Women who use antiretroviral therapy (ART) solely for the prevention of mother-to-child transmission of HIV discontinue postpartum. We hypothesized that women discontinuing ART by 6 weeks postpartum (“discontinuers”) would have elevated postpartum inflammatory biomarker levels relative to women remaining on ART postpartum (“continuers”).
Data from HIV-infected pregnant women enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 with CD4 counts >350 cells per cubic millimeter before initiating ART or first pregnancy CD4 counts >400 cells per cubic millimeter after starting ART and with available stored plasma samples at >20 weeks of gestation, delivery, and 6 weeks postpartum were analyzed. Plasma samples were tested for highly sensitive C-reactive protein, D-dimer, and interleukin-6. We used longitudinal linear spline regression to model biomarkers over time.
Data from 128 women (65 continuers and 63 discontinuers) were analyzed. All biomarkers increased from late pregnancy to delivery, then decreased postpartum (slopes different from 0, P < 0.001). Continuers had a steeper decrease in log D-dimer between delivery and 6 weeks postpartum than discontinuers (P = 0.002).
In contrast to results from treatment interruption studies in adults, both ART continuers and ART discontinuers had significant decreases in the levels of D-dimer, highly sensitive C-reactive protein, or interleukin-6 postpartum. Continuation was associated with a more rapid decline in D-dimer levels compared with discontinuation.
HIV/AIDS; pregnancy and postpartum; inflammation; antiretroviral therapy
Myeloid dendritic cell (mDC) dysfunction during HIV infection may hinder the formation of both innate and adaptive immune responses and contribute to pathogenesis. Our objective was to determine whether circulating factors during chronic HIV infection impair mDC function with respect to secretion of IL-12, a pro-Th1 cytokine, and T cell stimulatory capacity. Particular focus was placed on the effect of combination anti-retroviral therapy (cART) and the role of HIV itself on mDC function.
Monocyte-derived DC (moDC) from uninfected donors were exposed to plasma from HIV-infected individuals prior to Toll-like receptor (TLR) stimulation. Cytokine secretion was measured via cytokine bead arrays, and T cell proliferation and IFNγ secretion was evaluated following co-culture with naive CD4+ T cells. Expression of genes central to TLR-mediated signal transduction was analyzed via qRT-PCR arrays and western blot.
Exposure of moDC to plasma from untreated HIV-infected donors suppressed secretion of IL-12, and impaired Th1-skewing of CD4+ T cells. The suppressive effect was less by plasma donors receiving cART. Removal of virus from plasma did not relieve suppression, nor was IL-12 secretion decreased upon addition of HIV to control plasma. On a transcriptional level, decreased expression of IKKβ, a key regulator in the TLR/NF-kappaB signaling pathway, corresponded to suppressed cytokine secretion.
Plasma factors during chronic HIV infection impair mDC function in a manner that likely impacts the formation of immune responses to HIV, opportunistic pathogens, and vaccines. Despite partial alleviation by cART, this suppression was not directly mediated by HIV.
HIV-1; Myeloid Dendritic Cell; Innate Immunity; Toll-like receptor; IL-12; I-kappa B kinase
Measuring retention in HIV primary care is complex as care includes multiple visits scheduled at varying intervals over time. We evaluated six commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures.
Clinic-wide patient-level data from six academic HIV clinics were used for 12-months preceding implementation of the CDC/HRSA Retention in Care intervention. Six retention measures were calculated for each patient based upon scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HAB retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures to one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic.
