Similar neurocognitive outcomes after 48 weeks in HIV-1-infected participants randomized to continue tenofovir/emtricitabine + atazanavir/ritonavir or simplify to abacavir/lamivudine + atazanavir.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as "impaired" (defined as either a z-score ≤ - 2 or having 2 or more standardized individual test z-scores ≤ - 1); while higher scores (equaling better performance) were classified as "normal". By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p < 0.05) in the baseline-adjusted performance between treatment groups for any individual test or by z-score. Specific demographic and medical risk factors were evaluated by univariate analysis for impact on neurocognitive performance. Factors with p < 0.10 were evaluated by backwards regression analysis to identify neurocognition-correlated factors after accounting for treatment, assessment, and baseline. Four risk factors at baseline for impaired neurocognition were initially identified: lower CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6 levels, and a history of psychiatric disorder not otherwise specified, however none were found to moderate the effect of treatment on neurocognition. In this aviremic, treatment-experienced population, baseline-adjusted neurocognitive function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r-treated and in the ART-simplified ABC/3TC + ATV treatment groups.

Hospitalization Rates and Reasons Among HIV Elite Controllers and Persons With Medically Controlled HIV Infection.

BACKGROUND: Elite controllers spontaneously suppress human immunodeficiency virus (HIV) viremia but also demonstrate chronic inflammation that may increase risk of comorbid conditions. We compared hospitalization rates and causes among elite controllers to those of immunologically intact persons with medically controlled HIV. METHODS: For adults in care at 11 sites from 2005 to 2011, person-years with CD4 T-cell counts ≥350 cells/mm(2) were categorized as medical control, elite control, low viremia, or high viremia. All-cause and diagnostic category-specific hospitalization rates were compared between groups using negative binomial regression. RESULTS: We identified 149 elite controllers (0.4%) among 34 354 persons in care. Unadjusted hospitalization rates among the medical control, elite control, low-viremia, and high-viremia groups were 10.5, 23.3, 12.6, and 16.9 per 100 person-years, respectively. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio, 1.77 [95% confidence interval, 1.21-2.60]), cardiovascular (3.19 [1.50-6.79]) and psychiatric (3.98 [1.54-10.28]) hospitalization than was medical control. Non-AIDS-defining infections were the most common reason for admission overall (24.1% of hospitalizations) but were rare among elite controllers (2.7%), in whom cardiovascular hospitalizations were most common (31.1%). CONCLUSIONS: Elite controllers are hospitalized more frequently than persons with medically controlled HIV and cardiovascular hospitalizations are an important contributor.

Evaluation of cardiovascular biomarkers in a randomized trial of fosamprenavir/ritonavir vs. efavirenz with abacavir/lamivudine in underrepresented, antiretroviral-naïve, HIV-infected patients (SUPPORT): 96-week results.

