HIV Clinical Trials最新文献

Background: Cabotegravir (GSK1265744) is an integrase strand transfer inhibitor in development as a long-acting (LA) intramuscular injectable suspension for HIV-1 pre-exposure prophylaxis (PrEP).

Objective: We report participant outcomes from the phase IIa ECLAIR study related to tolerability, acceptability, and satisfaction of cabotegravir LA.

Methods: The ECLAIR study (ClinicalTrials.gov identifier, NCT02076178) was a randomized, placebo-controlled study in healthy men not at high risk of acquiring HIV-1. Participants were randomized (5:1) to once-daily oral cabotegravir 30 mg or placebo tablets for 4 weeks, followed by gluteal intramuscular injections of cabotegravir LA 800 mg or saline placebo every 12 weeks. The primary objective was to evaluate the safety of cabotegravir LA over three injection cycles (to Week 41). Secondary objectives assessed the tolerability, satisfaction, and acceptability of cabotegravir LA.

Results: Among 115 participants who received injections in the cabotegravir (n = 94) and placebo (n = 21) groups, 93% (n = 87) and 95% (n = 20) completed the injection phase, respectively. Injection intolerability led to withdrawal in 4 participants (4%) receiving cabotegravir LA. The most frequently reported Grade ≥2 adverse event was injection-site pain. Most participants (74% [n = 67]) receiving consecutive injections favored cabotegravir LA vs oral cabotegravir. Most participants were satisfied with cabotegravir LA (75% [n = 64]), were willing to continue (79% [n = 68]), and would recommend (87% [n = 75]) the therapy.

Conclusions: While Grade ≥2 injection-site pain was common, most participants reported overall satisfaction with and preference for cabotegravir LA, with few discontinuations due to injection intolerance. These findings support investigation of cabotegravir LA as an alternative to daily oral PrEP regimens.

Background: Limited studies have compared the impact of different antiretroviral regimens on soluble markers of inflammation with discordant results.

Methods: In this prospective study, treatment naïve HIV-1-infected patients were included if they started their current regimen with atazanavir/ritonavir (ATV/r) (N = 73, Group 1) or darunavir/ritonavir (DRV/r) (N = 85, Group 2) plus tenofovir/emtricitabine. The analysis of IL-6, MCP-1, sCD163, VCAM-1, ox-LDL, and adiponectine was performed on two stored plasma samples, the first prior to antiretroviral therapy initiation and the second one year after initiation.

Results: The results of our analysis show a difference in ox-LDL between the two groups with higher mean (SD) values in ATV/r based group 608.5 ± 137.4 versus 519.1 ± 119.6 in DRV/r group, after controlling for baseline levels of ox-LDL as well as other potential confounding factors controlled by means of matching design or linear regression modelling.

Conclusions: Our analysis provides further data examining the association between the modulation of vascular inflammatory and of activation markers with specific protease inhibitors-based treatments over one year of exposure to these drugs. The data show little evidence for an association, supporting the notion that antiretroviral regimens has generally poor efficiency in downregulating these soluble markers.

The antiretroviral drug efavirenz (EFV) has been linked to disordered sleep and cognitive abnormalities. We examined sleep and cognitive function and subsequent changes following switch to an alternative integrase inhibitor-based regimen. Thirty-two HIV-infected individuals on EFV, emtricitabine, and tenofovir (EFV/FTC/TDF) without traditional risk factors for obstructive sleep apnea (OSA) were randomized 2:1 to switch to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) or to continue EFV/FTC/TDF therapy for 12 weeks. Overnight polysomnography and standardized sleep and neuropsychological assessments were performed at baseline and at 12 weeks. No significant differences in change over 12 weeks were noted between the two arms in any sleep or neuropsychological test parameter. At entry, however, the rate of sleep disordered breathing (SDB) was substantially higher in study subjects compared to published age-matched norms and resulted in a high assessed OSA rate of 59.4%. Respiratory Disturbance Index (RDI), a measure of SDB, correlated with age- and education-adjusted global neuropsychological Z-score (NPZ) (r = -0.35, p = 0.05). Sleep Maintenance Efficiency, Wake after Sleep Onset, REM Sleep and RDI correlated with domain-specific NPZ for learning and memory (all p-values ≤ 0.05). Among HIV-infected individuals on EFV-based therapy and without traditional risk factors for OSA, sleep and neuropsychological abnormalities do not readily reverse after discontinuation of EFV. High baseline rates of SDB and abnormalities in sleep architecture exist in this population correlating with neuropsychological impairment. The role of HIV immuno-virologic or lifestyle factors as contributing etiologies should be explored. OSA may be an under-recognized etiology for cognitive dysfunction during chronic HIV.