Among 10,053 patients, 8,235 (82%) had 12-month VL measures, with 6,304 (77%) achieving suppression (VL<400 c/mL). All six retention measures were significantly associated (P<0.0001) with VL suppression (OR;95%CI, c-statistic): missed visit count (0.73;0.71–0.75,0.67), missed visit dichotomous (3.2;2.8–3.6,0.62), visit adherence (3.9;3.5–4.3,0.69), gap (3.0;2.6–3.3,0.61), visit constancy (2.8;2.5–3.0,0.63), HRSA HAB (3.8;3.3–4.4,0.59). Measures incorporating “no show” visits were highly correlated (Spearman coefficient=0.83–0.85), as were measures based solely upon kept visits (Spearman coefficient=0.72–0.77). Correlation coefficients were lower across these two groups of measures (Range=0.16–0.57).
Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard, and that selection of a retention measure may be tailored to context.
Retention in care; Adherence; Engagement in care; Viral load
Black men who have sex with men (BMSM) have the highest rates of HIV in the United States. Despite increased attention to social and sexual networks as a framework for biomedical intervention, the role of family in these networks and their relationship to HIV prevention has received limited attention.
A network sample (N=380) of BMSM (n=204) and their family members (n=176) was generated through respondent driven sampling of BMSM and elicitation of their personal networks. The proportion of personal networks that were family was calculated and weighted logistic regression was used to assess the relationship between this proportion and unprotected anal intercourse (UAI), sex-drug use (SDU) and group sex (GS); as well as intravention efforts to discourage these risk behaviors among their MSM social networks.
45.3% of respondents listed at least one family member in their close personal network. Greater family network proportion (having 2 or more family members in the close network) was associated with less SDU [adjusted odds ratio (AOR 0.38(0.17–0.87))] and participation in GS (AOR 0.25(0.10–0.67)). For intravention, BMSM with greater family proportion were more likely to discourage GS (AOR 3.83(1.56–9.43) and SDU (AOR 2.18(1.35–3.54)) among their MSM friend network. Moreover, increased male family network proportion was associated with lower HIV-risk and greater intravention than increased female network proportion.
Nearly half of BMSM have a close family member with whom they share personal information. Combination prevention interventions might be made more potent if this often overlooked component of personal networks were incorporated.
Black men who have sex with men; family network; HIV intravention; social network
Despite the major benefits of effective antiretroviral therapy (ART) on HIV-related survival, there is an ongoing need to help alleviate medication side effects related to ART use. Initial studies suggest marijuana use may reduce HIV-related symptoms, but medical marijuana use among HIV-infected individuals has not been well described.
We evaluated trends in marijuana use and reported motivations for use among 2,776 HIV-infected women in the Women’s Interagency HIV Study (WIHS) between October 1994 and March 2010. Predictors of any and daily marijuana use were explored in multivariate logistic regression models clustered by person using GEE. In 2009 participants were asked if their marijuana use was medical, “meaning prescribed by a doctor”, or recreational, or both.
Over the sixteen years of this study the prevalence of current marijuana use decreased significantly from 21% to 14%. In contrast, daily marijuana use almost doubled from 3.3% to 6.1% of all women, and from 18% to 51% of current marijuana users. Relaxation, appetite improvement, reduction of HIV-related symptoms, and social use were reported as common reasons for marijuana use. In 2009, most marijuana users reported either purely medicinal use (26%) or both medicinal and recreational usage (29%). Daily marijuana use was associated with higher CD4 cell count, quality of life, and older age. Demographic characteristics and risk behaviors were associated with current marijuana use overall, but were not predictors of daily use.
This study suggests that both recreational and medicinal marijuana use are relatively common among HIV-infected women in this U.S.
marijuana; cannabis; HIV; medicinal
Increases in multimorbidity and obesity have been noted in HIV infected populations in the current treatment era. Patterns of multimorbid disease clustering as well as the impact of obesity on multimorbidity are understudied in this population.
We examined obesity and multimorbidity patterns among 1844 HIV-infected patients in the UAB 1917 Clinic. Exploratory factor analysis (EFA) was used to identify the underlying factor structure responsible for clustering. Patterns among the resulting morbidity factors by body mass index (BMI) category were explored. Multivariable logistic regression models were fit to identify predictors of multimorbidity cluster patterns.
