Brief Report: Substance Use Care Continuum in Women With and Without HIV in the Southern United States.

BACKGROUND: Substance use (SU) contributes to poor outcomes among persons living with HIV. Women living with HIV (WWH) in the United States are disproportionately affected in the South, and examining SU patterns, treatment, and HIV outcomes in this population is integral to addressing HIV and SU disparities. METHODS: WWH and comparable women without HIV (WWOH) who enrolled 2013-2015 in the Women's Interagency HIV Study Southern sites (Atlanta, Birmingham/Jackson, Chapel Hill, and Miami) and reported SU (self-reported nonmedical use of drugs) in the past year were included. SU and treatment were described annually from enrollment to the end of follow-up. HIV outcomes were compared by SU treatment engagement. RESULTS: At enrollment, among 840 women (608 WWH, 232 WWOH), 18% (n = 155) reported SU in the past year (16% WWH, 24% WWOH); 25% (n = 38) of whom reported SU treatment. Over time, 30%, 21%, and 18% reported SU treatment at 1, 2, and 3 years, respectively, which did not significantly differ by HIV status. Retention in HIV care did not differ by SU treatment. Viral suppression was significantly higher in women who reported SU treatment only at enrollment ( P = 0.03). CONCLUSIONS: We identified a substantial gap in SU treatment engagement, with only a quarter reporting treatment utilization, which persisted over time. SU treatment engagement was associated with viral suppression at enrollment but not at other time points or with retention in HIV care. These findings can identify gaps and guide future strategies for integrating HIV and SU care for WWH.

Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.

Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum ß-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.

Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019.

Importance: Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV. Objective: To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era. Design, Setting, and Participants: This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021. Exposures: HIV, age, sex. Main Outcomes and Measures: Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden. Results: A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance. Conclusions and Relevance: In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

Obesity Modifies the Relationship Between Raltegravir and Dolutegravir Hair Concentrations and Body Weight Gain in Women Living with HIV.

Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in women living with HIV (WLH). Relationships between drug exposure, baseline obesity, and INSTI-associated weight gain remain unclear. Data from 2006 to 2016 were analyzed from virally suppressed WLH enrolled in the Women's Interagency HIV Study, who switched/added an INSTI to antiretroviral therapy: [raltegravir (RAL), dolutegravir (DTG), or elvitegravir (EVG)]. Percent body weight change was calculated from weights obtained a median 6 months pre-INSTI and 14 months post-INSTI initiation. Hair concentrations were measured with validated liquid chromatography-mass spectrometry (MS)/MS assays. Baseline (preswitch) weight status evaluated obese (body mass index, BMI, ≥30 kg/m2) versus nonobese (BMI <30 kg/m2). Mixed models examined the drug hair concentration*baseline obesity status interaction for each INSTI. There were 169 WLH included: 53 (31%) switched to RAL, 72 (43%) to DTG, and 44 (26%) to EVG. Women were median age 47-52 years, predominantly Non-Hispanic Black, median CD4 counts >500 cells/mm3, >75% with undetectable HIV-1 RNA. Over ∼1 year, women experienced median increases in body weight: 1.71% (-1.78, 5.00) with RAL; 2.40% (-2.82, 6.50) with EVG; and 2.48% (-3.60, 7.88) with DTG. Baseline obesity status modified the relationship between hair concentrations and percent weight change for DTG and RAL (p's < 0.05): higher DTG, yet lower RAL concentrations were associated with greater weight gain among nonobese women. Additional pharmacologic assessments are needed to understand the role of drug exposure in INSTI-associated weight gain.

Feasibility of an Open Dialogue-Inspired Approach for Young Adults with Psychosis in a Public Hospital System.

The objective was to determine the feasibility of an Open Dialogue-inspired approach in a metropolitan, public hospital setting with predominately African American participants. Participants were ages 18-35, experienced psychosis within the past month, and involved at least one support person in their care. We evaluated domains of feasibility including implementation, adaptation, practicality, acceptability, and limited-efficacy. An organizational change model (Addressing Problems Through Organizational Change) facilitated implementation. Clinicians received three trainings and ongoing supervision. Network meetings were successfully implemented with good self-reported fidelity to principles of dialogic practice. Some adaptations (less frequent meetings and no home visits) were necessary. A subset of individuals completed research assessments over 12 months. Qualitative interviews with participants suggested the intervention was acceptable. Symptom and functional outcomes were preliminary but trended toward improvement. Implementation was feasible with relatively brief training, organizational change processes, and context-specific adaptations. Lessons learned can assist in planning a larger research study.

Substance Use Treatment Utilization Among Women With and Without Human Immunodeficiency Virus.

Background: Substance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS). Methods: We included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations between participant characteristics and SU treatment. Results: Among 2559 women (1802 women living with HIV [WWH], 757 women without HIV), 14% reported current SU. Among those with current SU (n = 367), 71% reported crack/cocaine followed by 40% reporting opioids, and 42% reported any treatment in the past year. The most common treatments were methadone (64%), Narcotics Anonymous (29%), inpatient programs (28%), and outpatient programs (16%). Among women using opioids (n = 147), 67% reported methadone use in the past year compared to 5% using buprenorphine/naloxone. Multivariable analysis showed lower odds of treatment utilization among WWH with concurrent alcohol or marijuana use. Visiting a psychiatrist/counselor was associated with higher odds of treatment. Among WWH, SU treatment was not associated with HIV-related clinical outcomes. Conclusions: Treatment utilization was high, especially for methadone use. Our results highlight opportunities for accessing SU treatment for WWH, such as the need to prioritize buprenorphine and comprehensive, wraparound services in HIV care settings.

The Effect of Menopausal Status, Age, and Human Immunodeficiency Virus (HIV) on Non-AIDS Comorbidity Burden Among US Women.

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without human immunodeficiency virus (HIV). We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden, and that HIV impacted burden most in the pre-/perimenopausal phases.

Evaluating the impact of three progestin-based hormonal contraceptive methods on immunologic changes in the female genital tract and systemically (CHIME Study): a prospective cohort study protocol.

BACKGROUND: Gonadal hormones can modify immune function, which may impact susceptibility to infectious diseases, including Human Immunodeficiency Virus (HIV). There is limited knowledge about how hormonal contraceptives (HC) influence the immune response during the course of use. The CHIME study aims to evaluate the effect of long-acting progestin-based hormonal contraceptives (depot medroxyprogesterone acetate, etonogestrel implant, and levonorgestrel intrauterine device) on immunologic changes in the female genital tract (FGT) and systemic compartment. METHODS: CHIME is an observational cohort study where participants attend 2 visits prior to initiating the HC method of their choice, and then attend 6 visits over 12 months with biological sampling (vaginal swabs, cervicovaginal lavage, cytobrush and blood) for immunological, bacteriological, and virological analyses at each visit. Immune profiling will be evaluated by multi-color flow cytometry to determine how different T-cell subsets, in particular the CD4 T-cell subsets, change during the course of contraceptive use and whether they have different profiles in the FGT compared to the systemic compartment. The study aims are (1) to characterize the alterations in FGT and systemic immune profiles associated with three long-acting progestin-only HC and (2) to evaluate the vaginal microenvironment, determined by 16 s rRNA sequencing, as an individual-level risk factor and moderator of genital and systemic immune profile changes following exposure to three commonly used HC. Data collection started in March 2019 and is scheduled to be completed in October 2024. DISCUSSION: The CHIME study aims to contribute to the body of research designed to evaluate the comparative impact of three long-acting progestin-only HC on innate and adaptive immune functions to understand how immunologic effects alter STI and HIV susceptibility.

Bone, Brain, Heart study protocol: A resilient nested, tripartite prospective cohort study of the role of estrogen depletion on HIV pathology.

PURPOSE: We describe the rationale for and design of an innovative, nested, tripartite prospective observational cohort study examining whether relative estrogen insufficiency-induced inflammation amplifies HIV-induced inflammation to cause end organ damage and worsen age-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (Brain), skeletal (Bone), and cardiovascular (Heart/vessels) organ systems (BBH Study). METHODS: The BBH parent study is the Multicenter AIDS Cohort/Women's Interagency HIV Study Combined Cohort Study (MWCCS) with participants drawn from the Atlanta MWCCS site. BBH will enroll a single cohort of n = 120 women living with HIV and n = 60 HIV-negative women, equally distributed by menopausal status. The innovative multipart nested study design of BBH, which draws on data collected by the parent study, efficiently leverages resources for maximum research impact and requires extensive oversight and management in addition to careful implementation. The presence of strong infrastructure minimized BBH study disruptions due to changes in the parent study and the COVID-19 pandemic. CONCLUSION: BBH is poised to provide insight into sex and HIV associations with the neuro-hypothalamic-pituitary-adrenal axis, skeletal, and cardiovascular systems despite several major, unexpected challenges.

Glucocorticoid Receptor Function and Cognitive Performance in Women With HIV.

OBJECTIVE: Alterations in glucocorticoid receptor (GCR) function may be a risk factor for cognitive complications among older people with human immunodeficiency virus (HIV). We evaluated whether HIV serostatus and age modify the GCR function-cognition association among women. METHODS: Eighty women with HIV ( n = 40, <40 years of age [younger]; n = 40, >50 years of age [older]) and 80 HIV-uninfected women ( n = 40 older, n = 40 younger) enrolled in the Women's Interagency HIV Study completed a comprehensive neuropsychological test battery. Peripheral blood mononuclear cells collected concurrent with neuropsychological testing were assessed for GCR function. Multivariable linear regression analyses were conducted to examine whether a) HIV serostatus and age were associated with GCR function, and b) GCR function-cognition associations are moderated by HIV serostatus and age adjusting for relevant covariates. RESULTS: Among older women, higher baseline FKBP5 expression level was associated with lower attention/working memory performance among women with HIV ( B = 6.4, standard error = 1.7, p = .0003) but not in women without HIV infection ( B = -1.7, standard error = 1.9, p = .37). There were no significant HIV serostatus by age interactions on dexamethasone (DEX)-stimulated expression of the genes regulated by the GCR or lipopolysaccharide-stimulated tumor necrosis factor α levels (with or without DEX stimulation; p values > .13). HIV serostatus was associated with GC target genes PER1 ( p = .006) and DUSP1 ( p = .02), but not TSC22D3 ( p = .32), after DEX stimulation. CONCLUSIONS: Collectively, these data suggest that HIV serostatus and age may modify the influence of the GCR, such that the receptor is likely engaged to a similar extent, but the downstream influence of the receptor is altered, potentially through epigenetic modification of target genes.

Nested and multipart prospective observational studies, flaming fiasco or efficiently economical?: The Brain, Bone, Heart case study.

BACKGROUND: Collecting new data from cross-sectional/survey and cohort observational study designs can be expensive and time-consuming. Nested (hierarchically cocooned within an existing parent study) and/or Multipart (≥ 2 integrally interlinked projects) study designs can expand the scope of a prospective observational research program beyond what might otherwise be possible with available funding and personnel. The Brain, Bone, Heart (BBH) study provides an exemplary case to describe the real-world advantages, challenges, considerations, and insights from these complex designs. MAIN: BBH is a Nested, Multipart study conducted by the Specialized Center for Research Excellence (SCORE) on Sex Differences at Emory University. BBH is designed to examine whether estrogen insufficiency-induced inflammation compounds HIV-induced inflammation, leading to end-organ damage and aging-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (brain), musculoskeletal (bone), and cardiovascular (heart) organ systems. Using BBH as a real-world case study, we describe the advantages and challenges of Nested and Multipart prospective cohort study design in practice. While excessive dependence on its parent study can pose challenges in a Nested study, there are significant advantages to the study design as well. These include the ability to leverage a parent study's resources and personnel; more comprehensive data collection and data sharing options; a broadened community of researchers for collaboration; dedicated longitudinal research participants; and, access to historical data. Multipart, interlinked studies that share a common cohort of participants and pool of resources have the advantage of dedicated key personnel and the challenge of increased organizational complexity. Important considerations for each study design include the stability and administration of the parent study (Nested) and the cohesiveness of linkage elements and staff organizational capacity (Multipart). CONCLUSION: Using the experience of BBH as an example, Nested and/or Multipart study designs have both distinct advantages and potential vulnerabilities that warrant consideration and require strong biostatistics and data management leadership to optimize programmatic success and impact.

Follow-Up to High-Resolution Anoscopy After Abnormal Anal Cytology in People Living with HIV.

Current expert recommendations suggest anal cytology followed by high-resolution anoscopy (HRA) for biopsy and histological confirmation may be beneficial in cancer prevention, especially in people living with HIV (PLWH). Guided by the social ecological model, the purpose of this study was to examine sociodemographic and clinical variables, individual-level factors (depression, HIV/AIDS-related stigma, and health beliefs) and interpersonal-level factors (social support) related to time to HRA follow-up after abnormal anal cytology. We enrolled 150 PLWH from a large HIV community clinic, with on-site HRA availability, in Atlanta, GA. The median age was 46 years (interquartile range of 37-52), 78.5% identified as African American/Black, and 88.6% identified as born male. The average length of follow-up to HRA after abnormal anal cytology was 380.6 days (standard deviation = 317.23). Only 24.3% (n = 39) of the sample had an HRA within 6 months after an abnormal anal cytology, whereas 57% of the sample had an HRA within 12 months. HIV/AIDS-related stigma [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.33-0.90] and health motivation (OR 0.80, 95% CI 0.67-0.95) were associated with time to HRA follow-up ≤6 months. For HRA follow-up ≤12 months, we found anal cytology [high-grade squamous intraepithelial lesions/atypical squamous cells of undetermined significance cannot exclude HSIL (HSIL/ASCUS-H) vs. low-grade squamous intraepithelial lesions (LSIL) OR = 0.05, 95% CI 0.00-0.70; atypical squamous cells of undetermined significance (ASCUS) vs. LSIL OR = 0.12, 95% CI 0.02-0.64] and health motivation (OR = 0.86, 95% CI 0.65-0.99) were associated. Findings from this study can inform strategies to improve follow-up care after abnormal anal cytology at an individual and interpersonal level in efforts to decrease anal cancer morbidity and mortality.

Cognitively Based Compassion Training for HIV Immune Nonresponders-An Attention-Placebo Randomized Controlled Trial.

OBJECTIVE: Chronic inflammation is associated with increased morbidity and mortality for people with HIV (PWH). Psychological stress is an important contributor to this chronic inflammation. We hypothesized that a cognitively based compassion training (CBCT) approach could reduce inflammation and psychological stress in immune nonresponder PWH. DESIGN: An attention-placebo randomized controlled trial design to evaluate the acceptability of CBCT among PWH and its effects on key aspects of stress and immune function compared with an active-attention control group (NCT02395289). METHODS: This study was conducted at an HIV clinic in Atlanta, Georgia. Eligible individuals determined by (1) adherence to antiretroviral therapy for at least a year, (2) virologic suppression; and (3) stable CD4+ T-cell counts <350 cells/µL were randomized in a 2:1 ratio to either CBCT or control in 2 study periods: April-May, 2016, and September-December, 2016. Psychological measures and inflammatory biomarkers associated with HIV disease progression (IL-1ß, TNF-α, sCD14, IL-6, and IL-10) were obtained for all study participants at baseline and at the time of study completion. RESULTS: We found a significant association between CBCT practice time engagement and fold reduction in IL-6 and TNF-α levels. There was no association between CBCT practice time and other biomarkers markers assessed (IL-1ß, sCD14, and IL-10). These changes were coincident with significant increases in self-reported psychological well-being and HIV disease acceptance and in benefits for CBCT participants. We also observed fewer instances of virologic failure for those in the CBCT arm compared with controls. CONCLUSIONS: CBCT is a novel and feasible nonmedication-based intervention that could reduce inflammation and psychological stress in PWH.

Psychosocial Mechanisms of Self-rated Successful Aging with HIV: A Structural Equation Model.

This study tested a conceptual psychosocial model of self-rated successful aging (SRSA) with HIV. Our sample (n = 356) included older women living with HIV (OWLH): average age 56.5 years, 73% Black. SRSA was assessed using a research-based 10-point scale (higher scores = better outcomes). We conducted adjusted structural equation modeling. The global model included two latent variables-protective attributes (composite of positive psychosocial factors: resilience, personal mastery, optimism, spirituality) and psychological distress (composite of negative psychosocial factors: anxiety, depression, loneliness, internalized HIV-related stigma). The model showed good fit (χ2(58) = 76, p = 0.06; RMSEA = 0.03; CFI = 0.99). Increased protective attributes were associated with improved SRSA both directly and mediated by improved coping with stress. While psychological distress did not have a direct effect on SRSA, it was indirectly associated with worsened SRSA via diminished protective attributes and via decreased coping with stress. Findings suggest the need for interventions enhancing positive and mitigating negative psychosocial factors in OWLH.

Incident Non-AIDS Comorbidity Burden Among Women With or at Risk for Human Immunodeficiency Virus in the United States.

BACKGROUND: Human immunodeficiency virus (HIV) infection may accelerate development of aging-related non-AIDS comorbidities (NACMs). The incidence of NACMs is poorly characterized among women living with HIV (WLWH). METHODS: WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through 2009 (when >80% of WLWH used antiretroviral therapy) or onward were included, with outcomes measured through 31 March 2018. Sociodemographics, clinical covariates, and prevalent NACM were determined at enrollment. We used Poisson regression models to determine incident NACM burden (number of NACMs accrued through most recent WIHS visit out of 10 total NACMs assessed) by HIV serostatus and age. RESULTS: There were 3129 participants (2239 WLWH, 890 HIV seronegative) with 36 589 person-years of follow-up. At enrollment, median age was 37 years, 65% were black, and 47% currently smoked. In fully adjusted analyses, WLWH had a higher incident NACM rate compared with HIV-seronegative women (incidence rate ratio, 1.36 [95% confidence interval (CI), 1.02-1.81]). Incident NACM burden was higher among WLWH vs HIV-seronegative women in most age strata (HIV × age interaction: P = .0438), and women <25 years old had the greatest incidence rate ratio by HIV serostatus at 1.48 (95% CI, 1.19-1.84) compared with those in older age groups. Incident NACM burden was associated with traditional comorbidity risk factors but not HIV-specific indices. CONCLUSIONS: Incident NACM burden was higher among WLWH than HIV-seronegative women. This difference was most dramatic among women aged <25 years, a group for whom routine comorbidity screening is not prioritized. Established non-HIV comorbidity risk factors were significantly associated with incident NACM burden. More data are needed to inform best practices for NACM screening, prevention, and management among WLWH, particularly young women.

The Prevalence and Burden of Non-AIDS Comorbidities Among Women Living With or at Risk for Human Immunodeficiency Virus Infection in the United States.

BACKGROUND: The prevalence and burden of age-related non-AIDS comorbidities (NACMs) are poorly characterized among women living with HIV (WLWH). METHODS: Virologically suppressed WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through at least 2009 (when >80% of WLWH used antiretroviral therapy) were included, with outcomes measured through 31 March 2018. Covariates, NACM number, and prevalence were summarized at most recent WIHS visit. We used linear regression models to determine NACM burden by HIV serostatus and age. RESULTS: Among 3232 women (2309 WLWH, 923 HIV-seronegative) with median observation of 15.3 years, median age and body mass index (BMI) were 50 years and 30 kg/m2, respectively; 65% were black; 70% ever used cigarettes. WLWH had a higher mean NACM number than HIV-seronegative women (3.6 vs 3.0, P < .0001) and higher prevalence of psychiatric illness, dyslipidemia, non-AIDS cancer, kidney, liver, and bone disease (all P < .01). Prevalent hypertension, diabetes, and cardiovascular and lung disease did not differ by HIV serostatus. Estimated NACM burden was higher among WLWH versus HIV-seronegative women in those aged 40-49 (P < .0001) and ≥60 years (P = .0009) (HIV × age interaction, P = .0978). In adjusted analyses, NACM burden was associated with HIV, age, race, income, BMI, alcohol abstinence, cigarette, and crack/cocaine use; in WLWH, additional HIV-specific indices were not associated, aside from recent abacavir use. CONCLUSIONS: Overall, NACM burden was high in the cohort, but higher in WLWH and in certain age groups. Non-HIV traditional risk factors were significantly associated with NACM burden in WLWH and should be prioritized in clinical guidelines for screening and intervention to mitigate comorbidity burden in this high-risk population.

Contraception methods used among women with HIV starting antiretroviral therapy in a large United States clinical trial, 2009-2011.

OBJECTIVE(S): We describe contraception and dual method use among women with HIV initiating antiretroviral therapy (ART) in a U.S. clinical trial and examine associated factors. STUDY DESIGN: We analyzed data from ART-naïve women aged 45 years and under initiating one of 3 regimens as part of A5257 (May 2009-June 2011) which required that women at risk for pregnancy use contraception. We classified self-reported methods as more effective (Tier 1 [intrauterine device, hysterectomy, permanent contraception] and Tier 2 [hormonal rings, patches, injections, pills]) versus less effective (Tier 3 [condoms alone] and Tier 4 [withdrawal, none]). We used logistic regression models to assess associations with use of (a) more effective, and (b) dual methods (condoms with a more effective method). RESULTS: Of 285 women, majority were Black (59%), had annual income <$20,000 (54%), and had government insurance (68%). The most common contraceptive methods reported at baseline were permanent contraception (37%), male condoms alone (31%), and injectable progestin (8%); 41% and 16% reported Tier 1 and 2 use, respectively; 36% reported dual method use. Use of more effective and dual methods did not change 48 and 96 weeks after ART initiation (p > 0.05). In multivariable analyses, baseline use of more effective and dual methods was associated with age at least 40 years versus 18 to 29 years (odds ratio [OR] 4.46, 95% confidence interval [CI] 2.12, 9.35) and having at least one child (OR 2.31, 95%CI 1.27, 4.20). CONCLUSIONS: In women initiating modern ART in a clinical trial, permanent contraception was common, while use of other more effective contraceptive methods was low and did not change after ART initiation. Efforts are needed to improve integration of family planning services for women within the context of HIV clinical trials. IMPLICATIONS: The findings highlight the importance of improving integration of HIV and family planning services, including in the context of clinical trials.

Metabolic Changes Associated With the Use of Integrase Strand Transfer Inhibitors Among Virally Controlled Women.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) have been associated with weight gain among women living with HIV. We aimed to investigate the association between INSTIs and change in cardiometabolic risk indicators. SETTING: Retrospective cohort. METHODS: Data from 2006 to 2017 were analyzed from women living with HIV enrolled in the longitudinal Women's Interagency HIV Study who were virally controlled on antiretroviral therapy (ART) for ≥5 consecutive semiannual visits. Women who switched/added an INSTI to ART (INSTI group) were compared with women who remained on non-INSTI ART (non-INSTI group). Outcomes included changes in fasting lipids and glucose, hemoglobin A1c (HbA1c), blood pressure (BP), and incident diabetes, hypertension, and insulin resistance. Outcomes were measured 6-12 months before and 6-18 months after INSTI switch/add in the INSTI group with comparable visits in the non-INSTI group. Longitudinal linear regression models compared change over time in each outcome by the study group. RESULTS: One thousand one hundred eighteen participants (234 INSTI, 884 non-INSTI) were followed for a median 2.0 (Q1 1.9, Q3 2.0) years. Participants were median age 49 years, 61% Black, and 73% overweight or obese (body mass index ≥25 kg/m). Compared with non-INSTI, the INSTI group experienced greater increases in HbA1c (+0.05 vs. -0.06 mg/dL, P = 0.0318), systolic BP (+3.84 vs. +0.84 mm Hg, P = 0.0191), and diastolic BP (+1.62 vs. -0.14 mm Hg, P = 0.0121), with greatest change in HbA1c among women on INSTIs with ≥5% weight gain. CONCLUSIONS: INSTI use was associated with unfavorable changes in HbA1c and systolic and diastolic BP during short-term follow-up. Further research is needed to understand long-term cardiometabolic effects of INSTI use.

Policy- and county-level associations with HIV pre-exposure prophylaxis use, the United States, 2018.

PURPOSE: HIV pre-exposure prophylaxis (PrEP) is highly efficacious, and yet most individuals indicated for it are not currently using it. To provide guidance for health policymakers, researchers, and community advocates, we developed county-level PrEP use estimates and assessed locality and policy associations. METHODS: Using data from a national aggregator, we applied a validated crosswalk procedure to generate county-level estimates of PrEP users in 2018. A multilevel Poisson regression explored associations between PrEP use and (1) state policy variables of Medicaid expansion and state Drug Assistance Programs (PrEP-DAPs) and (2) county-level characteristics from the U.S. Census Bureau. Outcomes were PrEP per population (prevalence) and PrEP-to-need ratio (PnR), defined as the ratio of PrEP users per new HIV diagnosis. Higher levels of PrEP prevalence or PnR indicate more PrEP users relative to the total population or estimated need, respectively. RESULTS: Our 2018 county-level data set included a total of 188,546 PrEP users in the United States. Nationally, PrEP prevalence was 70.3/100,000 population and PnR was 4.9. In an adjusted model, counties with a 5% higher proportion of black residents had 5% lower PnR (rate ratio (RR): 0.95, 95% confidence interval (CI): 0.93, 0.96). Similarly, counties with higher concentration of residents uninsured or living in poverty had lower PnR. Relative to states without Medicaid expansion or PrEP-DAPs, states with only one of those programs had 25% higher PrEP prevalence (RR: 1.25, 95% CI: 1.09, 1.45), and states with both programs had 99% higher PrEP prevalence (RR: 1.99, 95% CI: 1.60, 2.48). There was a significant linear trend across the three policy groups, and similar findings for the relation between PnR and the policy groups. CONCLUSIONS: In a data set comprising approximately 80% of PrEP users in the United States, we found that Medicaid expansion and PrEP-DAPs were associated with higher PrEP use in states that adopted those policies, after controlling for potential confounders. Future research should identify which components of PrEP support programs have the most success and how to best promote PrEP among groups most impacted by the epidemic. States should support the admirable health decisions of their residents to get on PrEP by implementing policies that facilitate access.

Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood.

BACKGROUND: While prior epidemiologic studies have suggested that injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) use may increase a woman's risk of acquiring HIV, recent data have suggested that DMPA users may be at a similar risk for HIV acquisition as users of the copper intrauterine device and levonorgestrel implant. Use of the etonogestrel Implant (Eng-Implant) is increasing but there are currently no studies evaluating its effect on HIV acquisition risk. OBJECTIVE: Evaluate the potential effect of the Eng-Implant use on HIV acquisition risk by analyzing HIV target cells and cytokine profiles in the lower genital tract and blood of adult premenopausal HIV-negative women using the Eng-Implant. METHODS: We prospectively obtained paired cervicovaginal lavage (CVL) and blood samples at 4 study visits over 16 weeks from women between ages 18-45, with normal menses (22-35 day intervals), HIV uninfected with no recent hormonal contraceptive or copper intrauterine device (IUD) use, no clinical signs of a sexually transmitted infection at enrollment and who were medically eligible to initiate Eng-Implant. Participants attended pre-Eng-Implant study visits (week -2, week 0) with the Eng-Implant inserted at the end of the week 0 study visit and returned for study visits at weeks 12 and 14. Genital tract leukocytes (enriched from CVL) and peripheral blood mononuclear cells (PBMC) from the study visits were evaluated for markers of activation (CD38, HLA-DR), retention (CD103) and trafficking (CCR7) on HIV target cells (CCR5+CD4+ T cells) using multicolor flow cytometry. Cytokines and chemokines in the CVL supernatant and blood plasma were measured in a Luminex assay. We estimated and compared study endpoints among the samples collected before and after contraception initiation with repeated-measures analyses using linear mixed models. RESULTS: Fifteen of 18 women who received an Eng-Implant completed all 4 study visits. The percentage of CD4+ T cells in CVL was not increased after implant placement but the percentage of CD4+ T cells expressing the HIV co-receptor CCR5 did increase after implant placement (p = 0.02). In addition, the percentage of central memory CD4+ T-cells (CCR7+) in CVL increased after implant placement (p = 0.004). The percentage of CVL CD4+, CCR5+ HIV target cells expressing activation markers after implant placement was either reduced (HLA-DR+, p = 0.01) or unchanged (CD38+, p = 0.45). Most CVL cytokine and chemokine concentrations were not significantly different after implant placement except for a higher level of the soluble lymphocyte activation marker (sCD40L; p = 0.04) and lower levels of IL12p70 (p = 0.02) and G-CSF (p<0.001). In systemic blood, none of the changes noted in CVL after implant placement occurred except for decreases in the percentage CD4 T-cells expressing HLA-DR+ T cells (p = 0.006) and G-CSF (p = 0.02). CONCLUSIONS: Eng-Implant use was associated with a moderate increase in the availability of HIV target cells in the genital tract, however the percentage of these cells that were activated did not increase and there were minimal shifts in the overall immune environment. Given the mixed nature of these findings, it is unclear if these implant-induced changes alter HIV risk.