Long-Term Kidney Function, Proteinuria, and Associated Risks among HIV-Infected and Uninfected Men in the MACS

Background: Factors affecting kidney function and proteinuria among HIV-positive (HIV+) and HIV-negative (HIV–) persons need better characterization. Methods: We evaluated estimated glomerular filtration rate (eGFR, ml/min per 1.73 m2) changes, proteinuria prevalence (a urine protein-to-creatinine ratio of ≥0.2 at two consecutive visits) and associated factors among HIV+ and HIV− men. Results: There were 917 HIV+ men receiving HAART, 159 HIV+ men not receiving HAART, and 1305 HIV− men seen from October 2003 to September 2014. Median annual eGFR change was −0.5, −0.8% for HIV+ and −0.3% for HIV− men (P < 0.001). Factors significantly (P < 0.05) associated with more than 3% annual eGFR decline were HAART receipt (but no specific antiretroviral drug), age more than 50, hypertension, diabetes, current smoking. Proteinuria existed in 14.9% of visit-pairs among HAART recipients, 5.8% among non-HAART recipients, and 1.9% among HIV− men, and was associated with subsequent annual more than 3% eGFR decline (odds ratio 1.80, P < 0.001). Proteinuria-associated factors also included HAART use (vs. HIV−), age at least 50 (vs. <40), diabetes, hypertension, current smoking, hepatitis C virus-infection (all P < 0.05) and, among HIV+ men, lower CD4+ cell count, didanosine, saquinavir, or nelfinavir use (all P < 0.05). After adjusting for proteinuria, among HAART users, having a detectable HIV RNA, cumulative use of tenofovir disoproxil fumarate, emtricitabine, ritonavir, atazanavir, any protease inhibitor, or fluconazole were associated with more than 3% annual eGFR decline. Conclusion: Longitudinal kidney function decline was associated with HAART use but no individual antiretroviral drug, and traditional kidney disease risks. Proteinuria was nearly seven times more common in HAART-treated men than HIV− men, reflected recent eGFR decline and predicted subsequent eGFR declin

Increase in Non-AIDS Related Conditions as Causes of Death among HIV-Infected Individuals in the HAART Era in Brazil

Background. In 1996, Brazil became the first developing country to provide free and universal access to HAART. Although a decrease in overall mortality has been documented, there are no published data on the impact of HAART on causes of death among HIV-infected individuals in Brazil. We assessed temporal trends of mortality due to cardiovascular diseases (CVD), diabetes mellitus (DM) and other conditions generally not associated with HIV-infection among persons with and without HIV infection in Brazil between 1999 and 2004. Methodology/Principal Findings. Odds ratios were used to compare causes of death in individuals who had HIV/AIDS listed on any field of the death certificate with those who did not. Logistic regression models were fitted with generalized estimating equations to account for spatial correlation; co-variables were added to the models to control for potential confounding. Of 5,856,056 deaths reported in Brazil between 1999 and 2004 67,249 (1.15%) had HIV/AIDS listed on the death certificate and non-HIV-related conditions were listed on 16.3% in 1999, Increasing to 24.1% by 2004 (p<0.001) The adjusted average yearly increases were 8% and 0.8% for CVD (p<0.001), and 12% and 2.8% for DM (p<0.001), for those who had and kiki not have HIV/AIDS listed on the death certificate respectively. Similar results were found for these conditions as underlying causes of death. Conclusions/Significance. In Brazil between 1999 and 2004 conditions usually considered not to be related to HIV-infection appeared to become more likely causes of death over time than reported causes of death among individuals who had HIV/AIDS listed on the death certificate than in those who did not. This observation has important programmatic implications for developing countries that are scaling-up access to antiretroviral therapy. © 2008 Pacheco et al

The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

HIV Testing of At Risk Patients in a Large Integrated Health Care System

OBJECTIVE: Early identification of HIV infection is critical for patients to receive life-prolonging treatment and risk-reduction counseling. Understanding HIV screening practices and barriers to HIV testing is an important prelude to designing successful HIV screening programs. Our objective was to evaluate current practice patterns for identification of HIV. METHODS: We used a retrospective cohort analysis of 13,991 at-risk patients seen at 4 large Department of Veterans Affairs (VA) health-care systems. We also reviewed 1,100 medical records of tested patients. We assessed HIV testing rates among at-risk patients, the rationale for HIV testing, and predictors of HIV testing and of HIV infection. RESULTS: Of the 13,991 patients at risk for HIV, only 36% had been HIV-tested. The prevalence of HIV ranged from 1% to 20% among tested patients at the 4 sites. Approximately 90% of patients who were tested had a documented reason for testing. CONCLUSION: One-half to two-thirds of patients at risk for HIV had not been tested within our selected VA sites. Among tested patients, the rationale for HIV testing was well documented. Further testing of at-risk patients could clearly benefit patients who have unidentified HIV infection by providing earlier access to life-prolonging therapy

Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

<p>Abstract</p> <p>Background</p> <p>Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir.</p> <p>Methods</p> <p>Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status.</p> <p>Results</p> <p>50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant.</p> <p>Conclusion</p> <p>Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.</p

Contributions to early HIV diagnosis among patients linked to care vary by testing venue

<p>Abstract</p> <p>Objective</p> <p>Early HIV diagnosis reduces transmission and improves health outcomes; screening in non-traditional settings is increasingly advocated. We compared test venues by the number of new diagnoses successfully linked to the regional HIV treatment center and disease stage at diagnosis.</p> <p>Methods</p> <p>We conducted a retrospective cohort study using structured chart review of newly diagnosed HIV patients successfully referred to the region's only HIV treatment center from 1998 to 2003. Demographics, testing indication, risk profile, and initial CD4 count were recorded.</p> <p>Results</p> <p>There were 277 newly diagnosed patients meeting study criteria. Mean age was 33 years, 77% were male, and 46% were African-American. Median CD4 at diagnosis was 324. Diagnoses were earlier via partner testing at the HIV treatment center (N = 8, median CD4 648, p = 0.008) and with universal screening by the blood bank, military, and insurance companies (N = 13, median CD4 483, p = 0.05) than at other venues. Targeted testing by health care and public health entities based on patient request, risk profile, or patient condition lead to later diagnosis.</p> <p>Conclusion</p> <p>Test venues varied by the number of new diagnoses made and the stage of illness at diagnosis. To improve the rate of early diagnosis, scarce resources should be allocated to maximize the number of new diagnoses at screening venues where diagnoses are more likely to be early or alter testing strategies at test venues where diagnoses are traditionally made late. Efforts to improve early diagnosis should be coordinated longitudinally on a regional basis according to this conceptual paradigm.</p

Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption

<p>Abstract</p> <p>Background</p> <p>The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.</p> <p>Results</p> <p>The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm³{Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.</p> <p>Conclusion</p> <p>The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.</p

Frequency of human immunodeficiency virus (HIV) testing in urban vs. rural areas of the United States: Results from a nationally-representative sample

<p>Abstract</p> <p>Background</p> <p>Studies in the United States show that rural persons with HIV are more likely than their urban counterparts to be diagnosed at a late stage of infection, suggesting missed opportunities for HIV testing in rural areas. To inform discussion of HIV testing policies in rural areas, we generated nationally representative, population-based estimates of HIV testing frequencies in urban vs. rural areas of the United States.</p> <p>Methods</p> <p>Secondary analysis of 2005 and 2009 Behavioral Risk Factor Surveillance System (BRFSS) data. Dependent variables were self-reported lifetime and past-year HIV testing. Urban vs. rural residence was determined using the metropolitan area framework and Urban Influence Codes and was categorized as 1) metropolitan, center city (the most urban); 2) metropolitan, other; 3) non-metropolitan, adjacent to metropolitan; 4) non-metropolitan, micropolitan; and 4) remote, non-metropolitan (the most rural).</p> <p>Results</p> <p>The 2005 sample included 257,895 respondents. Lifetime HIV testing frequencies ranged from 43.6% among persons residing in the most urban areas to 32.2% among persons in the most rural areas (P < 0.001). Past-year testing frequencies ranged from 13.5% to 7.3% in these groups (P < 0.001). After adjusting for demographics (age, sex, race/ethnicity, and region of residence) and self-reported HIV risk factors, persons in the most remote rural areas were substantially less likely than persons in the most urban areas to report HIV testing in the past year (odds ratio 0.65, 95% CI 0.57-0.75). Testing rates in urban and rural areas did not change substantively following the 2006 Centers for Disease Control and Prevention recommendation for routine, population-based HIV testing in healthcare settings. In metropolitan (urban) areas, 11.5% (95% CI 11.2-11.8) reported past-year HIV testing in 2005 vs. 11.4% (95% CI 11.1%-11.7%) in 2009 (P = 0.93). In non-metropolitan areas, 8.7% (95% CI 8.2%-9.2%) were tested in 2005 vs. 7.7% (95% CI 7.2%-8.2%) in 2009 (P = 0.03).</p> <p>Conclusions</p> <p>Rural persons are less likely than urban to report prior HIV testing, which may contribute to later HIV diagnosis in rural areas. There is need to consider strategies to increase HIV testing in rural areas.</p

Raltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection

Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug.Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma.Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0). The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180). CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations.Approximately 50% of the CSF specimens exceeded the IC(95) levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry