From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/μL, and CD4 count at ART prescription increased from 160 to 364 cells/μL.
Recommendations for additional doses of COVID-19 vaccines for people with HIV (PWH) are restricted to those with advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk after vaccination among PWH is essential for informing vaccination guidelines.
Objective
To estimate the rate and risk of breakthrough infections among fully vaccinated PWH and people without HIV (PWoH) in the United States.
Design, Setting, and Participants
This cohort study used the Corona-Infectious-Virus Epidemiology Team (CIVET)-II (of the North American AIDS Cohort Collaboration on Research and Design [NA-ACCORD], which is part of the International Epidemiology Databases to Evaluate AIDS [IeDEA]), collaboration of 4 prospective, electronic health record–based cohorts from integrated health systems and academic health centers. Adult PWH who were fully vaccinated prior to June 30, 2021, were matched with PWoH on date of full vaccination, age, race and ethnicity, and sex and followed up through December 31, 2021.
Exposures
HIV infection.
Main Outcomes and Measures
COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after a patient was fully vaccinated.
Results
Among 113 994 patients (33 029 PWH and 80 965 PWoH), most were 55 years or older (80 017 [70%]) and male (104 967 [92%]); 47 098 (41%) were non-Hispanic Black, and 43 218 (38%) were non-Hispanic White. The rate of breakthrough infections was higher in PWH vs PWoH (55 [95% CI, 52-58] cases per 1000 person-years vs 43 [95% CI, 42-45] cases per 1000 person-years). Cumulative incidence of breakthroughs 9 months after full vaccination was low (3.8% [95% CI, 3.7%-3.9%]), albeit higher in PWH vs PWoH (4.4% vs 3.5%; log-rankP < .001; risk difference, 0.9% [95% CI, 0.6%-1.2%]) and within each vaccine type. Breakthrough infection risk was 28% higher in PWH vs PWoH (adjusted hazard ratio, 1.28 [95% CI, 1.19-1.37]). Among PWH, younger age (<45 y vs 45-54 y), history of COVID-19, and not receiving an additional dose (aHR, 0.71 [95% CI, 0.58-0.88]) were associated with increased risk of breakthrough infections. There was no association of breakthrough with HIV viral load suppression, but high CD4 count (ie, ≥500 cells/mm3) was associated with fewer breakthroughs among PWH.
Conclusions and Relevance
In this study, COVID-19 vaccination, especially with an additional dose, was effective against infection with SARS-CoV-2 strains circulating through December 31, 2021. PWH had an increased risk of breakthrough infections compared with PWoH. Expansion of recommendations for additional vaccine doses to all PWH should be considered.
Summary Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age‐related conditions. Therefore, we conducted a cross‐sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999–2002 surveys). Sample‐weighted linear regression analyses were conducted to assess age‐adjusted and multivariable‐adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (β continuous per § IQR = −61, p = 0.04; free estradiol β continuous per § IQR = −67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol‐induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.
To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015.In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL.Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories.Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.
Prolonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels. Among 1804 postmenopausal women enrolled in the Women's Health Initiative Observational Study, 15 serum oestrogens/oestrogen metabolites were quantified using liquid chromatography–tandem mass spectrometry. Physical activity and sitting were self-reported via questionnaire. Using baseline, cross-sectional data, geometric means (GM) of oestrogens/oestrogen metabolites (pmol l−1) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use. Longer time spent sitting (⩾10 vs ⩽5h per day) was associated with higher levels of unconjugated oestrone, independent of moderate- to vigorous-intensity physical activity and body mass index, among both never/former (GM=70.6 vs 57.7) and current MHT users (GM=242 vs 179) (P-trend ⩽0.03). Among never/former MHT users, sitting (⩾10 vs ⩽5h per day) was positively associated with 2-methoxyestradiol (GM=16.4 vs 14.4) and 4-methoxyestradiol (GM=2.36 vs 1.98) (P-trend ⩽0.04), independent of parent oestrogens. Inverse associations between moderate- to vigorous-intensity physical activity (⩾15 vs 0 metabolic equivalent task-hours per week) and parent oestrogens were found as expected. After adjustment for parent oestrogens, physical activity was not associated with oestrogen metabolites. Our data suggest that prolonged sitting and lower moderate- to vigorous-intensity physical activity are associated with higher levels of postmenopausal oestrogens/oestrogen metabolites, the oestrogen metabolism patterns that have previously been associated with higher endometrial and breast cancer risk.
Abstract OBJECTIVE: Oral contraceptive (OC) use is common in the United States and high-profile articles have renewed research interest in OC use and cancer risk. Several mechanisms have been proposed to explain how OC use influences postmenopausal cancer risk; one of the leading hypotheses is that OC use fundamentally alters feedback in the hypothalamic-pituitary-gonad axis, leading to long term changes in sex steroid hormone metabolism. However, women who use OCs are also unique with respect to factors that may affect both hormone metabolism and cancer risk. No studies have comprehensively commented on hormone levels in postmenopausal women who did and did not use OCs. DESIGN: We examined differences in circulating markers of sex steroid hormone metabolism associated with prior use of OCs among a subcohort of postmenopausal women from the Women’s Health Initiative Observational Study (983 women with at least one intact ovary and not currently using menopausal hormone therapy). MATERIALS AND METHODS: Using highly sensitive liquid chromatography–tandem mass spectrometry assays, we measured over 30 markers of estrogen and androgen metabolism in study serum samples. We used linear regression (adjusted and weighted) to estimate geometric mean hormone levels, which were then converted into relative percent differences. We controlled for potential confounders and stratified by: lifetime ovulatory cycles, body mass index, and parity (the focus of this abstract). RESULTS: Women with a history of OC use (n=346) had lower levels of estrogen metabolites than women who never used OCs (n=637), particularly when limiting this comparison among parous women (n=158 nulliparous women, n=825 parous women). In parous women, OC use was associated with reductions in total estrone (-18.5%, 95% confidence interval [CI] -31.1, -3.7%) and in estrogen metabolism overall: 2-hydroxylation metabolites were reduced by -18.5% (CI -28.2, -7.7%), 4-hydroxylation metabolites by -19.9% (CI -29.4, -9.1%), and 16-alpha-hydroxylation metabolites by -24.0% (CI -34.2, -12.2%). Hormone differences associated with OC use among nulliparous women were imprecise. When we made comparisons to nulliparous women who did not use OCs, women who both used OCs and were parous had lower testosterone (-21.2%, CI -33.1, -7.2%) and higher dihydrotestosterone relative to testosterone (its metabolic precursor; 16.5%, CI% -0.6, 36.6). However, aside from lower total estrone (-25.5%, CI -44.6, 0.2%), estrogen metabolism was not different between these groups. CONCLUSIONS: We saw evidence suggesting estrogen metabolism, as reflected in circulating markers, may be lower in postmenopausal women who previously used OCs. These effects were strongest among parous women, likely due to sufficient sample size, rather than any synergistic effect attributable to both using OCs and giving birth. These results support the idea that OC users have lower estrogen levels, but this should be evaluated in other age groups, as differences in hormone metabolism early in the lifecourse may lead women to use OCs. Citation Format: Kara A. Michels, Sally B. Coburn, Garnet Anderson, Louise A. Brinton, Chu Chen, Roni T. Falk, Margery L. Gass, Ashley M. Geczik, JoAnn E. Manson, Ruth M. Pfeiffer, Kerryn Reding, Gloria E. Sarto, Nicolas Wentzensen, Robert A. Wild, Xia Xu, Britton Trabert. Oral contraceptive use and postmenopausal sex steroid hormone metabolism [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO029.
Abstract Background The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)–specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. Methods Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age <50 or ≥50 years, race/ethnicity, HIV-1 RNA ≤500 or >500 copies/mL, CD4 count <350 or ≥350 cells/µL, and years 1999–2009 or 2010–2018. Because mortality rates have decreased over time, the final model was limited to 2010–2018. Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.
Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity ( n = 8) or bed rest alone ( n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum α- and γ-tocopherol and urinary 4-pyridoxic acid decreased ( P < 0.001) and plasma β-carotene increased ( P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit ( P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.
Anal cancer risk is elevated among people with HIV. Recent anal cancer incidence patterns among people with HIV in the United States and Canada remain unclear. It is unknown how the incidence patterns may evolve.
