Lipid changes due to tenofovir alafenamide are reversible by switching back to tenofovir disoproxil fumarate Objective: The aim of the present study is to assess the effect of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on lipids in patients switching from TDF to TAF and back. Methods: Retrospective data collection on patients who were initially switched from TDF to TAF and switched back to TDF after generics of TDF became available. Results: In total 385 patients were included. Median duration of TDF exposure before switch was 317 weeks (IQR 172–494). After switching from TDF to TAF mean total cholesterol (TC) increased from 186 ± 37 mg/dl at baseline to 206 ± 43 mg/dl and 204 ± 43 mg/dl at weeks 12 and 24 (p < 0.001). The increase in TC was mainly due to an increase in LDL-cholesterol. However ratio of TC/HDL remained unchanged indicating a simultaneous rise of LDL and HDL cholesterol. Baseline triglycerides increased from mean 153 ± 96 mg/dl to 176 ± 120 mg/dl and 176 ± 124 mg/dl at week 12 and 24 (p < 0.001). From 385 patients 168 were switched back from TAF to TDF after median duration on TAF of 96 weeks (IQR 89–104). At switching back from TAF to TDF mean TC was 202 ± 40 mg/dl and decreased at week 12 and 24 to 183 ± 41 mg/dl and 185 ± 35 mg/dl (p < 0.001). Mean triglycerides were 163 ± 119 mg/dl and decreased to 145 ± 108 mg/dl and 157 ± 112 mg/dl, respectively (p < 0.05). Patients with higher increases in TC after switching from TDF to TAF also showed more pronounced decreases after switching back. Conclusions: The results demonstrate a reversible effect on lipids of switching from TDF to TAF and back. Correspondence to Stefan Mauss, Center for HIV and Hepatogastroenterology Humboldt Strasse 18; 40237 Duesseldorf, Germany;. E-mail: stefan.mauss@center-duesseldorf.de Received 28 May, 2019 Revised 18 July, 2019 Accepted 22 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Non-AIDS comorbidity burden differs by sex, race, and insurance type in aging adults in HIV care Objective: To understand the epidemiology of non-AIDS-related chronic comorbidities (NACMs) among aging persons with HIV (PWH) Design: Prospective multicenter observational study to assess, in an age stratified fashion, number and types of NACMs by demographic and HIV factors. Methods: Eligible participants were seen during 1/1/1997 - 6/30/2015, followed >5.0 years, received antiretroviral therapy (ART), and virally suppressed [HIV viral load (VL) < 200 copies/mL ≥75% of observation time]. Age was stratified (18–40, 41–50, 51–60, ≥61 years). NACMs included cardiovascular disease, cancer, hypertension, diabetes, dyslipidemia, arthritis, viral hepatitis, anemia, and psychiatric illness. Results: Of 1540 patients, 1247 (81%) were men, 406 (26%) non-Hispanic blacks (NHB), 183 (12%) Hispanics/Latinos, 575 (37%) with public insurance, 939 (61%) men who have sex with men (MSM), and 125 (8%) with injection drug use history. By age strata 18–40, 41–50, 51–60, ≥61 years, there were 180, 502, 560, and 298 patients, respectively. Median HIV Outpatient Study (HOPS) observation was 10.8 years (range: min-max = 5.0–18.5). Mean number of NACMs increased with older age category; 1.4, 2.1, 3.0, and 3.9, respectively (P < 0.001), as did prevalence of most NACMs (P < 0.001). Age-related differences NACM number were primarily due to anemia, hepatitis C virus infection, and diabetes. Differences (all P < 0.05) in NACM number existed by sex (women >men, 3.9 vs 3.4), race/ethnicity (NHB >non-NHB, 3.8 vs 3.4), and insurance status (public >private, 4.3 vs 3.1). Conclusions: Age-related increases existed in prevalence and number of NACMs, with disproportionate burden among women, NHBs, and the publicly insured. These groups should be targeted for screening and prevention strategies aimed at NACM reduction. Correspondence to Frank J, Palella Jr, MD, Feinberg School of Medicine, Northwestern University, NMH/Feinberg Room 13-502, 251 E Huron, Chicago IL 60611. E-mail: f-palella@northwestern.edu Received 17 December, 2018 Revised 1 May, 2019 Accepted 26 May, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Progress toward HIV epidemic control in lesotho: results from a population-based survey Objective: The Lesotho Population-based HIV Impact Assessment (LePHIA) survey was conducted nationally and designed to measure HIV prevalence, incidence, and viral load suppression (VLS). Design: A nationally representative sample of 9,403 eligible households was surveyed between November 2016 and May 2017; analyses account for study design. Consenting participants provided blood samples, socio-demographic and behavioral information. Methods: Blood samples were tested using the national rapid HIV testing algorithm. HIV-seropositive results were confirmed with Geenius supplemental assay. Screening for detectable concentrations of antiretroviral (ARV) analytes was conducted on dried blood specimens from all HIV-positive adults using high-resolution liquid chromatography coupled with tandem mass spectrometry. Self-reported and/or ARV biomarker data were used to classify individuals as HIV-positive and on treatment. Viral load testing was performed on all HIV-positive samples at central labs. VLS was defined as HIV RNA < 1000 copies per mL. Results: Overall, 25.6% of adults ages 15–59 were HIV-positive. Among seropositive adults, 81.0% (male: 76.6%, female: 84.0%) reported knowing their HIV status, 91.8% of people living with HIV (male: 91.6%, female: 92.0%) who reported knowing their status reporting taking ARVs, and 87.7% (male and female: 87.7%) of these had VLS. Younger age was significantly associated with being less likely to be aware of HIV status for both sexes. Conclusions: Findings from this population-based survey provide encouraging data in terms of HIV testing and treatment uptake and coverage. Specific attention to reaching youth to engage them in HIV-related intervention is critical to achieving epidemic control. Correspondence to Amee Schwitters, US Centers for Disease Control, Division of Global HIV & TB, 1600 Clifton Road, NE, Atlanta, GA 30329. Tel: +1 404 718 8583; e-mail: Efn6@cdc.gov Received 14 May, 2019 Revised 23 July, 2019 Accepted 26 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Adverse childhood experiences, sexual debut and HIV testing among adolescents in a low-income high HIV-prevalence context Objectives: To investigate whether adverse childhood experiences (ACEs) are important determinants of sexual debut and HIV testing. Design: Adolescents (age 10-16; N = 2,089) from rural Malawi were interviewed in 2017-2018 for the baseline wave of a longitudinal study of childhood adversity and HIV risk. Methods: Respondents were interviewed in their local language. Surveys captured 13 lifetime childhood adversities (using the ACE – International Questionnaire); sexual debut; and previous HIV testing. We used multivariate regression models to test whether adversity, measured both cumulatively and separately, predicted HIV risk. Results: For each additional adversity, there was a significant rise in the odds of sexual debut (OR 1.13, CI 1.07–1.20) and HIV testing (OR 1.10, CI 1.04–1.16). Conclusions: Preventing HIV among all young people necessitates a paradigm shift that recognizes the importance of early life social determinants in structuring HIV risk. Correspondence to Rachel Kidman, Program in Public Health and Department of Family, Population and Preventive Medicine HSC Level 3, Room 79 Stony Brook University (State University of New York) Stony Brook, NY 11794. Tel: +631 444 2645; e-mail: rachel.kidman@stonybrook.edu Received 24 June, 2019 Revised 31 July, 2019 Accepted 2 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Comorbidity and polypharmacy among women living with HIV in British Columbia Objective: To characterize comorbid disease and medication burden among women living with HIV (WLWH) in British Columbia (BC), Canada. Design: We examined baseline data from 267 WLWH and 276 HIV-negative females, ≥19 years, enrolled in the Children and Women: Antiretrovirals and Markers of Aging (CARMA) cohort. Methods: Self-reported demographic, medical condition, medication, vitamin, and substance exposure data were collected at baseline CARMA study visits. We considered conditions with appropriate concomitant medications to be “treated”. Wilcoxon rank-sum and Fisher's exact tests compared continuous and categorical variables between WLWH and HIV-negative women. Number of diagnoses, prescribed medications (excluding HIV/antiretrovirals), vitamins, and prevalence of depression/anxiety/panic disorder were compared using negative binomial and logistic regressions for continuous and binary variables respectively. Results: WLWH were younger (median [IQR] 39.9 [33.6-46.9] vs 43.6 [31.8–54.6] years, p = 0.01), attained lower education (40.5% vs 69.6% college/university, p < 0.001), and more often currently smoked tobacco (47.9% vs 31.9%, p < 0.001), or had income <$15,000/year (49.0% vs 43.1%, p < 0.001). Although younger, and despite omitting HIV infection, WLWH had a greater number of diagnoses (IRR [95%CI] 1.58 [1.38–1.81], p <0.001), and more depression/anxiety/panic disorder versus controls (OR [95% CI], 1.86 [1.22–2.83], p = 0.004). Our model predicts that with mean BMI (26.3), WLWH and HIV-negative peers would have two comorbid diagnoses by age 30 and 60, respectively. Conclusions: WLWH living in BC have more comorbid illness earlier in life than their HIV-negative peers, and have very high rates of depression/anxiety/panic disorder. Addressing mental health and comorbid conditions is essential to improving health outcomes among WLWH. Correspondence to Dr. Melanie C.M. Murray, E600B – 4500 Oak Street, Vancouver, BC, Canada, V6H 3N1. Tel: +(604) 875 2212; fax: +(604) 875 3063; e-mail: Melanie.Murray@cw.bc.ca Received 30 April, 2019 Revised 31 July, 2019 Accepted 6 August, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

High yield of new HIV diagnoses during active case-finding for tuberculosis Objective: To evaluate the utility of a broad and non-specific symptom screen for identifying people with undiagnosed HIV infection. Design: Secondary analysis of operational data collected during implementation of a cluster-randomized trial for tuberculosis case detection. Methods: As part of the trial, adults reporting cough, fever, night sweats, weight loss, or difficulty breathing of any duration in the past month were identified in health facilities and community-based mobile screening units in western Kenya. Adults reporting any symptom were offered HIV testing. We analysed the HIV testing data from this study, using modified Poisson regression to identify predictors of new HIV diagnoses among adults with symptoms and initially unknown HIV status. Results: We identified 3,818 symptomatic adults, referred 1424 (37%) for testing, of whom 1065 (75%) accepted, and 107 (10%) were newly diagnosed with HIV. The prevalence of new HIV diagnoses was 21% (95% CI: 17–25%) among those tested in health facilities and 5% (95% CI 4–7%) among those tested in mobile units. More men were diagnosed with HIV than women despite fewer men being screened. People who reported 4–5 symptoms were over twice as likely to be diagnosed with HIV compared to those reporting 1–3 symptoms (adjusted prevalence ratio [aPR] in health facilities = 2.58, 95% CI, 1.65–4.05; aPR in mobile units = 2.63, 95% CI, 1.37–5.03). Conclusion: We observed a high yield of new HIV diagnoses among adults identified by active application of a broad symptom screen. Integrated tuberculosis and HIV screening using could help close the detection gap for both conditions. Correspondence to Kevin P. Cain, CDC Tanzania, 2448 Luthili Rd, NIMR Complex, Dar es Salaam, Tanzania. E-mail: bvz1@cdc.gov Received 24 May, 2019 Revised 2 August, 2019 Accepted 13 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Racial/Ethnic and HIV risk category disparities in PrEP discontinuation among patients in publicly-funded primary care clinics Objective: Dissemination of pre-Exposure Prophylaxis (PrEP) is a priority for reducing new HIV infections, especially among vulnerable populations. However, there are limited data available on PrEP discontinuation following initiation, an important component of the PrEP cascade. Design: Patients receiving PrEP within the San Francisco Department of Public Health Primary Care Clinics (SFPCC) are included in a PrEP registry if they received a PrEP prescription, were not receiving post-exposure prophylaxis, and not known to be HIV positive. Methods: We calculated PrEP discontinuation for patients initiating PrEP at any time from January 2012 to July 2017 and evaluated their association with demographic and risk variables using Cox regression analysis. Results: Overall, 348 patients received PrEP over the evaluation period. The majority (84%) were men, and the cohort was racially/ethnically diverse. The median duration of PrEP use was 8.3 months. In adjusted analysis, PrEP discontinuation was lower among older patients (aHR 0.89; 95% CI: 0.80–0.99; p = 0.03); but higher among Black patients (compared with White patients) (aHR 1.87; 95%CI: 1.27–2.74; p = 0.001), patients who inject drugs (aHR 4.80; 95%CI 2.66–8.67; p < 0.001), and transgender women who have sex with men (compared with men who have sex with men) (aHR 1.94; 95%CI: 1.36–2.77; p < 0.001). Conclusion: Age, racial/ethnic, and risk category disparities in PrEP discontinuation were identified among patients in a public-health funded primary care setting. Further efforts are needed to understand and address PrEP discontinuation among priority populations to maximize the preventive impact of PrEP, and reverse HIV-related disparities at a population level. Correspondence to Hyman M. Scott, 25 Van Ness Ave, Suite 100, San Francisco, CA 94102. Tel: +415 437 7483; e-mail: hyman.scott@sfdph.org Received 26 April, 2019 Revised 12 June, 2019 Accepted 14 June, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Better executive function is independently associated with full HIV suppression during combination therapy Objective: HIV-associated neurocognitive impairment continues to be prevalent and clinically relevant. We examined the relationship between neurocognition and full plasma HIV RNA suppression among study participants over a 15 year period at a large research program. Design/Methods: We analyzed the combined prospective studies of the HIV Neurobehavioral Research Program (HNRP) at the University of California at San Diego. Participants were eligible for analysis if on three drug cART with comprehensive neuropsychological testing results. Participants who reported recent non-adherence were excluded. The primary outcome was plasma HIV RNA of ≤50 copies/ml. Generalized estimating equation was used to assess for associations with full virologic suppression taking into account longitudinal visits. Results: There were 1943 participants at baseline, of whom 69.4% had plasma HIV RNA ≤50 copies/ml. Participants with full suppression were slightly older, less likely to abuse cocaine, and had significantly better executive function. Multivariate analysis with incorporation of longitudinal visits (total = 5555) confirmed current cocaine abuse to be strongly associated with lack of virologic suppression (odds ratio = 0.45, 95% confidence interval = 0.31–0.63). In contrast, increasing age, increasing years of HIV infection, and increasing executive function (odds ratio = 1.18 for T score change of 10, 95% confidence interval = 1.07–1.30) were associated with full virologic suppression. Lack of virologic suppression at baseline was associated with a significant subsequent decline in executive function. Conclusions: In a 15 year research cohort of almost 2000 HIV-infected individuals on cART, better executive function was associated with full virologic suppression, possibly as a result rather than a cause. Correspondence to Albert M. Anderson, MD, MHS, Emory University School of Medicine, Atlanta, United States. e-mail: aande2@emory.edu Received 15 March, 2019 Revised 8 July, 2019 Accepted 24 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Cannabinoids and inflammation: Implications for People Living with HIV Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies. Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons. Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the phytocannabinoids which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators. CB2 receptor activation has been shown in vitro to reduce CD4 T-cell infection by CXCR4-tropic HIV and to reduce HIV replication. Studies involving SIV-infected macaques have shown that Δ9-THC can reduce morbidity and mortality and has favourable effects on the gut mucosal immunity. Furthermore, Δ9-THC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques. In humans, cannabis use does not induce a reduction in peripheral CD4 T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokines secretion, all of which are related to HIV disease progression and co-morbidities. Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART. Correspondence to Cecilia T. Costiniuk, Dr, Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec Canada, Royal Victoria Hospital: Glen Site; 1001 boulevard Decarie, Montreal, Quebec, H4A 3J1. Tel: +14-843-2090; fax: +514-843-2092; e-mail: cecilia.costiniuk@mcgill.ca Received 6 August, 2019 Accepted 8 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Social Harms in Female-INITIATED hiv prevention method RESEARCH: state of the evidence Objectives: Assessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for “social harms” (SH), generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on SH within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts. Methods: Secondary analysis of quantitative data from three randomized, double-blind, placebo-controlled trials of microbicide candidates in sub-Saharan Africa was conducted. Additionally, we assessed data from two prospective cohort studies that included participants who became HIV-positive or pregnant during parent trials. Results: SH reporting was low across the largest and most recent microbicide studies. SH incidence per 100 person-years ranged from 1.10 (95% CI: 0.78–1.52) to 3.25 (95% CI: 2.83–3.74) in the phased trials. Reporting differed by dosing mechanism (e.g. vaginal gel, oral tablet, ring) and study, most likely as a function of measurement differences. SH were most frequently associated with male partners, rather than, for example, experiences of stigma in the community. Conclusions: Measurement and screening for SH is an important component of conducting ethical research of novel HIV prevention methods. To date SH incidence reported in microbicide trials has been relatively low (<4% per 100py), and the majority have been partner-related events. However, any incidence of SH within the context of HIV prevention is important to capture and understand for the safety of individual women, and for the successful impact of prevention methods in a real-world context. Correspondence to Elizabeth T. Montgomery, E-mail: emontgomery@rti.org Received 28 February, 2019 Revised 12 July, 2019 Accepted 19 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.