Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314.

BACKGROUND: Chronic inflammation in treated HIV infection is associated with mortality and atherosclerotic cardiovascular disease (ASCVD). We evaluated the safety and potential efficacy of low-dose methotrexate (LDMTX) in treated HIV. METHODS: This was a phase 2 randomized, double-blind, multicenter trial in adults ≥40 years old with treated HIV, with CD4+ T-cell count ≥400 cells/µL and with/at increased risk for ASCVD. Participants received LDMTX (5-15 mg/week) or placebo (plus folic acid) for 24 weeks and were followed for an additional 12 weeks. Primary endpoints were safety and brachial artery flow-mediated dilation (FMD). RESULTS: The 176 participants (90% male) had a median (Q1, Q3) age of 54 (49, 59) years. LDMTX was associated with decreases in CD4+ T cells at week 24 and CD8+ T cells at weeks 8, 12, and 24. Eleven participants (12.8%) experienced safety events in the LDMTX group vs 5 (5.6%) in placebo (Δ = 7.2%, upper 1-sided 90% CI, 13.4%; Pnoninferiority = .037). Week 24 change in FMD was 0.47% with LDMTX and 0.09% with placebo (P = .55). No inflammatory markers changed differentially with LDMTX compared to placebo. CONCLUSIONS: Adults with HIV and increased ASCVD risk treated with LDMTX had more safety events than with placebo, but the prespecified noninferiority margin of 15% was not exceeded. LDMTX had no significant effect on endothelial function or inflammatory biomarkers but was associated with a significant decrease in CD8+ T cells. The balance of risks and potential benefits of LDMTX in this population will require additional investigation. CLINICAL TRIALS REGISTRATION: NCT01949116.

Age Differences by Sex in Antiretroviral-Naïve Participants: Pooled Analysis from Randomized Clinical Trials.

Age and sex effects on antiretroviral therapy (ART) response are not well elucidated. Our pooled analysis of 40 randomized clinical trials measured the association of age and sex on CD4+ T cell count changes and virologic suppression using multivariable regression modeling. The average increase in CD4+ T cell count from baseline to week 48 was 17.3 cells/mm3 lower and clinically insignificant (95% confidence interval -30.8 to -3.8) among women ages ≥ 50 years (n = 573), compared to women ≤ 35 years (n = 3,939). Results were similar for men. Virologic suppression odds were 60% and 21% times greater among participants ≥50 years compared to ≤35 years, in women and men, respectively. In both sexes, larger increases in CD4+ T cell count changes were observed in younger, compared to older, participants; however, virologic suppression was higher in older, compared to younger, participants suggesting a non-sex-specific age effect response to ART.

Managing the Personal Side of Health Care among Patients with HIV/AIDS.

The study describes the HIV care providers' sociodemographic and medical practice characteristics and the health care services offered to patients during medical care encounters in Houston/Harris County, Texas. We used data from the pilot cycle of the Centers for Disease Control and Prevention Medical Monitoring Project Provider Survey conducted in June to September 2009. The average age and HIV care experience of the providers were 46.7 and 11.7 years, respectively, and they provided care to an average of 113 patients monthly. The average proportion of HIV-infected patients seen per month by race/ethnicity was 43.3% for blacks, 28.5% for whites, 26.6% for Hispanics, 1.3% for Asians, and 0.6% for other races. A total of 67% of providers offered HIV testing to all patients 13 to 64 years of age. Most HIV care providers (73.9%) reported that patients in their practices sought HIV care only after experiencing symptoms. Understanding the HIV care delivery system from providers' perspectives may help enhance support services, patients' ongoing care and retention, leading to improved health outcomes.

Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People.

HIV-1-infected persons have increased risk of serious non-AIDS events (SNAEs) despite suppressive antiretroviral therapy. Increased circulating levels of soluble CD14 (sCD14), soluble CD163 (sCD163), and interleukin-6 (IL-6) at a single time point have been associated with SNAEs. However, whether changes in these biomarker levels predict SNAEs in HIV-1-infected persons is unknown. We hypothesized that greater decreases in inflammatory biomarkers would be associated with fewer SNAEs. We identified 39 patients with SNAEs, including major cardiovascular events, end stage renal disease, decompensated cirrhosis, non-AIDS-defining malignancies, and death of unknown cause, and age- and sex-matched HIV-1-infected controls. sCD14, sCD163, and IL-6 were measured at study enrollment (T1) and proximal to the event (T2) or equivalent duration in matched controls. Over ∼34 months, unchanged rather than decreasing levels of sCD14 and IL-6 predicted SNAEs. Older age and current illicit substance abuse, but not HCV coinfection, were associated with SNAEs. In a multivariate analysis, older age, illicit substance use, and unchanged IL-6 levels remained significantly associated with SNAEs. Thus, the trajectories of sCD14 and IL-6 levels predict SNAEs. Interventions to decrease illicit substance use may decrease the risk of SNAEs in HIV-1-infected persons.

Frequency and Determinants of Preventive Care Counseling by HIV Medical Care Providers during Encounters with Newly Diagnosed and Established HIV-Infected Patients.

This study evaluates the frequency and determinants of preventive care counseling by HIV medical care providers (HMCPs) during encounters with newly diagnosed and established HIV-infected patients. Data used were from a probability sample of HMCPs in Houston/Harris County, Texas, surveyed in 2009. Overall, HMCPs offered more preventive care counseling to newly diagnosed than the established patients (adjusted odds ratio [AOR] = 7.28; 95% confidence interval [CI] = 2.86-16.80). They were more likely to counsel newly diagnosed patients than the established ones on medication and adherence (AOR = 14.70; 95% CI = 1.24-24.94), HIV risk reduction (AOR = 5.91; 95% CI = 0.48-7.13), and disease screening (AOR = 7.20; 95% CI = 0.72-11.81). HIV medical care providers who were less than 45 years of age, infectious disease specialists, and had less than 30 minutes of encounter time were less likely to counsel patients regardless of the status. Our findings suggest the need for HMCPs to improve their preventive care counseling efforts, in order to help patients build skills for adopting and maintaining safe behavior that could assist in reducing the risk of HIV transmission.

Obesity Among HIV-Infected Adults Receiving Medical Care in the United States: Data From the Cross-Sectional Medical Monitoring Project and National Health and Nutrition Examination Survey.

Our objective was to compare obesity prevalence among human immunodeficiency virus (HIV)-infected adults receiving care and the U.S. general population and identify obesity correlates among HIV-infected men and women.Cross-sectional data was collected in 2009 to 2010 from 2 nationally representative surveys: Medical Monitoring Project (MMP) and National Health and Nutrition Examination Survey (NHANES).Weighted prevalence estimates of obesity, defined as body mass index ≥30.0 kg/m, were compared using prevalence ratios (PR, 95% confidence interval [CI]). Correlates of obesity in HIV-infected adults were examined using multivariable logistic regression.Demographic characteristics of the 4006 HIV-infected adults in MMP differed from the 5657 adults from the general U.S. population in NHANES, including more men (73.2% in MMP versus 49.4% in NHANES, respectively), black or African Americans (41.5% versus 11.6%), persons with annual incomes <$20,000 (64.5% versus 21.9%), and homosexuals or bisexuals (50.9% versus 3.9%). HIV-infected men were less likely to be obese (PR 0.5, CI 0.5-0.6) and HIV-infected women were more likely to be obese (PR1.2, CI 1.1-1.3) compared with men and women in the general population, respectively. Among HIV-infected women, younger age was associated with obesity (<40 versus >60 years). Among HIV-infected men, correlates of obesity included black or African American race/ethnicity, annual income >$20,000 and <$50,000, heterosexual orientation, and geometric mean CD4+ T-lymphocyte cell count >200 cells/µL.Obesity is common, affecting 2 in 5 HIV-infected women and 1 in 5 HIV-infected men. Correlates of obesity differ for HIV-infected men and women; therefore, different strategies may be needed for the prevention and treatment.

A mixed-methods approach to understanding barriers to postpartum retention in care among low-income, HIV-infected women.

Optimal retention in HIV care postpartum is necessary to benefit the health and wellbeing of mothers and their infants. However, postpartum retention in HIV care among low-income women is suboptimal, particularly in the Southern United States. A mixed-methods study was conducted to identify factors associated with postpartum retention in care among HIV-infected women. Participants (n=35) were recruited during pregnancy at two county clinics and completed self-report demographic and psychosocial surveys. Twenty-two women who returned for a postpartum appointment completed a semi-structured interview about lifestyle factors and retention in care. Of the participants enrolled at baseline, 71.4% completed a follow-up with an obstetrician (OB), while 57.1% completed a follow-up with a primary care physician (PCP). High CD4 count at delivery, low viral load at baseline, low levels of depression, high interpersonal social support, and fewer other children were significantly associated with completion of postpartum follow-up. Barriers and facilitators to retention identified during qualitative interviews included competing responsibilities for time, lack of social support outside of immediate family members, limited transportation access, experiences of institutionalized stigma, knowledge about the benefits of adherence, and strong relationships with healthcare providers. OB and PCP follow-up postpartum was suboptimal in this sample. Findings underscore the importance of addressing depressive symptoms, social support, viral suppression, competing responsibilities for time, institutionalized stigma, and transportation issues in order to reduce the barriers that inhibit women from seeking postpartum HIV care.

System and Patient Barriers to Care among People Living with HIV/AIDS in Houston/Harris County, Texas: HIV Medical Care Providers' Perspectives.

In the United States, a considerable number of people diagnosed with HIV are not receiving HIV medical care due to some barriers. Using data from the Medical Monitoring Project survey of HIV medical care providers in Houston/Harris County, Texas, we assessed the HIV medical care providers' perspectives of the system and patient barriers to HIV care experienced by people living with HIV/AIDS (PLWHA). The study findings indicate that of the 14 HIV care barriers identified, only 1 system barrier and 7 patient barriers were considered of significant (P ≤ .05) importance, with the proportion of HIV medical care providers' agreement to these barriers ranging from 73.9% (cost of health care) to 100% (lack of social support systems and drug abuse problems). Providers' perception of important system and patient barriers varied significantly (P ≤ .05) by profession, race/ethnicity, and years of experience in HIV care. To improve access to and for consistent engagement in HIV care, effective intervention programs are needed to address the barriers identified especially in the context of the new health care delivery system.

Predictive factors for loss to postpartum follow-up among low income HIV-infected women in Texas.

Guidelines for HIV primary care include visits every 3 months (up to 6 months in those with stable HIV). During pregnancy, women with HIV commonly attend once weekly to once monthly visits; however, after delivery, many are lost to follow-up. Our goal was to assess the frequency of loss to primary care follow-up postpartum and to identify predictors of loss to care. A retrospective chart review of HIV-infected women in a Houston prenatal program was done. Optimal care was defined as one visit to HIV primary care providers (PCPs) every 6 months within the first year after delivery, and loss to follow-up as no visits within the first postpartum year. Multivariate logistic regression analysis was used to identify factors associated with loss to follow-up. Charts (n=213) were analyzed for follow-up with PCPs. The loss to follow-up rate was 39% in the first postpartum year. Associated factors were younger age, black race, late entry to prenatal care, and no plans for contraception. Predictors of loss to primary care after pregnancy can be used to identify specific subpopulations of pregnant women at highest risk for falling out of care.