The prevalence of multimorbidity was 65% (1205/1844). Prevalence increased with progressive BMI categories from underweight (64%) to obese (79%). Three multimorbidity clusters were identified: “Metabolic” including hypertension (HTN), gout, diabetes mellitus, and chronic kidney disease (CKD) (range: 0.41 to 0.84; P<0.001); “Behavioral“ including mood disorders, dyslipidemia, chronic obstructive pulmonary disease (COPD), chronic ulcer disease, osteoarthritis, obstructive sleep apnea (OSA), and cardiac disorders (range: 0.32 to 0.57; P<0.001); “Substance Use” including alcohol abuse, substance abuse, tobacco abuse, and hepatitis C (range: 0.53 to 0.89; P<0.001). Obesity was associated with increased odds of multimorbidity (Obese vs. Normal BMI category: OR=1.52, 95%CI=1.15-2.00).
Three patterns of disease clustering were identified. Obesity was associated with a higher likelihood of multimorbidity. The management of multimorbidity and obesity will need to be addressed in future clinical practice guidelines to enhance long term outcomes of HIV-infected patients in the current treatment era.
Multimorbidity; Obesity; HIV; Factor Analysis; Tetrachoric
HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.
In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.
Compared with the lowest tertiles, the highest tertiles of ACR (−0.15ml/min/1.73m2, p<0.0001), IL-18 (−0.09ml/min/1.73m2, p<0.0001) and KIM-1 (−0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87).
Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.
HIV; KIM-1; NGAL; IL-18; albumin-to-creatinine ratio; cystatin C; kidney injury
Phase 0 studies can provide initial pharmacokinetics (PK) data in humans and help to facilitate early drug development, but their predictive value for standard dosing is controversial. To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of two antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standard dosing regimens.
We administered a microdose (100 μg) of 14C-labeled drug (ZDV or tenofovir disoproxil fumarate (TDF)) with or without a standard unlabelled dose (300 mg) to healthy volunteers. Both the parent drug in plasma and the active metabolite, ZDV-triphosphate (ZDV-TP) or TFV-diphosphate (TFV-DP) in PBMCs and CD4+ cells were measured by AMS.
The intracellular ZDV-TP concentration increased less than proportionally over the dose range studied (100 μg to 300 mg), while the intracellular TFV-DP PK were linear over the same dose range. ZDV-TP concentrations were lower in CD4+ cells versus total peripheral blood mononuclear cells (PBMCs), while TFV-DP concentrations were not different in CD4+ cells and PBMCs.
Our data were consistent with a rate-limiting step in the intracellular phosphorylation of ZDV but not TFV. AMS shows promise for predicting the PK of active intracellular metabolites of nucleosides, but nonlinearity of PK may be seen with some drugs.
Tenofovir diphosphate; Pharmacokinetics; Microdose
Oral rapid HIV testing has been reported to have a lower sensitivity and specificity than rapid HIV testing with whole-blood and has been associated with clusters of false positive results. Patient preference for oral rapid HIV testing compared to more invasive whole-blood fingerstick may influence the acceptance of rapid HIV testing.
To compare HIV test acceptance rates among patients routinely offered fingerstick compared to those routinely offered oral fluid screening in an urban hospital emergency department (ED).
USHER-Phase II was a single-center, prospective, randomized controlled trial that randomized subjects to either fingerstick or oral rapid HIV screening in an urban academic ED. From May 5, 2009 to January 4, 2010, eligible patients aged 18 to 75 years were invited to participate in the trial. The primary outcome measure was HIV test acceptance rate.
2,012 eligible patients were approached, of whom 1,651 (82%) consented to trial participation and enrolled. Among those enrolled 830 and 821 were randomized to the fingerstick and oral fluid arms, respectively. Acceptance of rapid HIV testing was similar in both arms; 67% (553/830) of subjects accepted fingerstick testing compared to 69% (565/821) who accepted oral (p=0.34).
