Search

Introduction: Reduced estimated glomerular filtration rate (eGFR) is associated with increased risk of cardiovascular disease among people living with HIV (PLWH). It is unclear whether eGFR equations incorporating cystatin C (CysC) measurements are more predictive of preclinical cardiovascular disease than those using only creatinine (Cr)., Objectives: The study aimed to determine which of the 3 Chronic Kidney Disease Epidemiology (CKD-EPI) eGFR equations is most associated with carotid intima media thickness (CIMT) and coronary artery calcium (CAC) score., Methods: This cross-sectional analysis of pooled data from 3 large cohorts compared the associations between the 3 CKD-EPI eGFR equations (Cr, CysC, and Cr-CysC) with CIMT and CAC score using multivariable regression analysis. eGFR and CIMT were analyzed as continuous variables. CAC scores were analyzed as a binary variable (detectable calcification versus nondetectable) and as a log10 Agatston score in those with detectable CAC., Results: Thousand four hundred eighty-seven participants were included, and of these 910 (562 HIV+ and 348 HIV-) had CIMT measurements and 366 (296 HIV+ and 70 HIV-) had CAC measurements available. In HIV- participants, GFR estimated by any CKD-EPI equation did not significantly correlate with CIMT or CAC scores. When PLWH were analyzed separately including HIV-specific factors, only GFR estimated using Cr-Cys C correlated with CIMT [β= -0.90, 95% CI: (-1.67 to -0.13) μm; P = 0.023]. Similarly, eGFR correlated with Agatston scores only when using cystatin C-based eGFR [β= -8.63, 95% CI: (-16.49 to -0.77) HU; P = 0.034]. Associations between other eGFR formulas and CAC did not reach statistical significance., Conclusions: In PLWH, preclinical atherosclerosis may be more closely correlated with eGFR using formulae that incorporate CysC measurements than Cr alone.

Objective: To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration after treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals., Setting: Single-arm, 24-week, open-label clinical trial., Methods: HIV-infected individuals on antiretroviral therapy ≥1 year with plasma HIV RNA ≤50 copies per milliliter and below-normal cognitive performance [defined as age-, sex-, and education-adjusted NP performance (NPZ) <-0.5 in a single cognitive domain or in global performance] were enrolled. Changes over 24 weeks were assessed for global and domain-specific NPZ scores, plasma markers of monocyte/macrophage activation [neopterin, soluble (s)CD14, and sCD163] quantified by ELISA, and CCR2 and CCR5 expression on monocytes, and T cells measured by flow cytometry., Results: Seventeen of 20 enrolled participants completed the study. Improvements over 24 weeks were observed in global NPZ [median change (Δ) = 0.24; P = 0.008], and in cognitive domains of attention (Δ0.23; P = 0.011) and working memory (Δ0.44; P = 0.017). Plasma levels of sCD163, sCD14 and neopterin decreased significantly (P's < 0.01). CCR2 and CCR5 monocyte expression remained unchanged; however, CCR5 levels on CD4 and CD8 T cells and CCR2 expression on CD4 T cells increased (P's < 0.01)., Conclusions: CVC given over 24 weeks was associated with improved NP test performance and decreased plasma markers of monocyte immune activation in virally suppressed, HIV-infected participants. These data potentially link changes in monocyte activation to cognitive performance. Further study of CVC for HIV cognitive impairment in a randomized controlled study is warranted.

Background: Data on changes in metabolic syndrome (MetS) status in HIV-infected adults on antiretroviral therapy (ART) are limited., Methods: MetS was assessed at ART initiation and every 48 weeks on ART in ART-naive HIV-infected individuals from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) cohort. MetS, defined using the Adult Treatment Panel III criteria, required at least 3 of the following: elevated fasting glucose, hypertension, elevated waist circumference, elevated triglycerides, low high-density lipoprotein (HDL) cholesterol. Prevalence of MetS and the individual criteria were compared between ART initiation and during follow-up using McNemar test., Results: At ART initiation, 450 (20%) ALLRT participants had MetS. After 96 weeks of ART, 37% of the 411 with MetS at ART initiation and with available data at this time point did not meet the MetS criteria. Among these participants, there was a dramatic decline in the proportion with low HDL (95% versus 26%, P < 0.0001). Among the 63% who continued to meet MetS criteria at week 96, the proportion with ≥4 criteria was higher at week 96 compared to at the time of ART initiation (48% versus 40%, P = 0.03); at week 96, the proportion with high triglycerides was greater (87% versus 69%, P < 0.0001) as was the proportion with high glucose (59% versus 42%, P < 0.0001)., Conclusions: One in 5 ART-naive subjects met criteria for MetS at ART initiation. Although more than half of these individuals continued to have MetS after 96 weeks of ART, 37% with MetS at ART initiation no longer met criteria for MetS; this decrease was driven largely by increases in HDL cholesterol.

