Delayed GALT reconstitution in duodenum compared to rectum in hiv-infected patients initiating antiretroviral therapy Background: We aimed to characterize the impact of ART initiation on GALT at various sites along the gastrointestinal site. Methodology: Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV- and 33 treatment-naïve HIV+ subjects at baseline and after 9-months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. Results: Twenty-six HIV+ subjects completed follow-up. The lowest reconstitution of CD4+ T-cells and the lowest CD4/CD8 ratio during ART compared to blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T-cells (Treg) were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in LTA levels, which reflects gram-positive bacterial translocation, correlated with increases in %CD4+ T-cells in duodenum (Rho 0.773, P = 0.033), and with decreases duodenal Treg populations (Rho -0.40, P = 0.045). Conclusions: HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with gram positive bacteria. Correspondence to David M. Asmuth, University of California Davis Medical Center, Sacramento, CA United States. Tel: +916 734 8695; fax: +916 734 7766; e-mail: dasmuth@ucdavis.edu, Sergio Serrano-Villar, University Hospital Ramón y Cajal, Madrid, Spain. Tel: +34 91 336 8975; e-mail: Sergio.serrano@salud.madrid.org Received 10 February, 2019 Revised 29 May, 2019 Accepted 15 July, 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.

Early diagnosis and risk factors of acute hepatitis c in high-risk men who have sex with men on pre-exposure prophylaxis Background: A high incidence of acute HCV (AHCV) infection has been reported among at-risk HIV-negative Men who have Sex with Men (MSM). The optimal strategy for early diagnosis of AHCV in this population is not clearly defined. Methods: In the ANRS IPERGAY PrEP trial among high risk HIV-negative MSM, HCV serology and serum ALT were used for screening at enrollment and during follow-up. Behavioral risk factors were compared at baseline between participants who were diagnosed with AHCV during the study compared to those who did not. In subjects with a positive HCV serology, we used stored sera to perform the following tests at diagnosis and on previous visits: HCV-antibodies rapid tests, plasma HCV viral load and HCV antigen immunoassay. We evaluated the sensitivity of each test for AHCV diagnosis. Results: Among 429 enrolled participants, 14 were diagnosed with AHCV infection, with a median follow-up of 2.1 (IQR: 1.5–2.8) years. AHCV incidence was 1.40 per 100 person-years (95%CI, 0.74–2.39). Patients with AHCV reported a significantly higher number of sexual acts and/or partners, and more frequent recreational drug use at baseline. At the prior visit before AHCV diagnosis (median of 2 months earlier), sensitivities of HCV RNA and HCV antigen tests were respectively 100% and 89%, whereas none of the patients had a positive serology, and only 25% had elevated ALT. Conclusion: HCV antigen and RNA tests were positive within a median of 2 months before the detection of antibodies and ALT elevation. These tests could be considered for HCV screening in high-risk MSM. Correspondence to Julien Gras, Infectious Diseases Department, APHP-Saint Louis Hospital, 1 avenue Claude Vellefaux, Paris, France. Tel: +33 1 42 49 49 91; fax: +33 1 42 49 90 67; e-mail: julien.gras@aphp.fr, Constance Delaugerre, Virology Department, APHP-Saint Louis Hospital, 1 avenue Claude Vellefaux, Paris, France. Tel: +33 1 42 49 94 93; fax: +33 1 42 49 92 00; e-mail: constance.delaugerre@aphp.fr Received 20 February, 2019 Revised 20 June, 2019 Accepted 29 June, 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.

Recently formed age-disparate partnerships are associated with elevated HIV incidence among young women in South Africa Objective: Cross-sectional and cohort studies draw different conclusions on whether age-disparate partnerships increase HIV-acquisition risk for young women. We investigated whether age-disparities were associated with HIV-infection risk early in relationships. This could result in the exclusion of women who seroconverted during high-risk age-disparate partnerships from cohort studies of HIV-incidence – which exclude HIV-positive women – and explain null findings in these studies. Design: Prospective cohort study Methods: We used data on 15–24 year-old, HIV-negative women in heterosexual partnerships (N=830) in KwaZulu-Natal, South Africa. The association between age-disparate partnering (i.e., male partner ≥5 years older) and subsequent HIV-seroconversion was assessed using Cox hazard models. We examined heterogeneity in HIV-acquisition risk by duration of partnership (defined by quartiles) at cohort enrolment. Results: During 1139 person-years (mean: 1.4 years) of follow-up, 54 (6.5%) women seroconverted, a weighted HIV-incidence estimate of 4.41/100 person-years (95% CI 3.30–6.06). HIV-acquisition risk did not differ significantly between women in age-disparate vs. age-similar partnerships (aHR 1.10, 95% CI 0.55–2.21). However, for women in the shortest partnership quartile (<1.09 years) at baseline, risk of HIV-seroconversion was higher for women in age-disparate partnerships (aHR 3.13, 95% CI 1.02–9.65, p = 0.047). HIV-acquisition was not statistically different by partnership type among women in longer partnerships. Conclusions: The association between age-disparate partnerships and HIV-acquisition risk is evident early in young women's relationships. Results provide a potential explanation for null findings in cohort studies, whose research designs may exclude women in such partnerships, and affirms the elevated risk of HIV acquisition for young women in age-disparate relationships. Correspondence to Brendan Maughan-Brown, PhD, Southern Africa Labour and Development Research Unit, University of Cape Town, Private Bag, Rondebosch, 7701, Cape Town, South Africa. Tel: +27-21-650-5695; fax: ++27-21-650-5697; e-mail: brendan.maughanbrown@gmail.com Received 27 March, 2019 Revised 18 July, 2019 Accepted 19 July, 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.

Female genital tract shedding of HIV-1 is rare in women with suppressed HIV-1 in plasma Objective: Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation. Design: We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS). Methods: HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL) (limit of quantitation <20-4000 copies/ml depending on year of collection) for a median of 7.1 years (interquartile range=3.4–9.8, Group 1) or for a median of 1.0 years (IQR = 0.5–1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers. Results: HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668 copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for one year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART. Conclusions: ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation. Correspondence to Julie A.E. Nelson, CB 7295, UNC-CH, Chapel Hill, NC 27599. e-mail: jnelson@med.unc.edu Received 27 March, 2019 Revised 24 June, 2019 Accepted 27 June, 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.

Attrition of HIV-positive children from HIV services in low- and middle-income countries: a systematic review and meta-analysis Introduction: Identification and retention of HIV-positive children in HIV services is essential to ensure optimal health outcomes. This systematic review and meta-analysis examines the magnitude of attrition (loss to follow-up [LTFU] and death) of HIV-positive children from HIV services in low- and middle-income countries (LMICs). Methods: We performed a comprehensive multi-database search of original studies reporting retention/attrition data for HIV-positive children in LMICs through April 2016. Outcomes included LTFU, death, and overall attrition (LTFU + death) at intervals up to 60 months of follow-up. At least two authors determined study eligibility, performed data extraction, and made quality assessments. We used random effects meta-analytic methods to aggregate effect sizes and perform meta-regression analyses. Results: We identified 3,040 unique studies; 91 met eligibility criteria and were included in the analysis. This represents 147,129 HIV-positive children; most were from Africa (83%). LTFU definitions varied widely, with significant variability in outcomes across studies. Most attrition occurred in the first six months of follow-up, increasing to 23% by 36 months. HIV-positive children receiving antiretroviral therapy (ART) had significantly better retention in care than those not on ART. Studies that performed case-finding/tracing for those LTFU had better retention in care up to 24 months of follow-up. Conclusions: These findings underscore the high attrition of children from HIV services in LMICs. Early ART initiation and decentralized patient support services (e.g., tracing for those LTFU) have potential to improve retention in care. Implementation research and resources are urgently needed to improve retention among this vulnerable population. Correspondence to James G. Carlucci, 2525 West End Avenue, Suite 750, Nashville, TN, USA 37203. Tel: +1 615 268 4629; e-mail: james.g.carlucci@vumc.org Received 15 April, 2019 Revised 1 July, 2019 Accepted 10 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Higher soluble CD14 levels are associated with lower visuospatial memory performance in Youth with HIV (YWH) Objective: HIV-associated neurocognitive disorders persist despite early antiretroviral therapy (ART) and optimal viral suppression. We examined the relationship between immunopathogenesis driven by various pathways of immune activation and discrete neurocognitive performance domains in youth with HIV (YWH). Design: Observational cross-sectional study Methods: YWH, ages 20 to 28, enrolled in Adolescent Medicine Trials Network 071/101 were assessed for biomarkers of macrophage, lymphocyte activation and vascular inflammation using ELISA/multiplex assays. Standardized neurocognitive tests were performed, and demographically-adjusted z-scores were combined to form indices of attention, motor, executive function, verbal and visuospatial memory. Cross-sectional analysis of the relationship between 18 plasma inflammatory biomarkers and each neurocognitive domain was performed. Linear regression models were fit for each combination of log-transformed biomarker value and neurocognitive domain score, and were adjusted for demographics, socioeconomic status, substance use, depression, CD4 T cell count, HIV viral load, and ART status. Results: Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% men, 68% African American]. Verbal and visuospatial memory domains were most significantly impaired in the cohort (z = -1.59 and -1.0, respectively). Higher sCD14 was associated with impaired visuospatial memory, which remained robust after adjusting for other biomarkers, demographics, and HIV-associated covariates. Among biomarkers of vascular inflammation, sICAM-1 was negatively associated with verbal memory and attention, while sVCAM-1 was positively associated with executive function and visuospatial memory. Specific neurocognitive domains were not associated with sCD163, LPS, or CCL2 levels. Conclusions: Impaired visuospatial memory in YWH is associated with immune activation, as reflected by higher sCD14. Correspondence to John W. Sleasman, Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Duke University School of Medicine, DUMC Box 2644, Durham, NC 27710. Tel: +919 681 2949; fax: +919 668 3750; e-mail: John.Sleasman@duke.edu Received 10 May, 2019 Revised 16 August, 2019 Accepted 19 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.

Impact of early antiretroviral treatment on sexual behaviour in the INSIGHT Strategic Timing of Anti-Retroviral Treatment (START) Trial Background: Antiretroviral treatment (ART) reduces HIV infectiousness, but the effect of early ART on sexual behaviour is unclear. Methods: We assessed, within the START randomised trial that enrolled HIV-positive adults with CD4>500/mm3, the effect of early (immediate) versus deferred ART on: (i) condomless sex with HIV-serodifferent partners (CLS-D); (ii) all condomless sex (CLS); (iii) HIV transmission-risk-sex (CLS-D-HIV-risk, defined as CLS-D and: not on ART or started ART < 6 months ago or viral load(VL)>200c/mL or no VL in past 6 months), during two year follow-up. Month-12 CLS-D (2010–2014) was the primary outcome. Results: Among 2562 MSM, there was no difference between immediate and deferred arms in CLS-D at month 12 [12.6% versus 13.1%; difference (95% CI): −0.4% (−3.1%, 2.2%), p = 0.75] or month 24, or in CLS. Among 2010 heterosexual men and women, CLS-D at month 12 tended to be higher in the immediate versus deferred arm [10.8% versus 8.3%; difference:2.5% (−0.1%, 5.2%), p = 0.062]; the difference was greater at month 24 [9.3% versus 5.6%; difference:3.7%(1.0%, 6.4%), p = 0.007], at which time CLS was higher in the immediate arm [20.7% versus 15.7%, p = 0.013]. CLS-D-HIV-risk at month 12 was substantially lower in the immediate versus deferred arm for MSM [0.2% versus 11.0%; difference: −10.7% (−12.5%, −8.9%), p < 0.001] and heterosexuals [0.6% versus 7.7%; difference: −7.0% (−8.8%, −5.3%), p < 0.001], due to viral suppression on ART. Conclusions: A strategy of early ART had no effect on condomless sex with HIV-serodifferent partners among MSM, but resulted in modestly higher prevalence among heterosexuals. However, among MSM and heterosexuals, early ART resulted in a substantial reduction in HIV-transmission-risk-sex, to a very low absolute level. Correspondence to Dr Fiona C. Lampe, Institute for Global Health, University College London (UCL), Royal Free Campus, Rowland Hill Street. London, NW3 2PF. E-mail: f.lampe@ucl.ac.uk Received 30 January, 2019 Revised 12 July, 2019 Accepted 16 July, 2019 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 Copyright © 2019 Wolters Kluwer Health, Inc.

Pharmacokinetics of maraviroc in plasma and breastmilk in a treatment-experienced perinatally HIV-1 infected women No abstract available

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.