Although fingerstick rapid HIV testing is more invasive than oral fluid testing, test acceptance rates did not differ. Given the option, preference should therefore be given to fingerstick testing because of its slightly superior test characteristics. System factors such as ease of staff use, necessary CLIA waivers, laboratory capacity, and HIV prevalence should also be considered.
HIV Screening; Randomized trial; OraQuick; Emergency Department
A previous study at the GHESKIO HIV clinic confirmed that highly active antiretroviral therapy (HAART) prophylaxis reduced mother-to-child transmission (MTCT) and infant mortality in Haiti. This analysis looks at maternal outcomes in this cohort after delivery.
Records of 508 HIV-positive Haitian women who delivered between1999-2005 were analyzed. We examined mortality, loss to follow-up, time to death or HAART initiation, and time of decline of CD4 count to350 cells/microliter.
170 women reached a CD4≤200 or developed clinical AIDS and were started on long-term HAART. The median CD4 count at HAART initiation was 178 (IQR 106-227). CD4 decline was stratified by CD4 at delivery to project the mean months to a CD4 of 350. With an initial CD4=350-499 cells/microliter it was 19 months (95% CI 14 - 28) while with a CD4>500 cells/microliter it was 71 months (95% CI 59 - 88). At study close 257 women remained in follow-up with loss to follow up three times less in those on HAART (3.2/100 person-years) than those not on HAART (9.8/100 person-years).
The threshold for starting treatment was often missed in HIV-infected women after delivery. Success of follow-up of women after delivery was favorably influenced by being on HAART. Women with high (>500) initial CD4 counts had a protracted time (5-7 years) before they reach a threshold CD4 count, in contrast to those with CD4<500 cells/μL. Strategies for post-partum treatment of women should be informed by the speed with which they are likely to progress.
Haiti; PMTCT; HAART
To examine how social networks influence HIV risk among U.S. racial/ethnic minority men who have sex with men (MSM) and whether the associations of social network characteristics with risk vary by race/ethnicity.
A chain-referral sample of 403 African American, 393 Asian/Pacific Islander, and 400 Latino MSM recruited in Los Angeles County, CA completed a questionnaire, which asked about their egocentric social networks, safer sex peer norms, and male anal intercourse partners. HIV-nonconcordant partnerships were those reported by respondents as serodisconcordant or where self and/or partner serostatus was unknown.
Overall, 26% of the sample reported HIV-nonconcordant unprotected anal intercourse (UAI) with a non-primary male partner in the prior six months. In a GEE logistic model that controlled for race/ethnicity, age, nativity, incarceration history, and HIV status, being in a more dense network was associated with less HIV-nonconcordant UAI (adjusted odds ratio [AOR]=0.92, 95% confidence interval [CI]=0.86–0.99, p=0.0467). In addition, the effect of safer sex peer norms on HIV-nonconcordant UAI was moderated by ego-alter closeness (p=0.0021). Safer sex peer norms were protective among those reporting “medium” or “high” ego-alter closeness (AOR=0.70, 95% CI=0.52–0.95, p=0.0213 and AOR=0.48, 95% CI=0.35–0.66, p<0.0001, respectively), but not among those reporting “low” ego-alter closeness (AOR=0.96, 95% CI=0.63–1.46, p=0.8333). The effects of density, closeness, and norms on HIV-nonconcordant UAI did not differ by race/ethnicity.
The significant association of social network characteristics with UAI point to network-level factors as important loci for both ongoing research and HIV prevention interventions among U.S. MSM of color.
Social networks; HIV risk; men who have sex with men; African American; Asian and Pacific Islander; Latino
Buprenorphine/naloxone allows the integration of opioid dependence and HIV treatment.
