The Role of Behavioral and Neurocognitive Functioning in Substance Use Among Youth with Perinatally Acquired HIV Infection and Perinatal HIV Exposure Without Infection.

This study examined associations of self-regulatory behavior and cognitive functioning with substance use (SU) to inform interventions for youth with perinatal HIV infection (YPHIV) or exposure but uninfected (YPHEU). Youth aged 7-15 years (YPHIV, n = 390; YPHEU, n = 211) were followed longitudinally with cognitive testing and behavioral questionnaires including self-report of alcohol, marijuana, tobacco, and other SU. Cox proportional hazards analyses were used to examine correlates of initiating each substance for those without prior use at baseline and generalized estimating equation analyses were used to address associations of cognitive/behavioral measurements with SU prevalence for the entire sample. Lower self-reported self-regulation skills, but higher cognitive functioning abilities, were associated with initiation and prevalent use of alcohol and marijuana regardless of HIV status. Our findings suggest SU screening tools and self-regulation interventions developed for general adolescent populations should be implemented for those with PHIV, who may be at heightened risk for SU-related health consequences.

RESUMEN: En este estudio se examina el vínculo del comportamiento autorregulado y la función cognoscitiva con el consumo de sustancias para argumentar intervenciones para los jóvenes con infección perinatal por el VIH (JIPVIH) y los jóvenes con exposición perinatal sin infección por el VIH (JEPSIVIH). Se hizo un seguimiento longitudinal de jóvenes de 7 a 15 años de edad (JIPVIH, n = 390; JEPSIVIH, n = 211) por medio de pruebas cognoscitivas y cuestionarios sobre el comportamiento, incluyendo el autoinforme de consumo de alcohol, marihuana, tabaco y otras sustancias. Se usaron los análisis Cox de riesgos proporcionales para examinar factores correlacionados con el inicio del consumo de cada sustancia por personas no consumidoras en el punto de referencia inicial. Asimismo, se usaron análisis de ecuaciones de estimación generalizadas para examinar la asociación entre la prevalencia del consumo de sustancias y las medidas cognoscitivas y las medidas conductuales para toda la muestra. Habilidades de autorregulación disminuidas, según autoinforme, pero capacidades superiores de función cognoscitiva, fueron vinculadas con el inicio y consumo frecuente de alcohol y marihuana, independientemente de la condición de VIH. Nuestros hallazgos sugieren que herramientas para detectar el consumo de sustancias e intervenciones de autorregulación creadas para la población general de adolescentes se deberían implementar para los JIPVIH que podrían correr mayores riesgos de sufrir consecuencias en la salud relacionadas con el consumo de sustancias.

Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV.

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load.

Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV.

Ferroptosis is implicated in viral neuropathogenesis and may underlie HIV-associated neurocognitive impairment (NCI). Emerging data also suggest differences in brain iron transport by sex. We hypothesized that circulating ferritins that inhibit ferroptosis associate with neurocognitive function and NCI in people with HIV (PWH) in a sex-biased manner. Serum ferritin heavy-chain-1 (FTH1), ferritin light-chain (FTL), and urinary F2-isoprostanes (uF2-isoPs, specific lipid peroxidation marker) were quantified in 324 PWH (including 61 women) with serial global (NPZ-4) and domain-specific neurocognitive testing. Biomarker associations with neurocognitive test scores and NCIs were evaluated by multivariable regression; correlations with uF2-isoPs were also assessed. Higher FTL and FTH1 levels were associated with less NCI in all PWH (adjusted odds ratios 0.53, 95% confidence interval (95% CI) 0.36-0.79 and 0.66, 95% CI 0.45-0.97, respectively). In women, higher FTL and FTH1 were also associated with better NPZ-4 (FTL adjusted beta (ß) = 0.15, 95% CI 0.02-0.29; FTL-by-sex ßinteraction = 0.32, p = 0.047) and domain-specific neurocognitive test scores. Effects on neurocognitive performance persisted for up to 5 years. Levels of both ferritins correlated inversely with uF2-isoPs in women (FTL: rho = -0.47, p < 0.001). Circulating FTL and FTH1 exert sustained, sex-biased neuroprotective effects in PWH, possibly by protecting against iron-mediated lipid peroxidation (ferroptosis). Larger studies are needed to confirm the observed sex differences and further delineate the underlying mechanisms.

Regional Differences in Risk of Recurrent Falls Among Older U.S. Women and Men with HIV in the HIV Infection, Aging, and Immune Function Long-Term Observational Study.

Geographic location was a strong predictor of falls among women with and without HIV in the Women's Interagency HIV Study. We examined regional variation in falls in a more geographically diverse cohort of older people with HIV (PWH) and explored whether physical activity, sex, or body-mass index modified these associations. PWH enrolled in the A5322 HAILO (HIV Infection, Aging, and Immune Function Long-Term Observational Study). Participants who reported falls in the 6 months before each semiannual visit and had ≥1 consecutive pair of fall assessments were included. We examined associations of geographic region [Northeast, Midwest, South, and West] with recurrent falls (≥2) over each 12-month period using repeated measures multinomial logistic regression models and assessed effect modification by adding an interaction term between geographic region and each potential effect modifier. A total of 788 men and 192 women with median age of 51 years at study entry contributed up to 240 weeks of data. U.S. regions included Northeast (22%), Midwest (29%), South (20%), and West (28%). In multivariable analyses, compared with the Western region, greater risk was seen among Midwestern (odds ratio [OR] = 2.35 [95% confidence interval (CI) = 1.29-4.28]) and Southern regions (OR = 2.09 [95% CI = 1.09-4.01]). Among those with higher physical activity, the Midwestern region had higher odds of recurrent falls than the Western region. Among obese individuals, the Southern region had higher odds of recurrent falls than the Western region. Sex did not modify the association between region and recurrent falls. Among older PWH, fall risk varied by geographic region. Associations between geographic region and recurrent falls appeared to be modified by physical activity and obesity. This may help identify subgroups of older PWH for targeted fall screening/interventions.

Effect of Clonal Hematopoiesis on Cardiovascular Disease in People Living with HIV.

Hematopoietic stem cells (HSCs) with age-associated somatic mutations that disproportionally contribute to hematopoiesis generate the condition known as clonal hematopoiesis (CH). While CH conveys increased risk of hematologic cancer, there is also strong association between CH and cardiovascular disease (CVD). Accumulating evidence suggests that inflammation mechanistically links CH to CVD, and we hypothesized that CH may be a predictive biomarker of CVD in conditions of chronic inflammation. One such patient population comprises people living with HIV (PLWH) who also have substantially increased incidences of CVD and CH . We studied the association between CH and CVD in PLWH using samples from ACTG Study A5001 (or ALLRT), a prospective clinical trial of HIV-infected persons with long-term follow-up. We observed a positive association between CH and CVD in PLWH independent of traditional CVD risk factors. Moreover, in CVD cases, the CH clone was identifiable in the blood years before CVD diagnosis, unlike in PLWH with CH who did not have CVD. With the life span of PLWH increasing because of advances in treatment, our results indicate that the presence of CH and its clonal dynamics could be used as a prognostic biomarker of the risk for CVD in PLWH.

Predictors of herpes simplex virus type 2 prevalence and incidence among bar and hotel workers in Moshi, Tanzania.

BACKGROUND: Herpes simplex virus (HSV) type 2 increases the risk of human immunodeficiency virus (HIV) infection, and, in regions with high prevalence of both viruses, control of HSV-2 may be an effective method of HIV prevention. Identification of modifiable factors for prevention of HSV-2 infection is essential. We conducted this study among female bar and hotel workers in Moshi, Tanzania. METHODS: Factors associated with prevalent infection were examined among 1039 women. Predictors of incident infection were examined among 360 women initially HSV-2 negative, with at least 1 follow-up visit. RESULTS: HSV-2 prevalence was 56.3% (95% confidence interval [CI], 53.3%-59.3%). Only 2.5% of women able to name a sexually transmitted infection named herpes. Incidence was 14.2 cases/100 person-years (95% CI, 10.5-18.8 cases/100 person-years). Incident HSV-2 infection was independently associated with HIV infection, younger age of sexual initiation, ethnicity, alcohol consumption, and having a male partner with other sexual partners. CONCLUSIONS: The occurrence of HSV-2 is high in this population, but knowledge is low. Development of education programs to increase awareness of HSV-2 is critical. The control of both HSV-2 and HIV infections is a major public health priority in Moshi. Prevention interventions in this and other high prevalence populations might most effectively target younger women, before initiation of sexual activity.

Sexual behavior, psychosocial and knowledge differences between consistent, inconsistent and non-users of condoms: a study of female bar and hotel workers in Moshi, Tanzania.

Understanding psychosocial, sexual behavior and knowledge differences between never, inconsistent and consistent condom users can improve interventions to increase condom use in resource-poor countries, but they have not been adequately studied. We examined these differences in a cohort of 961 female hotel and bar workers in Moshi, Tanzania. Forty-nine percent of women reported no condom use; 39% reported inconsistent use, and 12% reported consistent use. Women with multiple sexual partners in the past five years were less likely to be consistent rather than inconsistent users as were women who had ever exchanged sex for gifts or money. Inconsistent users had higher condom knowledge and higher perceived acceptability of condom use than did never users, but they did not differ from consistent users by these factors. There are important differences between women by level of condom use. These findings can help inform interventions to increase condom use.