Prevalence and correlates of restless legs syndrome in men living with HIV

Background Data on the prevalence and correlates of restless legs syndrome (RLS) in people with HIV are limited. This study sought to determine the prevalence of RLS, associated clinical correlates, and characterize sleep-related differences in men with and without HIV. Methods Sleep-related data were collected in men who have sex with men participating in the Multicenter AIDS Cohort Study (MACS). Demographic, health behaviors, HIV status, comorbidities, and serological data were obtained from the MACS visit coinciding with sleep assessments. Participants completed questionnaires, home polysomnography, and wrist actigraphy. RLS status was determined with the Cambridge-Hopkins RLS questionnaire. RLS prevalence was compared in men with and without HIV. Multinomial logistic regression was used to examine correlates of RLS among all participants and men with HIV alone. Sleep-related differences were examined in men with and without HIV by RLS status. Results The sample consisted of 942 men (56% HIV+; mean age 57 years; 69% white). The prevalence of definite RLS was comparable in men with and without HIV (9.1% vs 8.7%). In multinomial regression, HIV status was not associated with RLS prevalence. However, white race, anemia, depression, and antidepressant use were each independently associated with RLS. HIV disease duration was also associated with RLS. Men with HIV and RLS reported poorer sleep quality, greater sleepiness, and had worse objective sleep efficiency/ fragmentation than men without HIV/RLS. Conclusions The prevalence of RLS in men with and without HIV was similar. Screening for RLS may be considered among people with HIV with insomnia and with long-standing disease

Factors associated with syphilis seroprevalence in women with and at-risk for HIV infection in the Women's Interagency HIV Study (1994-2015)

Objective Syphilis rates among women in the USA more than doubled between 2014 and 2018. We sought to identify correlates of syphilis among women enrolled in the Women's Interagency HIV Study (WIHS) to inform targeted interventions. Methods The retrospective cross-sectional analysis of secondary data included women with HIV or at-risk of HIV who enrolled in the multisite US WIHS cohort between 1994 and 2015. Syphilis screening was performed at baseline. Infection was defined serologically by a positive rapid plasma reagin test with confirmatory treponemal antibodies. Sociodemographic and behavioural characteristics stratified by baseline syphilis status were compared for women enrolled during early (1994-2002) and recent (2011-2015) years. Multivariable binomial modelling with backward selection (p>0.2 for removal) was used to model correlates of syphilis. Results The study included 3692 women in the early cohort and 1182 women in the recent cohort. Syphilis prevalence at enrolment was 7.5% and 3.7% in each cohort, respectively (p100 lifetime sex partners (all p<0.05). In the recent cohort, age (adjusted prevalence OR (aPOR) 0.2, 95% CI 0.1 to 0.6 for 30-39 years; aPOR 0.5, 95% CI 0.2 to 1.0 for 40-49 years vs ≥50 years), hepatitis C seropositivity (aPOR 2.1, 95% CI 1.0 to 4.1) and problem alcohol use (aPOR 2.2, 95% CI 1.1 to 4.4) were associated with infection. Conclusions Syphilis screening is critical for women with HIV and at-risk of HIV. Targeted prevention efforts should focus on women with hepatitis C and problem alcohol use

Mortality under plausible interventions on antiretroviral treatment and depression in HIV-infected women: an application of the parametric g-formula

Purpose Among HIV-infected persons, antiretroviral therapy (ART) and depression are strongly associated with mortality. We estimated reductions in 5-year mortality in Women's Interagency HIV Study participants under plausible hypothetical increases in ART initiation and reductions in depression (CES-D score≥16). Methods We followed 885 ART-naïve Women's Interagency HIV Study participants for 5 years from their first study visit after April 1998 to death or censoring. We used the parametric extended g-formula to estimate cumulative mortality under the natural course (NC) and alternative exposure distributions. Results Baseline prevalence of depression was 52% and 62% initiated ART by 5 years. Compared with mortality under NC (13.2%), immediate ART and elimination of 36% or 67% of depressive episodes were associated with risk differences (RDs) of −5.2% (95% CI: −7.7%, −2.6%) and −5.7 (95% CI: −8.7, −2.7). Compared with immediate ART and NC for depression, additionally eliminating 67% of the depressive episodes was associated with RD = −1.6 (95% CI: −3.9, 0.8). Compared with 5-year mortality under NC for ART and elimination of 67% of depression, also initiating ART immediately was associated with RD = -2.6 (95% CI: -5.0, -0.3). Conclusions Increasing ART initiation and reducing depression were associated with moderate reductions in 5-year mortality among HIV-infected women

Recent abacavir use increases risk of type 1 and type 2 myocardial infarctions among adults with HIV

Background: There is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. Methods: Incident MIs in North American Cohort Collaboration on Research and Design participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude hazard ratio (HR) and adjusted hazard ratio (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately. A sensitivity analysis evaluated whether Framingham risk score (FRS) modified the effect of ABC on MI occurrence. Results: Eight thousand two hundred sixty-five adults who initiated antiretroviral therapy contributed 29,077 person-years and 123 MI events (65 T1MI and 58 T2MI). Median follow-up time was 2.9 (interquartile range 1.4-5.1) years. ABC initiators were more likely to have a history of injection drug use, hepatitis C virus infection, hypertension, diabetes, impaired kidney function, hyperlipidemia, low (,200 cells/mm3) CD4 counts, and a history of AIDS. The risk of the combined MI outcome was greater for persons who used ABC in the previous 6 months [aHR = 1.84 (1.17-2.91)]; and persisted for T1MI (aHR = 1.62 [1.01]) and T2MI [aHR = 2.11 (1.08-4.29)]. FRS did not modify the effect of ABC on MI (P = 0.14) and inclusion of FRS in the MSM did not diminish the effect of recent ABC use on the combined outcome. Conclusions: Recent ABC use was associated with MI after adjustment for known risk factors and for FRS. However, screening for T1MI risks may not identify all or even most persons at risk of ABC use-associated MIs

Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13–35) of these cancers and 37% (7–66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30–58) for cholesterol and 42% (28–56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17–48). For renal disease, the PAF was greatest for hypertension (39%; 26–51) followed by elevated total cholesterol (22%; 13–31), detectable HIV RNA (19; 9–31), and low CD4 cell count (13%; 4–21). Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk

Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Programs

Background. Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodefciency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods. We included HIV-infected individuals aged =16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-e?ect models were used to smooth trends in median CD4 cell counts. Results. A total of 951 855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/μL (95% confdence interval, 58-104/μL) to 287/μL (250-328/μL) in LICs, from 99/μL (71-140/μL) to 234/μL (192-285/μL) in LMICs, from 71/μL (49-104/μL) to 311/μL (255-379/μL) in UMICs, and from 161/μL (143-181/μL) to 327/μL (286-372/μL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions. Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional e?orts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART. © 2017 The Author(s)