We conducted a prospective study in HIV-infected opioid dependent patients to investigate the impact of buprenorphine/naloxone treatment on drug use. Self-report and chart review assessments were conducted every 3 months (Quarters 1 through 4) for one year. Outcomes were buprenorphine/naloxone treatment retention, drug use, and addiction treatment processes.
Among 303 patients enrolled between July 2005 and December 2007, retention in buprenorphine/naloxone treatment was 74%, 67%, 59% and 49% during Quarters 1,2 3, and 4, respectively. Past 30 day illicit opioid use decreased from 84% of patients at baseline to 42% in retained patients over the year. Patients were 52% less likely to use illicit opioids for each quarter in treatment (OR = .66; 95% CI 0.61–0.72). Buprenorphine/naloxone doses and office visits approximated guidelines published by the United States Department of Health and Human Services. Urine toxicology monitoring was less frequent than recommended.
Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use in this treatment population.
Buprenorphine; heroin dependence; opioid-related disorders; HIV; methadone
We meta-analyzed the relationship between depression and HIV medication nonadherence to calculate the overall effect size and examine potential moderators. Overall, across 95 independent samples, depression was significantly (P < 0.0001) associated with nonadherence (r = 0.19; 95% confidence interval = 0.14 to 0.25). Studies evaluating medication adherence via interview found significantly larger effects than those using self-administered questionnaires. Studies measuring adherence along a continuum found significantly stronger effects than studies comparing dichotomies. Effect size was not significantly related to other aspects of adherence or depression measurement, assessment interval (ie, cross-sectional vs. longitudinal), sex, IV drug use, sexual orientation, or study location. The relationship between depression and HIV treatment nonadherence is consistent across samples and over time, is not limited to those with clinical depression, and is not inflated by self-report bias. Our results suggest that interventions aimed at reducing depressive symptom severity, even at subclinical levels, should be a behavioral research priority.
adherence; compliance; depression; HIV/AIDS; meta-analysis
The provision of food supplementation to food insecure patients initiating antiretroviral therapy may improve adherence to medications.
A home-based adherence support program at 8 government clinics assessed patients for food insecurity. 4 clinics provided food supplementation and 4 acted as controls. The analysis compared adherence (assessed by medication possession ratio [MPR]), CD4, and weight gain outcomes among food insecure patients enrolled at the food clinics to those of controls.
Between May 1, 2004 and March 31, 2005, 636 food insecure adults were enrolled. Food supplementation was associated with better adherence to therapy. 258 of 366 (70%) of patients in the food group achieved an MPR of 95% or greater versus 79 of 166 (48%) among controls (relative risk, RR=1.5; 95%CI:1.2-1.8). This finding was unchanged after adjustment for sex, age, baseline CD4 count, baseline WHO stage, and baseline hemoglobin. We did not observe a significant effect of food supplementation on weight gain or CD4 cell response.
This analysis suggests that providing food to food insecure patients initiating ART is feasible and may improve adherence to medication. A large randomized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy.
HIV; adherence; food supplementation; food insecurity; Zambia
The incidence of and risk factors for falls in human immunodeficiency (HIV)-1-infected persons are unknown.
Fall history during the prior 12 months, medical diagnoses, and functional assessments were collected on HIV-infected persons 45 to 65 years of age receiving effective antiretroviral therapy. Fall risk was evaluated using univariate and multivariate regression analyses.
Of 359 subjects, 250 persons (70%) reported no falls, 109 (30%) had ≥1 fall; 66 (18%) were recurrent fallers. Females, Caucasians, and smokers were more like to be recurrent fallers (p≤0.05). HIV-related characteristics including current and nadir CD4 T-cell count, estimated HIV duration, and Veterans Aging Cohort Study Index scores were not predictors of falls (all p≥0.09); didanosine recipients were more likely to be recurrent fallers (p=0.04). The odds of falling increased 1.7 for each comorbidity and 1.4 for each medication (p<0.001), and were higher in persons with cardiovascular disease, hypertension, dementia, neuropathy, arthritis, chronic pain, psychiatric disease, frailty or disability (all OR≥ 1.8; p≤0.05). Beta-blockers, antidepressants, anti-psychotics, sedatives, and opiates were independently associated with falling (all OR ≥2.7; p≤0.01). Female gender, diabetes, antidepressants, sedatives, opiates, didanosine, exhaustion, weight loss, and difficulty with balance were the most significant predictors of falls in logistic regression (all OR ≥2.5; p≤0.05).
Middle-aged HIV-infected adults have high fall risk. Multiple comorbidities, medications, and functional impairment were predictive of falls, but surrogate markers of HIV infection or an HIV-specific multimorbidity index were not. Fall risk should be assessed routinely as part the care of HIV-infected persons.
HIV; aging; accidental falls
Low bone mineral density (BMD) has been reported among 10–54% of HIV-infected adolescents in developed countries. We studied the prevalence and predictors of low BMD among HIV-infected Thai adolescents receiving antiretroviral therapy.
A cross-sectional study of lumbar spine (L2–L4) BMD as measured by dual-energy X-ray absorptiometry (DXA) in Thai HIV-infected adolescents aged 12–20 years was performed. The BMD Z-score was analyzed using age-matched healthy Thai children as a reference. Serum 25-hydroxyvitamin D (25-OHD) was performed. Osteopenia was defined as BMD Z-score≤ −2.
From October 2010 to February 2011, 101 adolescents, 50% male, with a median age of 14.3 (range, 13.0–15.7) years were enrolled. The median (IQR) current CD4 T-cell count was 646 (506–796) cells/mm3 and 90% had plasma HIV-1 RNA <50 copies/ml. The mean BMD among HIV-infected adolescents and controls were 0.855 and 0.980 g/cm2(P<0.001). The median (IQR) L2–L4 spine BMD Z-score was −1.0 (−1.9 to −0.1), of which 24% had BMD Z-score ≤ −2.0. The median (IQR) of 25-OHD level was 24.8 (20.0–31.4) ng/ml, of which 25% had vitamin D level < 20 ng/ml. In multivariate analysis, the height for age Z-score <−1.5 (adjusted odds ratio (aOR) 6.2; 95% CI 2.2–17.7) and history of WHO clinical stage 4 prior to ART (aOR 3.7; 95%CI 1.3–10.7) were significantly associated with osteopenia.
One-fourth of HIV-infected Thai adolescents have osteopenia. Children with history of advanced- staging or having low height for age are at risk of osteopenia. Preventive measures to prevent osteopenia should be incorporated in routine care for these adolescents.
Bone mineral density; HIV-infected adolescents; vitamin D deficiency; osteopenia
We evaluated the longitudinal association of alcohol use with immunological response to combination antiretroviral therapy (ART) among HIV infected individuals.
This was a prospective cohort study of individuals initiating ART. Participants underwent an Audio Computer-Assisted Self Interview querying drug and alcohol use within 6 months of treatment. Immunological response to ART was defined by CD4 T-cell count (CD4). Primary independent variables were self-reported number of drinks consumed per drinking day (quantity) and days of alcohol consumption in a typical week (frequency). We used linear mixed effects models to quantify the association between CD4 T-cell count and alcohol quantity and frequency and Cox proportional hazards models to estimate the relative hazard of an increase 100, 150 and 200 CD4 cells/mm3 per additional drink per drinking day. Analyses were stratified by gender. Viral suppression was examined as a time-varying covariate.
Between 2000-2008, 1107 individuals were eligible for inclusion in this study. There was no statistically significant difference in CD4 T-cell count by average drinks per drinking day at any frequency of alcohol use irrespective of gender or viral suppression. Similarly, we found no difference in the hazard ratio for drinks per drinking day within the categories of drinking frequency for time to CD4 T-cell count increase of 100, 150 and 200 cells/mm3, respectively.