The aim of this study was to determine the effect of supervised exercise and folinic acid supplementation on endothelial function in HIV-infected individuals. A randomized clinical trial, double blinded, was conducted with 16 HIV-infected individuals, antiretroviral therapy (at least 6 months) with undetectable viral load (<50 copies/mL), and CD4 count > 200 cells/mm³. The subjects were randomized to aerobic exercise (n = 5) and daily intake for 4 weeks of 5 mg of folinic acid (n = 6) or placebo (n = 5) groups. To assess endothelial function, venous occlusion plethysmography in the brachial artery by the protocol of reactive hyperemia was performed. The aerobic protocol consisted in cycling exercise, 3 times/week at 60-80% VO₂max, for 4 weeks. Exercise group (Δ6.5 mL/min/100 mL) and folinic acid group (Δ7.3 mL/min/100 mL) improved reactive hyperemia, but no difference was found in placebo group (from Δ -0.3 ml/min/100 ml, time p < 0.001, interaction p = 0.02). Results demonstrate that supervised exercise and folinic acid supplementation in very short term improve endothelial function in HIV-infected individuals. As exercise and folate supplementation are safe and relatively inexpensive, this finding deserves more attention in large randomized clinical trials in an attempt to reduce cardiovascular risk in HIV-infected population.

Background: Exercise training has been shown to be an effective strategy to balance oxidative stress status; however, this is underexplored in people living with HIV/AIDS (PLWHA).

Objective: To evaluate the effects of exercise training on oxidative stress in PLWHA receiving antiretroviral therapy.

Methods: Patients performed 24 sessions (3 times per week, 8 weeks) of either aerobic (AT), resistance (RT), or concurrent training (CT). Glutathione disulphide to glutathione ratio (GSSG/GSH) in circulating erythrocytes and thiobarbituric acid-reactive substances (TBARS) in plasma samples were assessed as oxidative stress markers. Eight PLWAH completed the training protocol (AT =3, RT =3, CT =2). The GSSG/GSH and TBARS values were logarithmically transformed to approximate a normal distribution. A paired t-test was used to determine the differences between baseline and post-training values.

Results: Data-pooled analysis showed a decrease in GSSG/GSH and TBARS after the training period: log GSSG/GSH= -1.26 ± 0.57 versus -1.54 ± 0.65, p = .01 and log TBARS =0.73 ± 0.35 versus 0.43 ± 0.21, p = .01. This was paralleled by a rise in peak oxygen uptake (VO_2peak = 29.14 ± 5.34 versus 32.48 ± 5.75 ml kg^-1 min^-1, p = .04). All the subjects who performed resistance exercises showed an average gain of 37 ± 8% in muscle strength with no difference between performing single or multiple sets in terms of muscle strength gain. The results reinforce the clinical importance of exercise as a rehabilitation intervention for PLWHA and emphasizes the safety of exercise at the physiological level with the potential to mediate health outcomes.

Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA <50 copies per mL), in all patients who received at least one dose of study drugs (modified intention-to-treat analysis). Missing information was treated as failure. We assessed safety in all patients. Results We enrolled and randomly assigned treatment to 33 patients (17 in raltegravir group) between June 2015 and June 2017. The study was interrupted by the IRB because a significant difference between arms was detected in an interim analysis. All patients completed follow up at delivery. At delivery, virological suppression was achieved by 13/17 (76.5%) of patients in raltegravir group, versus 4/16 (25.0%) in lopinavir/ritonavir group (RR 3.1, 95% CI: 1.3-7.4). Patients in raltegravir group had significantly higher proportion of virological suppression at 2, 4, and 6 weeks than lopinavir/ritonavir group. Adverse events were most of mild intensity, but patients in lopinavir/ritonavir group had significantly more gastrointestinal adverse events. There was neither discontinuation nor deaths in this trial. Conclusion Raltegravir might be a first-line option for treatment of HIV-infected late-presenting pregnant women.

