Decreased growth among antiretroviral drug and HIV exposed uninfected versus unexposed children in Malawi and Uganda Objective: To compare growth among antiretroviral drug and maternal-HIV exposed uninfected (AHEU) versus age-and-sex-matched HIV unexposed uninfected (HUU) children. Design: Prospective cohort of AHEU children identified from the PROMISE trial (NCT01061151: clinicaltrials.gov registry) and age-and-sex-matched HUU controls from child-wellness clinics, enrolled (09/2013–10/2014) in Malawi and Uganda. Methods: Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head-circumference-for-age (HCAZ) z-scores were derived at 12 and 24 months-of-age. Wilcoxon Rank-Sum and Fischer's exact tests were used for unadjusted exposure group comparisons. Generalized-Estimating-Equations models estimated adjusted relative risks (aRR) for poor growth outcomes. Results: Overall, 471 (50.5%) AHEU and 462 (49.5%) HUU children were assessed. Ugandan AHEU compared to HUU children had significantly lower mean LAZ (p < 0.001) and WAZ (p < 0.001) at 12 and 24 months-of-age and HCAZ (p = 0.016) at 24 months, with similar but not significant differences among Malawian AHEU and HUU children. The risk of stunting (more than two standard deviations below the WHO-population LAZ median) was increased among AHEU versus HUU children: aRR = 2.13 (95% confidence interval (CI): 1.36, 3.33), p = 0.001 at 12-months, and aRR = 1.67 (95% CI: 1.16, 2.41), p = 0.006 at 24-months-of-age in Uganda; and aRR = 1.32 (95% CI: 1.10, 1.66), p = 0.018, at 24-months-of-age in Malawi. The risk of HCAZ below WHO median was increased among AHEU versus HUU children at 24-months-of-age, aRR = 1.35 (95% CI: 1.02, 1.79), p = 0.038 in Uganda; and aRR = 1.35 (95% CI: 0.91, 2.02), p = 0.139 in Malawi. Conclusions: Perinatal exposures to maternal-HIV and antiretroviral drugs were associated with lower LAZ (including stunting), WAZ and HCAZ at 24 months-of-age compared HUU children. Correspondence to Jim Aizire, MBCHB, MHS, PhD, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., E7132B. Tel: +10-502-8988; e-mail: jaizire1@jhu.edu Received 5 May, 2019 Revised 31 August, 2019 Accepted 2 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Genetic Clustering Analysis for HIV Infection among Men Who Have Sex with Men in Nigeria: implications for intervention Background: The HIV epidemic continues to grow among MSM in countries across sub-Saharan Africa including Nigeria. To inform prevention efforts, we used a phylogenetic cluster method to characterize HIV genetic clusters and factors associated with cluster formation among MSM living with HIV in Nigeria. Methods: We analyzed HIV-1 pol sequences from 417 MSM living with HIV enrolled in the TRUST/RV368 cohort between 2013 and 2017 in Abuja and Lagos, Nigeria. A genetically linked cluster was defined among participants whose sequences had pairwise genetic distance of 1.5% or less. Binary and multinomial logistic regressions were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with HIV genetic cluster membership and size. Results: Among 417 MSM living with HIV, 153 (36.7%) were genetically linked. Participants with higher viral load (AOR = 1.72 95% CI: 1.04–2.86), no female partners (AOR = 3.66; 95% CI: 1.97–6.08), and self-identified as male sex (compared with self-identified as bigender) (AOR = 3.42; 95% CI: 1.08–10.78) had higher odds of being in a genetic cluster. Compared with unlinked participants, MSM who had high school education (AOR = 23.84; 95% CI: 2.66–213.49), were employed (AOR = 3.41; 95% CI: 1.89–10.70), had bacterial sexually transmitted infections (AOR = 3.98; 95% CI: 0.89–17.22) and were not taking antiretroviral therapy (AOR = 6.61; 95% CI: 2.25–19.37) had higher odds of being in a large cluster (size > 4). Conclusion: Comprehensive HIV prevention packages should include behavioral and biological components, including early diagnosis and treatment of both HIV and bacterial sexually transmitted infections to optimally reduce the risk of HIV transmission and acquisition. Correspondence to Yuruo Li, Department of Epidemiology, University of Maryland School of Public Health, 6100 Westchester Park Drive, Apt 520, College Park, MD 20740, USA. Tel: +1 404 539 6249; e-mail: yuruo.li12@gmail.com Received 6 June, 2019 Revised 24 September, 2019 Accepted 25 September, 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.

