from 50.3 to 44.5 mg/dL (P < .001). It also decreased the proportion of subjects with fasting TC ≥200 mg/dL from 86.7% to 56.8% (P = .001), and LDL-c ≥130 mg/dL from 87.8% to 43.9% (P < .001). After 12 weeks, TDF/FTC exposure was associated with lower TC and LDL-c levels than placebo (P = .001 and P = .002, respectively). The TC/HDL-c ratio and triglyceride levels did not change with TDF/FTC exposure. Conclusions. Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF. Clinical Trials Registration. NCT01458977.

Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression. We randomly assigned 333 HIV-1-infected patients on lamivudine-containing triple regimens with <200 copies per milliliter for at least 6 months to switch their nucleosides to either abacavir/lamivudine (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment failure ["switching = failure" intention to treat (ITT) analysis, noninferiority margin 12.5%]. Secondary outcomes were time to treatment failure, virological failure, adverse events, and changes in CD4 count, fasting plasma lipids, lipodystrophy, body fat, bone mineral density, and renal function. Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22 patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine group versus none in the tenofovir/emtricitabine group developed virological failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty-three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4 counts and plasma lipids showed higher increments in the abacavir/lamivudine group than in the tenofovir/emtricitabine group. In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.

To compare 48-week changes in body fat distribution and bone mineral density (BMD) between patients switching from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL) and patients continuing with PI/r. Substudy of the prospective, randomized, open-label, multicenter SPIRAL study. Patients were randomized (1 : 1) to continue with the PI/r-based regimen or switch to RAL, maintaining the rest of the treatment unchanged. Dual-energy X-ray absorptiometry and computed tomography scans were performed at baseline and after 48 weeks to measure body fat and bone composition, analyzing intragroup and intergroup differences. Eighty-six patients were included and 74 patients (39 RAL, 35 PI/r) completed the substudy. Significant increases in median [interquartile range (IQR)] visceral adipose tissue (VAT) [20.7 (-2.4 to 45.6) cm(2), P = 0.002] and total adipose tissue (TAT) [21.4 (-1.3 to 55.4) cm(2), P = 0.013] were seen within the PI/r group. No significant changes in body fat were seen with RAL or between treatment groups. Regarding bone composition, total BMD [0.01 (0 to 0.02) g/cm(2), P = 0.002], total hip BMD [0.01 (0 to 0.03) g/cm(2), P = 0.015] and total hip T score [0.12 (-0.05 to 0.21) SD, P = 0.004] significantly increased with RAL, with no significant changes within the PI/r group. Differences between treatment groups were significant in femoral neck BMD [0.01 (-0.02 to 0.02) g/cm(2), P = 0.032] and T score [0.01 (-0.18 to 0.18) SD, P = 0.016]. Although there were no significant changes in body fat between groups, maintaining a PI/r-based regimen was associated with a significant increase in VAT and TAT. Switching to RAL led to a significant increase in femoral neck BMD when comparing between groups.

Visceral leishmaniasis (VL) is characterized by frequent relapses in HIV-infected patients, even in those who receive secondary prophylaxis. The aim of our study was to evaluate the efficacy of liposomal amphotericin B (L-AMB) for secondary prophylaxis of VL in HIV-infected patients. From January 2001 to December 2005, 17 HIV patients, with at least one previous episode of VL who received L-AMB as secondary prophylaxis for VL, were included in the study. Efficacy was measured as the proportion of patients remaining free (non-relapse) of VL at different time points. Relapses were analysed as time-to-relapse distribution and were evaluated by survival analysis using the Kaplan–Meier method. Twenty-one episodes of VL were diagnosed and nine relapsed. The median follow-up time was 14 (5–44) months. The probability of remaining free of relapse at 6 months was 89.7% (95% CI, 76.2–100); at 12 months, the probability was 79.1% (95% CI, 61–97.2) and at 24 and 36 months, the probability was 55.9% (95% CI, 30.5–81.3). In the non-relapsing group, patients had a significant increase in CD4 cell levels of 102 (10–174) and 126 (4–159) cells/mm³ at 12 and 24 months, respectively (P = 0.037), whereas in the relapsing group, no significant increase was observed. Prophylaxis with L-AMB was well tolerated and only three patients had a mild impairment of renal function without requiring any change in treatment. L-AMB is well tolerated and useful for secondary prophylaxis of VL.

Background: Lipoatrophy is the most stigmatizing side effect of stavudine therapy. We assessed the long-term effects of replacing stavudine with tenofovir in HIV-infected patients with lipoatrophy. Method: Prospective switch study. Sixty-two clinically stable patients with antiretroviral therapy (ART) containing stavudine, HIV-1 RNA <50 copies/mL, and lipoatrophy at least in the face on physical examination were included. All patients switched from stavudine to tenofovir without changing any other drug. Objective (malar ultasonography, bioelectrical impedance analysis) and subjective measures of lipoatrophy were assessed. Results: Median age at baseline was 40 years, 44 patients (71%) were male, and median time on stavudine was 4.8 years. Median malar fat thickness increased 0.8 mm (25%) 24 months after switching. Total fat mass increased 3.9 kg (21%). Plasma lactate levels decreased significantly, mainly in patients with baseline hyperlactatemia (from 3.05 to 1.19 mmol/L). Significant improvement in total cholesterol (−12%), triglycerides (−31%), and total cholesterol/HDL cholesterol ratio (−11%) was observed at Month 24. Conclusions: In this study, switching from stavudine to tenofovir maintained durable virologic suppression when the HAART regimen included a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, led to a slow improvement of lipoatrophy, and improved the lipid profile and lactate levels with excellent tolerability. These results support the proactive change of stavudine to tenofovir.

Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)–infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010–May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV.