The contribution of syndemic conditions to cardiovascular disease risk.

The syndemic conditions of low education, childhood maltreatment, depression, HIV, alcohol and cocaine use, and obesity have been established as independent risk factors for cardiovascular risk, but research examining the association between syndemic conditions and cardiovascular risk in high-risk populations is lacking. A total of N = 503 participants underwent an ultrasound of the carotid artery to assess for atherosclerotic plaque. Participants, HIV-infected (n = 202) and HIV-uninfected (n = 301) with and without a history of cocaine use, were a mean age of 36.13 years (SD = 9.51); 50% were male, and 62% were African-American. Each syndemic condition was associated with 8% greater odds of atherosclerotic plaque (OR = 1.08), 9% greater odds of systolic blood pressure (OR = 1.09), and 10% greater odds of diastolic blood pressure (OR = 1.10). Multilevel research, interventions, and public policy initiatives are needed to activate stakeholders at each level to maximize their impact at a community level among populations with high rates of syndemic conditions.

Blue Monday: Co-occurring Stimulant Use and HIV Persistence Predict Dysregulated Catecholamine Synthesis.

BACKGROUND: This longitudinal study examined whether co-occurring stimulant use and HIV disease processes predicted greater risk for depression via dysregulated metabolism of amino acid precursors for neurotransmitters. METHODS: In total, 110 sexual minority men (ie, gay, bisexual, and other men who have sex with men) living with HIV who had biologically confirmed recent methamphetamine use were enrolled in a randomized controlled trial. The kynurenine/tryptophan (K/T) and phenylalanine/tyrosine (P/T) ratios were measured over 15 months to index dysregulated metabolism of amino acid precursors for serotonin and catecholamines. Markers of gut-immune dysregulation such as lipopolysaccharide binding protein and soluble CD14 (sCD14), HIV persistence in immune cells (ie, proviral HIV DNA), and stimulant use were examined as predictors. These bio-behavioral measures, including the K/T and P/T ratios, were also examined as predictors of greater risk for depression over 15 months. RESULTS: Higher time-varying sCD14 levels (ß = 0.13; P = 0.04) and time-varying detectable viral loads (ß = 0.71; P < 0.001) were independent predictors of a higher K/T ratio. Time-varying reactive urine toxicology results for stimulants (ß = 0.53; P < 0.001) and greater proviral HIV DNA at baseline (ß = 0.34; P < 0.001) independently predicted an increased P/T ratio. Greater time-varying, self-reported methamphetamine use uniquely predicted higher odds of screening positive for depression (Adjusted Odds Ratio = 1.08; 95% confidence interval: 1.01 to 1.17). CONCLUSIONS: Ongoing stimulant use and HIV persistence independently predict dysregulated metabolism of amino acid precursors for catecholamines, but this did not explain amplified risk for depression.

Tryptophan degradation is associated with risk-taking propensity in methamphetamine users with treated HIV infection.

Few studies have examined neuroimmune pathways that could contribute to impulsivity in people living with HIV who use substances. Eighty-four methamphetamine-using, sexual minority men with an undetectable HIV viral load were administered the Balloon Analogue Risk Task (BART), a behavioral measure of risk-taking propensity. We examined the associations between kynurenine/tryptophan ratio and phenylalanine/tyrosine ratio with BART scores using multiple linear regression. A higher kynurenine/tryptophan ratio was independently associated with greater BART scores (beta = 0.25; 95% CI = 0.05-1.23; p = 0.034). The phenylalanine/tyrosine ratio was not significantly associated with BART scores. Findings support the need for further research to elucidate the neuroimmune mechanisms linking tryptophan degradation with impulsivity to catalyze the development novel pharmacologic treatments for people living with HIV who use methamphetamine.

Getting to the point: Methamphetamine injection is associated with biomarkers relevant to HIV pathogenesis.