Comparison of guidelines for HIV viral load monitoring among pregnant and breastfeeding women in sub-Saharan Africa: a simulation study Background: Intensified viral load (VL) monitoring for pregnant and breastfeeding women has been proposed to help address concerns around antiretroviral therapy (ART) adherence, viraemia and transmission risk, but there have been no systematic evaluations of existing policies. Methods: We used an individual Monte Carlo simulation to describe longitudinal ART adherence and VL from conception until two years postpartum. We applied national and international guidelines for VL monitoring to the simulated data. We compared guidelines on the percentage of women receiving VL monitoring and the percentage of women monitored at the time of elevated VL. Results: Coverage of VL monitoring in pregnancy and breastfeeding varied markedly, with between 14–100% of women monitored antenatally and 38–98% monitored during breastfeeding. Specific recommendations for testing at either a fixed gestation or a short, fixed period after ART initiation achieved >95% testing in pregnancy but this was much lower (14–83%) among guidelines with no special stipulations. By the end of breastfeeding, only a small proportion of simulated episodes of elevated VL > 1000 copies/mL were successfully detected by monitoring (range, 20–50%). Discussion: While further research is needed to understand optimal VL frequency and timing in this population, these results suggest that current policies yield suboptimal detection of elevated VL in pregnant and breastfeeding women. Correspondence to Maia Lesosky, Division of Epidemiology & Biostatistics, School of Public Health & Family Medicine, University of Cape Town Faculty of Health Sciences, Anzio Road, Observatory 7925, South Africa. Tel: +27(0)216504532; e-mail: lesosky@gmail.com Received 17 June, 2019 Revised 30 August, 2019 Accepted 13 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

All-cause mortality after ART initiation in HIV-positive women from Europe, Sub-Saharan Africa and the Americas Background: Women account for over half of persons living with HIV/AIDS globally. We examined geographic variation in all-cause mortality after antiretroviral therapy (ART) for women living with HIV (WLWH) worldwide. Methods: We pooled data from WLWH at least 18 years initiating ART 2000–2014 within COHERE (Europe) and IeDEA regions (East Africa, West Africa, South Africa, North America, Latin America/Caribbean). Mortality rates were calculated at 0–3, 3–6, 6–12, 12–24 and 24–48 months after ART, and mortality rate ratios were compared with European rates with piecewise exponential parametric survival models based on Poisson regression. Findings: Nineteen thousand, one hundred and seventy-five WLWH (16% Europe, 47% East Africa, 13% West Africa, 19% South Africa, 1% South America, 3% North America and 2% Central America/Caribbean) were included. The highest death rates occurred 0–3 months after ART [1.51 (95% CI 1.25–1.82) per 100 person-years in Europe, 12.45 (11.30–13.73), 14.03 (13.12–15.02) and 9.44 (8.80–10.11) in East, West and South Africa, and 1.53 (0.97–2.43), 7.83 (5.44–11.27) and 17.02 (14.62–19.81) in North, South America and Central America/Caribbean, respectively] and declined thereafter. Mortality in Europe was the lowest, with regional differences greatest in the first 3 months and smaller at longer ART durations [adjusted rate ratios 24–48 months after ART: 3.63 (95% CI 3.04–4.33), 5.61 (4.84–6.51) and 3.47 (2.97–4.06) for East, West and South Africa; 2.86 (2.26–3.62), 2.42 (1.65–3.55) and 2.50 (1.92–3.26) for North, South America and Central America/Caribbean, respectively]. Conclusion: Global variations in short-term and long-term mortality among WLWH initiating ART may inform context-specific interventions. Correspondence to Julia del Amo, National Plan on HIV/AIDS/STIs, Ministry of Health, Consumer Affairs and Social Well being, Madrid, Spain. E-mail: jamo@mscbs.es Received 17 June, 2019 Revised 3 September, 2019 Accepted 13 September, 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.