Background: Although HIV therapy is delivered to millions globally, treatment default (especially soon after entering care) remains a challenge. Community health workers (CHWs) can provide many services for people with HIV, including in rural and resource-limited settings.

Objectives: We designed and implemented a 32 site community randomized trial throughout southern Ethiopia to assess an intervention using CHWs to improve retention in HIV care.

Methods: Sixteen district hospital and 16 local health center HIV clinics were randomized 1:1 to be intervention or control sites. From each site, we enrolled adults newly entering HIV care. Participants at intervention sites were assigned a CHW who provided: HIV and health education; counseling and social support; and facilitated communication with HIV clinics. All participants are followed through three years with annual health surveys, plus HIV clinic record abstraction including clinic visit dates. CHWs record operational data about their client contacts.

Results: 1799 HIV patients meeting inclusion criteria were enrolled and randomized: 59% were female, median age = 32 years, median CD4 + count = 263 cells/mm³, and 41% were WHO Stage III or IV. A major enrollment challenge was fewer new HIV patients initiating care at participating sites due to shortage of HIV test kits. At intervention sites, 71 CHWs were hired, trained and assigned to clients. In meeting with clients, CHWs needed to accommodate to various challenges, including HIV stigma, distance, and clients lacking cell phones.

Conclusions: This randomized community HIV trial using CHWs in a resource-limited setting was successfully launched, but required flexibility to adapt to unforeseen challenges.

Background: Hyperlipidaemia is a risk factor for the progression of chronic kidney disease (CKD), which is a frequent comorbidity in patients with HIV-1 infection, but the renal effects of statins remain unclear.

Methods: We performed an observational, prospective study of HIV-infected patients on suppressive antiretroviral therapy, with CKD and hyperlipidaemia, and starting a lipid-lowering treatment with rosuvastatin, atorvastatin or omega-3 fatty acids. CKD was defined as an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m² for >3 months.

Results: As a whole, 69 patients (53 men, 58 Caucasian, median age 56.2 years) were enrolled. Overall, 25 patients started rosuvastatin (10 mg daily, group A), 23 patients atorvastatin (20 mg daily, group B), and 21 started omega-3 fatty acids (3 g daily, group C). At baseline, median eGFR was 54.4 mL/min/1.73 m², and the eGFR ranged between 50 and 60 mL/min/1.73 m² in 87% of patients. After 12 months, the median eGFR decline was significantly lower in group A (-0.84 mL/min/1.73 m²) and in group B (-0.91 mL/min/1.73 m²) in comparison with the group C (-1.53 mL/min/1.73 m²; p < 0.001 for both comparisons). The median decrease in prevalence of proteinuria and high-sensitivity C-reactive protein was also significantly greater in groups A and B than in group C, while the incidence of treatment discontinuations was comparable across the three groups.

Conclusion: In our study, rosuvastatin and atorvastatin showed a significant protective effect on the renal function compared to omega-3 fatty acids in HIV-1-infected patients with CKD and dyslipidaemia.

Background Russia continues to have an uncontrolled HIV epidemic and its per capita alcohol consumption is among the highest in the world. Alcohol use among HIV-positive individuals is common and is associated with worse clinical outcomes. Alcohol use and HIV each lead to microbial translocation, which in turn results in inflammation. Zinc supplementation holds potential for lowering levels of biomarkers of inflammation, possibly as a consequence of its impact on intestinal permeability. This paper describes the protocol of a double-blinded randomized placebo-controlled trial of zinc supplementation in St. Petersburg, Russia. Methods Participants (n = 254) were recruited between October 2013 and June 2015 from HIV and addiction clinical care sites, and non-clinical sites in St. Petersburg, Russia. Participants were randomly assigned, to receive either zinc (15 mg for men; 12 mg for women) or placebo, daily for 18 months. The following outcomes were assessed at 6, 12, and 18 months: (1) mortality risk (primary outcome at 18 months); (2) HIV disease progression; (3) cardiovascular risk; and (4) microbial translocation and inflammation. Adherence was assessed using direct (riboflavin) and indirect (pill count, self-report) measures. Conclusion Given the limited effectiveness of current interventions to reduce alcohol use, zinc supplementation merits testing as a simple, low-cost intervention to mitigate the consequences of alcohol use in HIV-positive persons despite ongoing drinking.