BACKGROUND: People living with HIV who use stimulants, such as methamphetamine, display greater immune dysregulation and experience faster clinical HIV progression. However, it remains unclear if the extent of immune dysregulation differs between methamphetamine users who engage in injection drug use (Meth IDU) and methamphetamine users who do not. METHODS: This cross-sectional study enrolled 86 sexual minority men living with HIV who had an undetectable viral load (< 40 copies/mL) and recent, biologically confirmed methamphetamine use. Meth IDU participants were compared to methamphetamine users who did not report IDU with respect to microbial translocation, immune activation, and inflammation plasma biomarkers. Multiple linear regression models were adjusted for age, antiretroviral therapy regimen, CD4 + T-cell count, and reactive urine toxicology results (Tox+) for stimulants. RESULTS: The Meth IDU participants were significantly more likely to be homeless and Tox + for stimulants. In adjusted analyses, those reporting Meth IDU displayed elevated plasma levels of lipopolysaccharide binding protein (LBP), soluble CD163 (sCD163), interleukin-6 (IL-6), and soluble tumor necrosis factor - alpha receptor I (sTNF-αRI). DISCUSSION: Even among methamphetamine users with treated HIV, those who engage in Meth IDU display exacerbations in key pathophysiologic processes that are linked to faster clinical HIV progression. These findings highlight the importance of screening for Meth IDU, discussing safer injection practices, and providing linkages to needle exchanges to reduce the harms of Meth IDU. Those who are not ready, willing, or able to abstain from methamphetamine use could also derive important health benefits from avoiding Meth IDU.

Identifying factors associated with successful implementation and uptake of an evidence-based voluntary medical male circumcision program in Zambia: the Spear and Shield 2 Program.

Voluntary medical male circumcision has been shown to provide a 50%-70% reduction in the risk of HIV infection without contributing to behavioral disinhibition of safer sexual practices. This study examined the interim implementation and dissemination data of Spear and Shield 2, an HIV risk-reduction program in Zambia. The purpose of this interim review was to identify contextual challenges to implementation and implement midcourse corrections associated with sustainability of program delivery. Using a mixed-methods design, quantitative evaluations of organizational functioning, barriers to implementation, burnout, and organizational readiness, as well as qualitative data utilizing the Consolidated Framework for Implementation Research (CFIR), were examined to evaluate program implementation. Participants were 184 health care providers from 46 clinics in Zambia. Successful implementation was associated with better community and leader support, and employee readiness and motivation. Quantitative assessments were not related to implementation and provided a limited picture of implementation outcomes. Results suggest that the qualitative data underlying the CFIR constructs provided a nuanced, contextual assessment of implementation, and dissemination outcomes. The CFIR may be valuable in informing the implementation of evidence-based interventions in other parts of Zambia.

Reproductive decision-making among postpartum HIV-infected women in rural South Africa.

Despite pregnancy spacing recommendations to optimize health outcomes among mothers and neonates, unplanned pregnancy in sub-Saharan Africa is common among women living with human immunodeficiency virus (HIV) (WLHIV). This study examined factors associated with reproductive decision-making among WLHIV to inform pregnancy-planning interventions. WLHIV in rural South Africa (n = 165) were assessed at 12 months postpartum. The relative importance of factors associated with reproductive decision-making was estimated. Women were a mean of 28 years old (SD = 5.71). Risk of mother-to-child transmission (MTCT) of HIV (Mean = 0.43; SD = 0.33) had the greatest impact on decision-making, followed by partners' desires (M = 0.22; SD = 0.18), family preferences (M = 0.18; SD = 0.13), and community opinion (M = 0.17; SD = 0.13). MTCT was most important to women with greater HIV knowledge. However, WLHIV who had been diagnosed with HIV for a longer time placed more emphasis on partner preference and community opinion, and less importance on MTCT risk. Prevention of mother-to-child transmission (PMTCT) was less important to women experiencing intimate partner violence and those with depression. Findings highlight the need for tailored, focused interventions to support the unique circumstances of WLHIV and support the inclusion of families and/or partners in the counseling process. Results underscore the need for perinatal preconception counseling for women during routine HIV care.