Among individuals initiating antiretroviral therapy (ART) the benefits of therapy and viral suppression on the immune system outweigh detrimental effects of alcohol, reinforcing the importance of initiating ART and ensuring adequate adherence to therapy.
HIV; alcohol; Immune Response; CD4 T-CELL COUNT; antiretroviral therapy
Alcohol; self-report; phosphatidylethanol; biomarker; bias; sub-Saharan Africa
To understand how regional body composition affects bone mineral density (BMD) in HIV-infected and uninfected women.
Dual energy X-ray absorptiometry was used to measure regional lean and fat mass and BMD at lumbar spine (LS), total hip (TH), and femoral neck (FN) in 318 HIV-infected and 122 HIV-uninfected Women's Interagency HIV Study participants at baseline and 2 and 5 years later. Total lean and fat mass were measured using bioimpedance analysis. Multivariate marginal linear regression models assessed the association of HIV status and body composition on BMD change.
Compared to HIV-uninfected women, HIV-infected women were older (44 vs. 37 yrs), more likely to be HCV-infected (32% vs. 14%), and post-menopausal (26% vs. 3%), and had lower baseline total fat mass, trunk fat and leg fat. In multivariate models, increased total lean mass was independently associated with increased BMD at LS, TH and FN and total fat mass was associated with increased BMD at TH and FN (all p<0.05). When total fat was replaced in multivariate models with trunk fat and leg fat, increased trunk fat (and not leg fat) was associated with increased TH and FN BMD (p<0.001).
Total fat and lean mass are strong, independent predictors of TH and FN BMD, and lean mass was associated with greater LS BMD. Regardless of HIV status, greater trunk fat (and not leg fat) was associated with increased TH and FN BMD, suggesting that weight bearing fat may be a more important predictor of BMD in the hip.
Body composition; fat redistribution; bone mineral density; HIV; women
Translocation of gastrointestinal bacteria in HIV-infected individuals is associated with systemic inflammation, HIV progression, mortality, and co-morbidities. HIV-infected individuals are also susceptible to fungal infection and colonization, but whether fungal translocation occurs and influences HIV progression or co-morbidities is unknown.
Serum (1→3)-β-D-glucan was measured by a Limulus Amebocyte Lysate assay (Fungitell®) in 132 HIV-infected outpatients. Selected plasma cytokines and markers of peripheral T-cell activation were measured. Pulmonary function testing and Doppler-echocardiography were performed. Relationship of high (≥40pg/ml) and low (<40pg/ml) levels of (1→3)-β-D-glucan with HIV-associated variables, inflammation markers, and pulmonary function and pulmonary hypertension measures were determined.
Forty-eight percent had detectable (1→3)-β-D-glucan, and 16.7% had high levels. Individuals with high (1→3)-β-D-glucan were more likely to have CD4 counts below 200 cells/μl (31.8% vs. 8.4%, p=0.002), had higher log10 HIV viral levels (2.85 vs. 2.13 log copies/ml, p=0.004), and were less likely to use ART (68.2% vs. 90.0%, p=0.006). Plasma IL-8 (p=0.033), TNF-α (p=0.029), and CD8+CD38+ (p=0.046) andCD8+HLA-DR+ (p=0.029) were also increased with high levels. Abnormalities in diffusing capacity (p=0.041) and in pulmonary artery pressures (p=0.006 for pulmonary artery systolic pressure and 0.013 for tricuspid regurgitant velocity) were more common in those with high (1→3)-β-D-glucan.
We found evidence of peripheral fungal cell wall polysaccharides in an HIV-infected cohort. We also demonstrated an association between high serum (1→3)-β-D-glucan, HIV-associated immunosuppression, inflammation, and cardiopulmonary co-morbidity. These results implicate a new class of pathogen in HIV-associated microbial translocation and suggest a role in HIV progression and co-morbidities.