BACKGROUND: Rates of cardiovascular disease are higher among HIV-infected patients as a result of the complex interplay between traditional risk factors, HIV-related inflammatory and immunologic changes, and effects of antiretroviral therapy (ART). This study prospectively evaluated changes in cardiovascular biomarkers in an underrepresented, racially diverse, HIV-1-infected population receiving abacavir/lamivudine as backbone therapy. METHODS: This 96-week, open-label, randomized, multicenter study compared once-daily fosamprenavir/ritonavir 1400/100 mg and efavirenz 600 mg, both with ABC/3TC 600 mg/300 mg, in antiretroviral-naïve, HLA-B*5701-negative adults without major resistance mutations to study drugs. We evaluated changes from baseline to weeks 4, 12, 24, 48, and 96 in interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), d-dimer, plasminogen, and fibrinogen. Biomarker data were log-transformed before analysis, and changes from baseline were described using geometric mean ratios. RESULTS: This study enrolled 101 patients (51 receiving fosamprenavir/ritonavir; 50 receiving efavirenz): 32% female, 60% African American, and 38% Hispanic/Latino; 66% (67/101) completed 96 weeks on study. At week 96, levels of IL-6, sVCAM-1, d-dimer, fibrinogen, and plasminogen were lower than baseline in both treatment groups, and the decrease was statistically significant for sVCAM-1 (fosamprenavir/ritonavir and efavirenz), d-dimer (fosamprenavir/ritonavir and efavirenz), fibrinogen (efavirenz), and plasminogen (efavirenz). Values of hs-CRP varied over time in both groups, with a significant increase over baseline at Weeks 4 and 24 in the efavirenz group. At week 96, there was no difference between the groups in the percentage of patients with HIV-1 RNA <50 copies/mL (fosamprenavir/ritonavir 63%; efavirenz 66%) by ITT missing-equals-failure analysis. Treatment-related grade 2-4 adverse events were more common with efavirenz (32%) compared with fosamprenavir/ritonavir (20%), and median lipid concentrations increased in both groups over 96 weeks of treatment. CONCLUSIONS: In this study of underrepresented patients, treatment with abacavir/lamivudine combined with either fosamprenavir/ritonavir or efavirenz over 96 weeks, produced stable or declining biomarker levels except for hs-CRP, including significant and favorable decreases in thrombotic activity (reflected by d-dimer) and endothelial activation (reflected by sVCAM-1). Our study adds to the emerging data that some cardiovascular biomarkers are decreased with initiation of ART and control of HIV viremia. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00727597.

Treatment of HIV in outpatients with schizophrenia, schizoaffective disorder and bipolar disease at two county clinics.

Despite a high prevalence of HIV in patients with serious mental health disorders, there is little information in the literature regarding details of their HIV treatment. The objective of this paper is to assess factors associated with the success of HIV therapy in people with schizophrenia, schizoaffective, and bipolar disease. The methods used are retrospective, post-study chart review, and clinician questionnaire at two HIV county clinics. Forty-nine (4.8%) study patients were identified, 51% of whom achieved an undetectable HIV viral load. These patients tended to have less drug use (42% vs. 68%), more ongoing psychiatric visits (70% vs. 58%) and were more apt to take psychiatric medicines (70% vs. 40%) than patients with detectable HIV viral loads. Both groups had many missed appointments. We were surprised to find that many patients were successful with HIV treatment despite substance abuse, uncontrolled psychiatric symptoms, and lack of psychiatric care. Missing clinic appointments had little influence on treatment outcome.

Primary nasal Kaposi Sarcoma in well-controlled HIV-positive patient with normal CD4 count associated with long-term nasal steroid use.

Kaposi sarcoma (KS) is an angioproliferative disease that is caused by human herpesvirus 8. The epidemic form of KS is associated with acquired immunodeficiency syndrome (AIDS) and is common in HIV-positive patients with CD4 counts less than 200 cells/mm. We present the case of a 63-year-old man with well-controlled HIV and normal CD4 count developing atypical nasal KS associated with intranasal steroid use.

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in Asian Subjects with Human Immunodeficiency Virus 1 Infection: A Sub-Analysis of Phase 3 Clinical Trials.

The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.

Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial.

OBJECTIVE: Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV) was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r) over 24 weeks in a population of virologically suppressed, HIV-1 infected patients. DESIGN: This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥ 6 months with no history of virologic failure and whose HIV-1 RNA had been ≤ 75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1 ∶ 2 to continue current treatment or simplify to ABC/3TC+ATV. METHODS: The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR) algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs), and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers. RESULTS: After 24 weeks, ABC/3TC+ATV (n = 199) was non-inferior to TDF/FTC+ATV/r (n = 97) by both the primary analysis (87% in both groups) and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively), but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30%) compared with the ABC/3TC+ATV group (13%). Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups. CONCLUSIONS: After 24 weeks, simplification to ABC/3TC+ATV from TDF/FTC+ATV/r maintained viral suppression was well-tolerated, and led to improvements in bone and renal biomarkers and HDL cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov NCT01102972 GlaxoSmithKline Clinical Study Register #113734.