Female genital tract shedding of HIV-1 is rare in women with suppressed HIV-1 in plasma

Objective: Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation.Design:We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS).Methods:HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL; limit of quantitation less than 20-4000copies/ml depending on year of collection) for a median of 7.1 years [interquartile range (IQR) 3.4-9.8, Group 1] or for a median of 1.0 years (IQR=0.5-1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers.Results:HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for 1 year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART.Conclusion:ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation. Copyright © 2019 The Author(s)

Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/μL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates

Types of Stroke among People Living with HIV in the United States

Background: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes.Setting: CNICS, a U.S. multisite clinical cohort of PLWH in care.Methods: We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort.Results: Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes.Conclusion: Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH

Association Between Bilirubin, Atazanavir, and Cardiovascular Disease Events Among People Living With HIV Across the United States

Objective: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH). Methods: Potential myocardial infarctions (MIs) and strokes were centrally adjudicated. We examined MI types: type 1 MI (T1MI) from atherosclerotic plaque instability and type 2 MI (T2MI) in the setting of oxygen demand/supply mismatch such as sepsis. We used multivariable Cox regression analyses to determine associations between total bilirubin levels and outcomes adjusting for traditional and HIV-specific risk factors. To minimize confounding by hepatobiliary disease, we conducted analyses limited to bilirubin values <2.1 mg/dL; among those with fibrosis-4 values <3.25; and among everyone. We repeated analyses stratified by hepatitis C status and time-updated atazanavir use. Results: Among 25,816 PLWH, there were 392 T1MI and 356 T2MI during follow-up. Adjusted hazard ratios for the association of higher bilirubin levels with T1MI were not significant. Higher bilirubin levels were associated with T2MI. By contrast, among PLWH on atazanavir, higher bilirubin levels were associated with fewer T2MI (hazard ratio 0.56:0.33-1.00). Higher bilirubin levels among those on atazanavir were associated with fewer T1MI combined with ischemic stroke. Limitations: Analyses were conducted with total rather than unconjugated bilirubin. Conclusions: Among PLWH, higher bilirubin levels were associated with T2MI among some subgroups. However, among those on atazanavir, there was a protective association between bilirubin and T2MI. These findings demonstrate different associations between outcomes and elevated bilirubin due to diverse causes and the importance of distinguishing MI types

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

CONTEXT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. OBJECTIVE: To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. DATA SYNTHESIS: Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. CONCLUSION: New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis