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.
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.
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.
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.
Early HIV studies suggested protective associations of overweight against mortality, yet data are lacking for the era of potent highly active antiretroviral therapy (HAART). We evaluated associations ...of pre-HAART initiation body mass index (BMI) with mortality among HAART-using women.
Prospective study of time to death after HAART initiation among continuous HAART users in the Women's Interagency HIV Study. Unadjusted Kaplan-Meier and adjusted proportional hazards survival models assessed time to AIDS and non-AIDS death by last measured pre-HAART BMI.
Of 1428 continuous HAART users 39 (2.7%) were underweight, 521 (36.5%) normal weight, 441 (30.9%) overweight, and 427 (29.9%) obese at time of HAART initiation. A total of 322 deaths occurred during median follow-up of 10.4 years (IQR 5.9-14.6). Censoring at non-AIDS death, the highest rate of AIDS death was observed among underweight women (p = 0.0003 for all 4 categories). In multivariate models, women underweight prior to HAART died from AIDS more than twice as rapidly vs. normal weight women (aHR 2.04, 95% CI 1.03, 4.04); but being overweight or obese (vs. normal weight) was not independently associated with AIDS death. Cumulative incidence of non-AIDS death was similar across all pre-HAART BMI categories.
Among continuous HAART-using women, being overweight prior to initiation was not associated with lower risk of AIDS or non-AIDS death. Being underweight prior to HAART was associated with over double the rate of AIDS death in adjusted analyses. Although overweight and obesity may be associated with many adverse health conditions, neither was predictive of mortality among the HAART-using women.
Research is scant regarding differential effects of specific types of recreational drugs use on antiretroviral therapy adherence among women, particularly to single-tablet regimens (STR). This is ...increasingly important in the context of marijuana legalization. We examined the effects of self-reported substance use on suboptimal (<95%) adherence in the Women’s Interagency HIV Study, 2003–2014. Among 1799 HIV-infected women, the most prevalent substance used was marijuana. In multivariable Poisson GEE regression, substance use overall was significantly associated with suboptimal adherence (adjusted prevalence ratio, aPR = 1.20, 95% CI 1.10–1.32), adjusting for STR use, socio-demographic, behavioral, and clinical factors. Among STR users, compared to no drug use, substance use overall remained detrimental to ART adherence (aPR = 1.61, 95% CI 1.24–2.09); specifically, both marijuana (aPR = 1.48, 95% CI: 1.11–1.97) and other drug use (aPR = 1.87, 95% CI 1.29–2.70) predicted suboptimal adherence. These findings highlight the need to intervene with drug-using women taking antiretroviral therapy to maintain effective adherence.
Lifestyle improvements are key modifiable risk factors for Type 2 diabetes mellitus (DM) however specific influences of biologically active dietary metabolites remain unclear. Our objective was to ...compare non-targeted plasma metabolomic profiles of women with versus without confirmed incident DM. We focused on three lipid classes (fatty acyls, prenol lipids, polyketides).
Fifty DM cases and 100 individually matched control participants (80% with human immunodeficiency virus HIV) were enrolled in a case-control study nested within the Women's Interagency HIV Study. Stored blood samples (1-2 years prior to DM diagnosis among cases; at the corresponding timepoint among matched controls) were assayed in triplicate for metabolomics. Time-of-flight liquid chromatography mass spectrometry with dual electrospray ionization modes was utilized. We considered 743 metabolomic features in a two-stage feature selection approach with conditional logistic regression models that accounted for matching strata.
Seven features differed by DM case status (all false discovery rate-adjusted q<0.05). Three flavonoids (two flavanones, one isoflavone) were respectively associated with lower odds of DM (all q<0.05), and sorbic acid was associated with greater odds of DM (all q<0.05).
Flavonoids were associated with lower odds of incident DM while sorbic acid was associated with greater odds of incident DM.
Abstract
Background
Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus .
Methods
We evaluated the ...relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8+CD38+DR+) and CD4 (CD4+CD38+DR+) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10.
Results
Ten HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, −6.6% P = .002; CD4 T cells, −2.7% P = .007), C*18:01 (CD8 T cells, −6.6%; P < .0008) and DRB1*13:01 (CD4 T cells, −2.7%; P < .0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P < .0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03.
Conclusion
These findings suggest that a person’s HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.
We found that specific HLA alleles predict CD8 and CD4 T-cell activation, independent of HLA associations with viral load. These findings suggest that host genetic variation could affect risk for end-organ diseases through an immune activation mechanism.
Abstract
In 1984, a large prospective study of the natural history of human immunodeficiency virus (HIV) infection, the Multicenter AIDS Cohort Study (MACS), was established; 10 years later, the ...Women’s Interagency HIV Study (WIHS) was launched. Motivated by the merger and redesign of these long-standing HIV cohort studies in 2019, we review ways in which HIV epidemiology in the United States has transformed over the lives of these studies and how this evolution has influenced planning for enrollment and follow-up. We highlight changes that have occurred in the 3 major domains that are central to epidemiologic science: changes to key populations at highest risk for HIV, refinements in measurement and shifts in the outcomes of interest, and a new era in the tools and approaches that epidemiologists use to synthesize evidence from measurements made on populations. By embracing foundational principles with modern methods, the epidemiologic approach of analyzing the causes and distributions of diseases in contemporaneous populations will continue to advance HIV science over the next decade.
OBJECTIVE: To study the correlation between circulating 25-hydroxyvitamin D (25OH-D) levels and serum antimüllerian hormone (AMH) in women enrolled in the Women's Interagency HIV Study. DESIGN: ...Cross-sectional study. SETTING: None. PATIENT(S): All premenopausal women (n = 388) with regular menstrual cycles were included and subdivided into three groups: group 1 with age <35 years (n = 128), group 2 with age 35–39 years (n = 119), and group 3 with age ≥40 years (n = 141). INTERVENTION(S): Serum for 25OH-D, AMH, fasting glucose and insulin, and creatinine levels. MAIN OUTCOME MEASURE(S): Correlation between 25OH-D and AMH before and after adjusting for HIV status, body mass index, race, smoking, illicit drug use, glucose and insulin levels, estimated glomerular filtration rate, and geographic site of participation. RESULT(S): After adjusting for all covariates, the regression slope in all participants for total 25OH-D predicting log₁₀AMH for 25-year-olds (youngest participant) was −0.001 (SE = 0.008); and for 45-year-olds (oldest participant) the corresponding slope was +0.011 (SE = 0.005). Fasting insulin level was negatively correlated with serum AMH. The regression slope for the correlation between 25OH-D and AMH in group 1 was +0.002 (SE = 0.006); in group 2 was +0.006 (SE = 0.005); and in group 3 was +0.011 (SE = 0.005). There was no association between HIV and AMH. CONCLUSION(S): A novel relationship is reported between circulating 25OH-D and AMH in women aged ≥40 years, suggesting that 25OH-D deficiency might be associated with lower ovarian reserve in late-reproductive-aged women.
To compare serum müllerian inhibiting substance (MIS) levels between white, black, and Hispanic women to determine whether ovarian aging occurs at a different time course for women of different ...racial groups.
Longitudinal study of serum MIS levels in women of different race and ethnicity over two different time points.
Women's Interagency HIV Study, a multicenter prospective cohort study.
Serum samples obtained from 809 participants (122 white, 462 black, and 225 Hispanic women).
Comparison of serum MIS between women of different race and ethnicity at two time points (median age 37.5 years and 43.3 years).
Variation in MIS by race and ethnicity over time, controlling for age, body mass index, HIV status, and smoking.
Compared with white women, average MIS values were lower among black (25.2% lower) and Hispanic (24.6% lower) women, adjusting for age, body mass index, smoking, and HIV status.
There is an independent effect of race and ethnicity on the age-related decline in MIS over time.
Among women in the United States, non-Latina black women in the South have disproportionately high rates of new HIV infections but low use of pre-exposure prophylaxis (PrEP). Effective strategies to ...identify factors associated with PrEP eligibility could facilitate improved screening, offering, and uptake of PrEP among US women at risk of HIV.
We applied 2014 CDC criteria for PrEP use to at-risk HIV-negative women enrolled in the Southern US sites (Atlanta, Chapel Hill, Birmingham/Jackson, Miami) of the Women's Interagency HIV Study from 2014 to 2015 to estimate PrEP eligibility and assess PrEP knowledge and acceptability. Factors associated with PrEP eligibility were assessed using multivariable models.
Among 225 women, 72 (32%) were PrEP-eligible; the most common PrEP indicator was condomless sex. The majority of PrEP-eligible women (88%) reported willingness to consider PrEP. Only 24 (11%) PrEP-eligible women had previously heard of PrEP, and only 1 reported previous use. Education level less than high school adjusted odds ratio (aOR) 2.56; 95% confidence interval (CI): 1.22 to 5.37, history of sexual violence (aOR 4.52; 95% CI: 1.52 to 17.76), and medium to high self-perception of HIV risk (aOR 6.76; 95% CI: 3.26 to 14.05) were significantly associated with PrEP eligibility in adjusted models.
Extremely low PrEP awareness and use despite a high proportion of eligibility and acceptability signify a critical need to enhance PrEP education and delivery for women in this region. Supplementing CDC eligibility criteria with questions about history of sexual violence and HIV risk self-assessment may enhance PrEP screening and uptake among US women.
The prevalence and burden of age-related non-AIDS comorbidities (NACMs) are poorly characterized among women living with HIV (WLWH).
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.
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.
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.
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