Development and Validation of the First Point-of-Care Assay to Objectively Monitor Adherence to HIV Treatment and Prevention in Real-Time in Routine Settings Objective: HIV prevention and treatment studies demonstrate that pharmacologic adherence metrics are more accurate than self-report. Currently-available metrics use liquid-chromatography/tandem-mass-spectrometry (LC-MS/MS), which is expensive and laboratory-based. We developed a specific and sensitive antibody against tenofovir, the backbone of treatment and prevention, but conversion to a lateral flow assay (LFA) –analogous to a urine pregnancy test- is required for point-of-care testing. We describe the development of the first LFA to measure antiretroviral adherence in real-time. Methods: Previous work in a directly-observed therapy study of providing tenofovir-disoproxil fumarate (TDF) to HIV-noninfected volunteers at various simulated adherence patterns defined the appropriate cut-off for the LFA (1500ng tenofovir/ml urine). We developed the LFA using a sample pad for urine; a conjugate pad coated with TFV-specific antibodies conjugated to colloidal gold nanoparticles; a nitrocellulose membrane striped with tenofovir-antigen (test line) and a control line; with an absorbent pad to draw urine across the reaction membrane. Results: We tested 300 urine samples collected from the directly-observed therapy study by this LFA and the gold-standard method of LC-MS/MS. The LFA demonstrated 97% specificity (95% CI: 93% to 99%) and 99% sensitivity (94% to 100%) compared to LC-MS/MS. The LFA accurately classified 98% of patients who took a dose within 24 hours as adherent. Conclusion: We describe the development and validation of the first point-of-care assay to measure short-term adherence to HIV prevention and treatment in routine settings. The assay is low-cost, easy-to-perform and measures the breakdown product (tenofovir) of both TDF and tenofovir alafenamide (TAF). This assay has the potential to improve HIV and PrEP outcomes worldwide by triggering differentiated service delivery with further study merited. Correspondence to Monica Gandhi,MD, MPH, Professor of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, 995 Potrero Avenue, 4th floor, Room 423D, San Francisco, CA 94110. Tel: +415 476 4082 ext 138; fax: +415 476 9653; e-mail: monica.gandhi@ucsf.edu Received 19 July, 2019 Revised 28 August, 2019 Accepted 29 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

CD4 count stratification to guide tuberculosis preventive therapy for people living with HIV Objectives: In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4≤350 cells/μL, but only for those with a positive tuberculin skin test (TST) if CD4> 350 cells/μL. We determined the potential effectiveness of CD4-based guidelines for TB testing and preventive therapy. Design: Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT). Methods: We analyzed data from 4,114 newly-registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4, TST, IPT, and antiretroviral therapy (ART) categories. Results: Initial CD4 count was ≤350 in 2,138 (52%) and > 350 in 1,976 (48%) patients. TST was performed for 2,922 (71%), of whom 657 (16%) were TST-positive (278 [13%] CD4≤350 vs. 379 [19%] CD4> 350). A total of 619 (15%) received IPT and 2,806 (68%) received ART. For patients with CD4≤350 who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100pys. For patients with CD4> 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100pys and 1.49/100pys for TST-negatives, and 1.05/100pys and 1.64/100pys for TST-unknowns. Conclusions: TB incidence was high among all patients who did not receive IPT, including those with CD4> 350 and negative or unknown TST results. TB preventive therapy should be provided to all PLWH in medium burden settings, regardless of CD4 count and TST status. Correspondence to Jonathan Golub, PhD, Johns Hopkins University Center for Tuberculosis Research, 1550 Orleans Street, Cancer Research Building-2, Baltimore, MD 21287. Tel: +43-287-2969; e-mail: jgolub@jhmi.edu Received 13 August, 2019 Revised 3 September, 2019 Accepted 13 September, 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.

Immune checkpoint inhibitors in people living with HIV: what about anti-HIV effects? Immune checkpoint inhibitors (ICPi) have shown major therapeutic successes when used in various cancers. In the HIV field a double benefit of such ICPi should result from their dual ability to restore in-vitro HIV-specific CD8+ T-cell functions and to enhance HIV production from reservoir cells, thus fulfilling the goals of the ‘shock and kill’ concept proposed as an HIV cure therapeutic strategy. We conducted a systematic review to identify studies reporting the tolerance profile of ICPi and their effects on HIV plasma loads (pVL), CD4+ count, HIV reservoirs (cell-associated HIV-DNA) and/or HIV-specific CD8+ T in PLWH. Thirty-four articles were included for a total 176 participants. 12.1% participants experienced severe adverse events and 49.4% nonsevere adverse events. pVL remained stable in 91.9% participant, showed increases in 5.8% participant, and decreases in 2.3%. CD4+ count remained stable in 60.7% participants, showed increases in 24.6%, and decreases in 14.7%. Regarding ICPi effects on HIV-DNA and HIV-specific immunity, we identified three distinct profiles: profile I, transient pVL increases followed by a boost in HIV-specific CD8+ T cells concomitant to a decrease in HIV-DNA, reported in one participant. Profile II: increase in HIV-specific CD8+ T cells without changes in pVL or HIV-DNA, reported in three participants. III: no effect, reported in five participants. In conclusion, the clinical, virological and immunological safety profiles of ICPi reported in about 200 PLWH appear to be favorable but their still modest results in terms of HIV cure strategy. Correspondence to Jean-Philippe Spano, MD, PhD, Hopital Universitaire, Pitie Salpetriere, F-75013 Paris, France. Tel: +33 1 42 16 04 72; fax: +33 1 42 16 04 69; e-mail: jean-philippe.spano@aphp.fr Received 13 June, 2019 Revised 6 September, 2019 Accepted 15 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Cytomegalovirus (CMV)-Vectored vaccines for HIV and other pathogens No abstract available

Polypharmacy and evaluation of anticholinergic risk in a cohort of elderly people living with HIV As a consequence of ageing, the number of prescribed medications for people living with HIV (PLWH) is increasing. Concomitant use of different drugs and their potential interactions may increase anticholinergic exposure and escalate the risk for side effects. We conducted an analysis in our cohort of PLWH over 50 years of age to evaluate the overall anticholinergic risk, as it is useful to identify, prevent, and manage increased side effect risks. Correspondence to Dr Maria Mazzitelli, MD, Magna Graecia University, Catanzaro (Italy), Chelsea and Westminster Hospital, London (UK). E-mail: m.mazzitelli88@gmail.com Received 26 July, 2019 Revised 22 August, 2019 Accepted 2 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Association of CR2 genotypes with the acquisition of HIV infection in a trial of recombinant glycoprotein 120 Vaccine Objectives: CR2 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CR2 genetic variants are associated with susceptibility to systemic lupus erythematosus as well as to HIV-1 infection. Additionally, CR2 function can be subverted by HIV-1 for an efficient entry into target cells; in a process known as antibody-dependent enhancement of viral infection. We sought to determine the association between CR2 gene variants with HIV-1 acquisition after vaccination with recombinant gp120 protein (Vax004 clinical trial). Design and Methods: This is a retrospective cross-sectional study, comprising male subjects of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for 3 SNPs in the CR2 gene region. Results: An interaction was observed between the baseline sexual behaviour and the SNP rs3813946 for higher risk of infection in vacinees (interaction term p = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in subjects with low behavioral risk OR [95%CI]: 5.5 [1.4–21.7], p = 0.006 but not vaccinees with high behavioral risk or subjects given placebo (p = 0.7). Moreover, CR2 genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low risk subjects (Hazard odds ratio [95%CI]: 3.3 [1.6–7.0], p = 0.001). Conclusions: This study suggests that CR2 may play a role in HIV-1 acquisition after vaccination with rgp120 proteins. Correspondence to Antonio Caruz, PhD. Immunogenetics Unit, Universidad de Jaén, Campus Las Lagunillas SN, 23071, Jaén, Spain. Tel: +34 953212706; fax: +34 953211875; e-mail: caruz@ujaen.es Received 2 August, 2019 Revised 29 August, 2019 Accepted 16 September, 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.