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Background To evaluate the effect of cumulative human immunodeficiency virus (HIV)-1 viremia on aging-related multimorbidity among women with HIV (WWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997–2019). Methods We included WWH with ≥2 plasma HIV-1 viral loads (VL) <200 copies/mL within a 2-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 nonacquired immune deficiency syndrome comorbidities [NACM] of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (eg, age, CD4 count, etc). Results Eight hundred six WWH contributed 6368 women-years, with median 12 (Q1–Q3, 7–23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cells/mm3. Median time-updated cumulative VCY was 5.4 (Q1–Q3, 4.7–6.9) log10 copy-years/mL. Of 211 (26%) WWH who developed multimorbidity, 162 (77%) had incident hypertension, 133 (63%) had dyslipidemia, 60 (28%) had diabetes, 52 (25%) had cardiovascular disease, and 32 (15%) had kidney disease. Compared with WWH who had time-updated cumulative VCY <5 log10, the adjusted hazard ratio of multimorbidity was 1.99 (95% confidence interval [CI], 1.29–3.08) and 3.78 (95% CI, 2.17–6.58) for those with VCY 5–6.9 and ≥7 log10 copy-years/mL, respectively (P <.0001). Higher time-updated cumulative VCY increased the risk of each NACM. Conclusions Among ART-treated WWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence this may be a prognostically useful biomarker for NACM risk assessment in this population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for human immunodeficiency virus (HIV) management. Although studies have suggested associations between INSTIs and weight gain, women living with HIV (WLHIV) have been underrepresented in research. We evaluated the effect of switching or adding INSTIs among WLHIV. Methods Women enrolled in the Women's Interagency HIV Study (WIHS) from 2006–2017 who switched to or added an INSTI to ART (SWAD group) were compared to women on non-INSTI ART (STAY group). Body weight, body mass index (BMI), percentage body fat (PBF), and waist, hip, arm, and thigh circumferences were measured 6–12 months before and 6–18 months after the INSTI switch/add in SWAD participants, with comparable measurement time points in STAY participants. Linear regression models compared changes over time by SWAD/STAY group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen. Results We followed 1118 women (234 SWAD and 884 STAY) for a mean of 2.0 years (+/− 0.1 standard deviation [SD]; mean age 48.8 years, SD +/− 8.8); 61% were Black. On average, compared to the STAY group, the SWAD group experienced mean greater increases of 2.1 kg in body weight, 0.8 kg/m2 in BMI, 1.4% in PBF, and 2.0, 1.9, 0.6, and 1.0 cm in waist, hip, arm, and thigh circumference, respectively (all P values <.05). No differences in magnitudes of these changes were observed by INSTI type. Conclusions In WLHIV, a switch to INSTI was associated with significant increases in body weight, body circumferences, and fat percentages, compared to non-INSTI ART. The metabolic and other health effects of these changes deserve further investigation. [ABSTRACT FROM AUTHOR]

Study Question: Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone?Summary Answer: Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone.What Is Known Already: hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates.Study Design, Size, Duration: A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT).Participants/materials, Settings, Methods: One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment.Main Results and the Role Of Chance: One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m2 versus 23.7 kg/m2) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43-1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR= 1.98 (1.05-3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group.Limitations, Reasons For Caution: None.Wider Implications Of the Findings: The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely.Study Funding/competing Interest(s): The study was funded by TRIO Fertility. There are no conflicts of interest to declare.Trial Registration Number: ClinicalTrials.gov identifier: NCT02703584.Date Of Trial Registration: March 2016.Date Of First Patient's Enrollment: May 2016. [ABSTRACT FROM AUTHOR]

Background Anal cancer rates have increased, particularly in human immunodeficiency virus (HIV)–infected (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative women from the Atlanta Women's Interagency HIV Study cohort. Methods All participants underwent high-resolution anoscopy and anal cytology and had anal and cervical samples collected. Specimens were tested for 37 human papillomavirus (HPV) types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high-grade squamous intraepithelial lesion (A-HSIL) as the dependent variable. Results Seventy-five women were enrolled: 52 (69%) were HIV+ with three-fourths having undetectable viral load; 64 (86%) were black; mean age was 49 ± 8 years. Forty-nine (65%) anal cytology samples were abnormal, and 38 (51%) of anal samples were positive for at least 1 of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) anal samples and 19 (26%) cervical samples. In multivariate analyses, the odds of having A-HSIL were >6 times higher in women with anal hrHPV (adjusted odds ratio [aOR], 6.08 [95% confidence interval {CI}, 1.27–29.18], P =.02) and with positive cervical methylation (aOR, 6.49 [95% CI, 1.66–25.35], P =.007), but not significantly higher in women with positive anal methylation. Conclusions Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and at-risk HIV-negative women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed. [ABSTRACT FROM AUTHOR]

Background: The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT.Methods: Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT).Results: Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002).Conclusions: Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. [ABSTRACT FROM AUTHOR]

Background Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended first-line HIV treatment. We recently demonstrated increased weight gain associated with INSTI use among women living with HIV (WLH) enrolled in the Women's Interagency HIV Study (WIHS), raising concern for cardiometabolic consequences. We, therefore, evaluated the effects of INSTI use on lipids, insulin resistance, and glycemic control in WLH. Methods Data from 2008 to 2017 were analyzed from WLH enrolled in WIHS. Women who switched to or added an INSTI to ART (SWAD group) were compared with women who remained on non-INSTI ART (STAY group). Outcomes included changes in fasting total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and glucose; hemoglobin A1c; and incident insulin resistance (defined as homeostatic model assessment of insulin resistance [HOMA] score ≥2). Outcomes were measured 6–12 months before and 6–18 months after INSTI switch/add in the SWAD group with comparable time points in the STAY group. Linear regression models compared change over time in each outcome by SWAD/STAY group, adjusted for age, race, WIHS site, income, smoking status, statin use, and ART regimen at baseline. Results In total, 881 WIHS participants (182 SWAD and 699 STAY) were followed for a mean 1.8 (±1.1) years. Mean age was 49 (±8.8) years, BMI was 31 (±8.2) kg/m2, and 49% were Black. At baseline, SWAD vs. STAY was more likely to report NNRTI (vs. PI)-based ART and statin use (both P < 0.0001), but all baseline lipid and glucose variables were similar. Compared with STAY, the SWAD group experienced significantly greater decreases in HDL (−2.4 vs. +0.09 mg/dL, P = 0.03) and trended toward greater decreases in TC (−2.6 vs. −2.4 mg/dL, P = 0.07) at follow-up, without significant differences in TG or LDL. The SWAD group had significantly greater increases in A1c (+0.08% vs. −0.05%, P = 0.01) but trended toward lower incidence of insulin resistance (19% vs. 32%, P = 0.05). Conclusion Despite reported increases in weight, INSTI use was associated with only modest changes in lipid measurements and glycemic control during short-term follow-up of WLH compared with non-INSTI ART. Research is needed to elucidate long-term cardiometabolic effects. Disclosures Anandi N. Sheth, MD, MS, Gilead Sciences, Inc.: Research Grant. [ABSTRACT FROM AUTHOR]

Background Age-related non-AIDS comorbidities (NACM) increasingly account for morbidity and mortality in persons living with HIV. The burden of NACM and its association with HIV is poorly described in women. Methods We analyzed data from HIV+ and at-risk HIV− participants who were followed in the Women's Interagency HIV Study (WIHS) after 2009 (when >80% of participants used antiretroviral therapy). The prevalence of each NACM (defined by a combination of self-report, clinical measurements, and laboratory data) and the number of NACM were summarized at a most recent follow-up visit and were compared by age and HIV serostatus using unadjusted linear regression models. Results There were 3232 women (2309 HIV+, 923 HIV–) with a median follow-up of 15.3 years. The median age was 50 years, 65% were black, 38% currently smoked, 71% had ever used illicit drugs, 50% had annual income < $12,000, and median body mass index was 30 kg/m2. HIV+ women had a median CD4 count of 618 cells/mm3 and 66% had HIV viral suppression. Among 10 NACM evaluated, the following were more prevalent in HIV+ vs. HIV– women (all P < 0.01): psychiatric illness (57%/48%), liver disease (45%/26%), hyperlipidemia (40%/35%), bone disease (40%/33%), chronic kidney disease (15%/7%), and non-AIDS cancer (11%/7%). There was little difference in the prevalence of hypertension (66%/64%), lung disease (41%/43%), diabetes (22%/24%), and cardiovascular disease (19%/19%). Mean number of NACM was higher in HIV+ vs. HIV– women (3.6 vs. 3.0, P < 0.0001). Regardless of HIV serostatus, NACM burden significantly increased with age (P < 0.0001). Compared with women aged <40 of the same HIV serostatus, the estimated mean difference in NACM (HIV+/HIV–) for those 40–49, 50–59, ≥60 years was 1.1/0.7, 2.3/2.3, and 3.6/3.2, respectively (P < 0.0001 for all). Within-age-group comparisons revealed significantly greater NACM burden in HIV+ vs. HIV− women aged 40–49 years (P < 0.0001) and ≥60 years (P = 0.003), but not in those aged <40 or 50–59 years (HIV*age interaction P = 0.02) (figure). Conclusion NACM burden was high in both HIV+ and at-risk HIV– women, but higher in HIV+ women overall and in certain age groups. Accumulation of NACM has complex implications for clinical care, medication management, and healthcare screening that must be further examined in this population. Disclosures Anandi N. Sheth, MD, MS, Gilead Sciences, Inc.: Research Grant. [ABSTRACT FROM AUTHOR]

Background Public health information exchanges (HIEs) link real-time surveillance and clinical data and can help to re-engage out-of-care people with HIV (PWH). Methods We conducted a retrospective cohort study of out-of-care PWH who generated an HIE alert in the Grady Health System (GHS) Emergency Department (ED) between January 2017 and February 2018. Alerts were generated for PWH who registered in the GHS ED without Georgia Department of Public Health (GDPH) CD4 or HIV-1 RNA in the prior 14 months. The alert triggered a social work (SW)–led re-linkage effort. Multivariate logistic regression analyses used HIE-informed SW re-linkage efforts as the independent variable, and linkage to care and 3- and 6-month viral suppression (HIV-1 RNA < 200 c/mL) as primary outcomes. Patients admitted to the hospital were excluded from primary analysis. Results One hundred forty-seven out-of-care patients generated an alert. Ninety-eight were included in the primary analysis (mean age [SD], 41 ± 12 years; 70% male; 93% African American), and 20 received the HIE-informed SW intervention. Sixty percent of patients receiving the intervention linked to care in 6 months, compared with 35% who did not. Patients receiving the intervention were more likely to link to care (adjusted risk ratio [aRR], 1.63; 95% confidence interval [CI], 0.99–2.68) and no more likely to achieve viral suppression (aRR, 1.49; 95% CI, 0.50–4.46) than those who did not receive the intervention. Conclusions An HIE-informed, SW-led intervention systematically identified out-of-care PWH and may increase linkage to care for this important population. HIEs create an opportunity to intervene with linkage and retention strategies. [ABSTRACT FROM AUTHOR]

Background Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population. Methods The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit. Results There were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P <.0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P <.0001), each remaining significant in adjusted models. Conclusions This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level. [ABSTRACT FROM AUTHOR]

Background Gains in life expectancy through optimal control of HIV infection with antiretroviral therapy (ART) may be threatened if other comorbidities, such as diabetes, are not optimally managed. Methods We analyzed cross-sectional data of the Women's Interagency HIV Study (WIHS) from 2001, 2006, and 2015. We estimated the proportions of HIV-positive and HIV-negative women with diabetes who were engaged in care and achieved treatment goals (hemoglobin A1c [A1c] <7.0%, blood pressure [BP] <140/90 mmHg, low-density lipoprotein [LDL] cholesterol <100 mg/dL, not smoking) and viral suppression. Repeated-measures models were used to estimate the adjusted prevalence of achieving each diabetes treatment goal at each time point, by HIV status. Results We included 486 HIV-positive and 258 HIV-negative women with diabetes. In 2001, 91.8% visited a health care provider, 60.7% achieved the A1c target, 70.5% achieved the BP target, 38.5% achieved the LDL cholesterol target, 49.2% were nonsmokers, 23.3% achieved combined ABC targets (A1c, BP, and cholesterol), and 10.9% met combined ABC targets and did not smoke. There were no differences by HIV status, and patterns were similar in 2006 and 2015. Among HIV-positive women, viral suppression increased from 41% in 2001 to 87% in 2015 compared with 8% and 13% achieving the ABC goals and not smoking. Viral suppression was not associated with achievement of diabetes care goals. Conclusions Successful management of HIV is outpacing that of diabetes. Future studies are needed to identify factors associated with gaps in the HIV–diabetes care continuum and design interventions to better integrate effective diabetes management into HIV care. [ABSTRACT FROM AUTHOR]