HIV; COPD; (1→3)-β-D-glucan; pulmonary hypertension; emphysema; inflammation
In women, genital HIV-1 RNA levels predict the risk of HIV-1 transmission independent of plasma viral load. To better understand the factors that contribute to genital HIV-1 shedding, we evaluated the relationships between genital and plasma cytokine concentrations and HIV-1 RNA levels. Vaginal, but not plasma, levels of interferon gamma-induced protein 10 (IP-10) were significantly associated with vaginal viral load, independent of plasma viral load. Thus, efforts to decrease HIV-1 transmission must take into account the role of local inflammation, which is not necessarily reflected in plasma measurements.
HIV-1; inflammation; cytokine; genital; shedding; transmission
In the United States (US), kidney dysfunction is prevalent in almost 30% of HIV-infected patients and is an independent predictor of mortality. Proteinuria and elevated serum cystatin C (eCysC) are used as markers of kidney disease in the general population; however, the prevalence of these markers in HIV-infected adolescents is largely unknown.
This study includes 304 HIV-infected adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort, an observational study of adolescents recruited from 13 US cities. Clinical and demographic characteristics of participants were evaluated as correlates of proteinuria, a urine protein to creatinine ratio (UP/Cr) of ≥200 mg/g. Select univariate predictors were assessed to determine the association with urinary protein excretion and serum cystatin C in multivariable linear regression models and proteinuria and elevated serum cystatin C (eCysC ≥ 75th percentile) in multivariable logistic regression models.
Overall, 19.1% of the participants had proteinuria while 23.7% had an eCysC. Low CD4+ T-lymphocyte counts (<200 cells/mm3) were significantly associated with a greater UP/Cr in linear models and with proteinuria in logistic regression models. CD4+ T-lymphocyte counts <500 cells/mm3 were significantly associated with a greater serum cystatin C concentration in linear models and with eCysC in logistic regression models.
Proteinuria among HIV-infected adolescents in REACH was approximately two-fold greater than healthy US adolescents. Both proteinuria and eCysC are associated with CD4+ T-lymphocyte counts. Further studies investigating early markers of kidney disease and the association with immune status and inflammation in adolescents are needed.
HIV; adolescent; kidney; CD4+ T-cells; proteinuria; serum cystatin C
The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function.
We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and SIV-infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239.
There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down-regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells.
Early initiation of ART prevented virus induced damage and did not impede mucosal or systemic immune functions.
antiretroviral therapy; mucosal immunity; peripheral immunity; SIV
HIV infections increased 48% among young, Black men who have sex with men (MSM) in the United States between 2006–2009. Incomplete understanding of this trend undermines prevention strategy development. We investigated a sexual network to characterize the risk environment in which young, Black MSM acquire HIV.
Persons reported to the state following diagnosis of HIV or syphilis were included, along with sexual partners. We used network mapping alongside descriptive and bivariate statistics to characterize network connections. Generalized linear models assessed predictors of having untraceable sex partners.
The network included 398 individuals and 419 sexual relationships. Three-quarters were Black (n=299); 92% were MSM. Median age at first network appearance was 26 years and decreased over time (P<0.001). HIV prevalence was at least 29% (n=117); serostatus was unknown for 47% of the network, either because they were untraceable (n=150) or refused HIV testing (n=39). One in 5 network members diagnosed with HIV had a subsequent incident sexually transmitted infection. In multivariable models, one-time encounters increased the risk of having an untraceable partner (risk ratio 4.51, 95% CI, 2.27, 8.97), while being acutely HIV infected at diagnosis reduced it (RR 0.27, 95% CI, 0.08, 0.89).
HIV prevalence in this sexual network of young, Black MSM rivals that of sub-Saharan Africa, reflecting dramatically increased risk of acquiring HIV from the moment one entered the network. Prevention efforts for this population must consider the effect of sexual networks on HIV risk, and find ways of leveraging network structure to reduce transmission.
HIV; African-American; men who have sex with men; sexual networks