Background: Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease and diabetes, many of which are associated with HIV and antiretroviral therapy (ART). We examined prevalence and incidence of MetS and risk factors for MetS in ART-naive HIV-infected individuals starting ART., Methods: MetS, defined by the Adult Treatment Panel III criteria, was assessed at and after ART initiation in HIV-infected individuals who enrolled in selected AIDS Clinical Trials Group trials and were followed long-term after these trials as part of the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. Cox proportional hazards models were used to examine risk factors of incident MetS. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) are reported., Results: At ART initiation, the prevalence of MetS was 20%. After ART initiation, the incidence of MetS was 8.5 per 100 person-years. After adjusting for demographics and body mass index, the risk of MetS was decreased for CD4+ T-cell counts >50 cells per cubic millimeter (aHR = 0.62, 95% CI = 0.43 to 0.90 for CD4 >500), and the risk was increased for HIV-1 RNA >400 copies per milliliter (aHR = 1.55 (95% CI = 1.25 to 1.92) and use of a protease-inhibitor (PI)-based regimen [relative to no PI use, aHR = 1.25 (95% CI = 1.04 to 1.51) for any PI use]., Conclusions: In HIV-infected individuals on ART, virologic suppression and maintenance of high CD4+ T-cell counts may be potentially modifiable factors that can reduce the risk of MetS. The effect of MetS on the risk of cardiovascular disease and diabetes needs to be evaluated.

Objective: The objective of this study was to investigate the incidence, demographics, HIV subtype, and genotypic resistance of acute HIV infections in a high-risk Thai population., Methods: Between March 2006 and September 2007, 6426 stored samples at the Thai Red Cross Anonymous Clinic were screened for acute HIV infection by 2 methods: pooled nucleic acid testing (NAT) of fourth-generation enzyme immunoassay (EIA)-negative samples (n = 5402) and subsequent first-generation EIA testing of fourth-generation EIA-positive samples (n = 1024)., Results: Eleven acute HIV-infected subjects were identified by pooled NAT (n = 7) and serial EIA (n = 4). Mean age was 28 years; 9 were male; and 60% were men who have sex with men. Median HIV RNA was 99,601 copies per milliliter (log10 viral load (VL) = 5.00). Eight samples could be genotyped: 6, CRF01&#95;AE; 1, subtype B; and 1, CRF01&#95;AE/B recombinant. No resistance to antiretroviral therapy was found. The HIV incidence per 100 person-years, calculated from the pooled, antibody-negative samples, was 2.7% (95% confidence interval, 2.2%-4.3%)., Conclusions: This is the first report of antibody-negative, NAT-positive, acute HIV infection in Thailand. The majority were men who have sex with men, which reflects the current epidemic in Thailand and justifies prevention programs aimed at this group. This high-risk population may be suitable for future studies on acute HIV infection, HIV treatment, vaccine, and prevention of onward transmission strategies.

Background: Subcutaneous limb fat loss continues to be one the most troubling side effects of long-term antiretroviral regimens. Nucleoside analogues and protease inhibitors (PIs) have been linked to the development of this complication., Methods: We evaluated the effects of nucleoside-sparing and PI-sparing regimens on fat distribution, bone mineral density, and metabolic parameters in 62 subjects, who were not selected for lipoatrophy, with advanced HIV (nadir CD4 count or=80,000 copies/mL) and an undetectable HIV viral load. Participants were randomized to switch their initial successful antiretroviral regimen to open-label lopinavir/ritonavir (LPV/r) at a dose of 533/133 mg twice a day and efavirenz (EFV) at a dose of 600 mg/d (the nucleoside-sparing arm) versus EFV and 2 nucleoside analogues (the PI-sparing arm)., Findings: At week 48, the median change in limb fat in the nucleoside-sparing arm was 562 g (6%, interquartile range [IQR]: -218-1186 g) versus a loss of -242 g (-4%, IQR: -539-452 g) in the nucleoside-containing PI-sparing arm (P = 0.086). At the time of last observation (median = 102 weeks, IQR: 73-152 weeks), a median gain of 782 g (10%, IQR: -380-1168 g) of limb fat was noted in the nonnucleoside arm (n = 22) versus a loss of 850 g (-15%, IQR: -1270 to -526 g) in the nucleoside-containing arm (n = 25; P = 0.002)., Interpretation: The switch to a nucleoside-sparing combination antiretroviral regimen (LPV/r + EFV) was associated with significant improvement in limb fat. These results provide additional evidence that nucleoside analogues are important in the progressive limb fat loss that characterizes antiretroviral treatment and that switching medications can significantly improve this complication. This option has to be carefully balanced with the potential to increase serum lipid levels and the trend to increase virologic failure.

Recent studies of pregnant women and animal models have raised concerns regarding potentially serious mitochondrial toxicity-related side effects in infants born to mothers who received nucleoside reverse transcriptase inhibitors (NRTIs) during their pregnancy to prevent HIV-1 perinatal transmission. The aim of this study was to assess mitochondrial DNA (mtDNA) content of cord blood and placenta in HIV-infected pregnant women receiving NRTI compared with HIV-negative women, hypothesizing that placenta and cord blood mtDNA copies per cell would be decreased in women on NRTI therapy. Immediately following delivery, placenta and cord blood were obtained from eight HIV-infected pregnant women on NRTIs and five HIV-negative women. Assessment of mtDNA copies per cell was accomplished by quantitative real-time PCR. The mean mtDNA copies per cell from the placenta of the HIV-infected women compared with HIV-negative women was 152 +/- 119 and 880 +/- 136 ( =.0016), respectively. Similarly, the mean mtDNA copies per cell from the cord blood of the HIV-positive women compared with HIV-negative women was 144 +/- 101 and 865 +/- 331 ( =.0026), respectively. There was a statistically significant decrease in mtDNA copies per cell in placenta and cord blood between the HIV-infected women on NRTIs compared with HIV-negative women. Further studies are needed to better understand the morbidity to infants and mothers treated with NRTI to prevent vertical transmission of HIV.