Potential health gains among key populations in West and Central Africa through savings from lower-cost HIV treatment Objective: Prices of antiretroviral (ARV) drugs in lower-income countries have decreased substantially over the past two decades, helping facilitate greatly expanded access to antiretroviral therapy (ART). However, ART coverage in many parts of the world remains low. We investigate the extent of epidemiological benefits that might be expected if ARV drug prices declined further. Design: A modeling study using data from seven countries in West and Central Africa (Cameroon, Democratic Republic of the Congo, Côte d’Ivoire, Niger, Nigeria, Senegal, and Togo). Methods: We investigated how the timing of ARV cost reductions could affect the impact and compared three different possible investment strategies: reinvesting in ART, reinvesting in the HIV response according to historical allocations, and reinvesting with the aim of minimizing HIV incidence and mortality. Results: If ARV prices fell by 37% relative to 2018 levels (i.e., following continued trend declines), we calculate ART unit costs could decrease by ∼20% (holding other cost components constant). If this could be achieved by 2020 and the savings were reinvested into ART, we estimate that an additional 8% of HIV infections and 11% of HIV-related deaths could be averted over 2020–2030 across the 7 countries. Slightly greater gains could be attained if funds were reinvested in ART in combination with primary prevention. Delays in the year of introduction of ARV price reductions would reduce the impact by about 1% per year. Conclusion: ARV price reductions could free up funds that – if strategically invested – would help countries move closer toward the elimination of HIV. Correspondence to Robyn M. Stuart, Universitetsparken 5, København Ø, 2300, Denmark. Tel: +45 2878 5222; e-mail: robyn@math.ku.dk Received 19 March, 2019 Revised 2 October, 2019 Accepted 7 October, 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.

Association between quality of care indicators for HIV infection and healthcare resource utilization and costs Objectives: Multiple care quality indicators for HIV infection exist but few studies examine their impact on health outcomes. This study assessed, which HIV quality indicators were associated with healthcare resource utilization and costs. Design: Retrospective analysis of Texas Medicaid claims data (01 January 2012 to 31 September 2016). Methods: Included patients had at least two HIV-related medical claims during the identification period (01 July 2012 to 31 August 2014) (index = date of first HIV claim), were 18–62 years at index, and were continuously enrolled in the 6-month pre-index and 1-year post-index periods. Dependent variables included emergency department (ED) visits, inpatient hospitalizations, prescription count, and all-cause healthcare costs. Independent variables included CD4+ cell count monitoring, syphilis, chlamydia, gonorrhea, hepatitis B, hepatitis C, and tuberculosis screenings, influenza and pneumococcal vaccinations, retention in care, and HAART initiation. Covariates included age, chronic hepatitis C virus infection, AIDS diagnosis, sex, and baseline healthcare cost. The study objective was addressed using generalized linear modeling. Results: CD4+ cell count monitoring and HAART initiation were significantly associated with reduced emergency department visits (P < 0.0001 for each). Influenza vaccination was significantly associated with reduced inpatient hospitalization (P < 0.0001). CD4+ cell count monitoring (P < 0.0001), TB screening (P = 0.0006), influenza vaccination (P < 0.0001), and HAART initiation (P < 0.0001) were significantly associated with increase prescription claims. CD4+ cell count monitoring, TB screening, and HAART initiation (P < 0.0001 for each) were significantly associated with all-cause healthcare costs. Conclusion: HAART may reduce use of emergency care services as early as 1 year following initiation. Correspondence to Jamie C. Barner, Health Outcomes Division, The University of Texas at Austin College of Pharmacy, 2409 University Avenue MC A1930, Austin, TX 78712, USA. E-mail: jbarner@austin.utexas.edu Received 10 May, 2019 Revised 27 September, 2019 Accepted 7 October, 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.

Lifetime alcohol use among persons living with hiv is associated with frailty Background: The average lifespan of persons living with HIV (PLWH) on antiretroviral therapy approximates the general population. However, PLWH are susceptible to early aging and frailty. Behaviors such as alcohol consumption may contribute to frailty among PLWH. Objective: To determine the relationships between recent and lifetime alcohol use and frailty among PLWH. Design: Cross-sectional, prospective cohort study of in-care PLWH (n = 365) participating in the New Orleans Alcohol Use in HIV Study. Methods: Recent alcohol exposure was measured by the 30-day alcohol timeline follow-back (TLFB) assessment and by whole-blood-spot phosphatidylethanol (PEth) quantitation. Lifetime alcohol exposure (LAE) was estimated by a modified lifetime drinking history instrument. Frailty was assessed by a 58-item deficit index (DI58) and the phenotypic frailty index (PFI). The Veterans Aging Cohort Study Risk Index 2.0 was calculated. Results: Using generalized linear regression, LAE was positively associated with the DI58 [95%CI:(0.001,0.006)] and PFI severity [95%CI:(0.004,0.023)] after adjustment for age and other factors. Conversely, recent alcohol exposure was negatively associated with the DI58 [TLFB 95% CI: (−0.126, −0.034), PEth: (−0.163, −0.058)] and PFI severity [TLFB 95% CI: (−0.404, −0.015), PEth: (−0.406, 0.034)]. The VACS was not associated with alcohol use. Median per-decade alcohol exposure peaked in the second decade and tapered with aging thereafter. Increasing LAE and decreasing TLFB were co-associated with a specific subset of health deficits. Conclusion: Lifetime alcohol use is positively associated with frailty among PLWH. Specific health deficits may discourage alcohol consumption in some PLWH. Correspondence to David A. Welsh, MD, New Orleans, United States. Tel: +504 568 4634; fax: +504 568 4295; e-mail: dwelsh@lsuhsc.edu Received 15 May, 2019 Revised 13 October, 2019 Accepted 14 October, 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 effects of Lactobacillus casei Shirota in treated HIV-infected patients with poor CD4+ T cell recovery: a randomized trial Background: HIV infection leads to depletion of intestinal CD4+ T cells, mucosal barrier dysfunction, increased gut permeability and microbial translocation even among patients on suppressive ART. Previous studies suggest probiotics may help restore intestinal function. Methods: In this double-blind, placebo-controlled pilot study, we enrolled HIV-infected patients on suppressive ART with poor CD4+ recovery to address the effect of daily oral use of Lactobacillus casei Shirota (LcS) on CD4+ T cell count and CD4/CD8 ratio at 6 and 12 weeks after treatment initiation; immune activation and intestinal microbiome composition were addressed as secondary outcomes. Results: From Jan/2015 to Jul/2016, 48 patients were randomized (1:1) to active intervention or placebo. Groups had comparable demographic and clinical characteristics; only CD4+ T cell nadir was statistically different between groups. All participants were virologically-suppressed under ART. At week 6, the increment in CD4+ T cell count was 17 cells/mm3 (interquartile range [IQR] −33 to 74) in the active intervention arm and 4 cells/mm3 (IQR −43 to 51) in the placebo arm (p = 0.291); at week 12, the change in CD4+ T cell count was 8 cells/mm3 (IQR −30 to 70) in the active arm and 10 cells/mm3 (IQR −50 to 33) among participants allocated to placebo (p = 0.495). Median change in CD4/CD8 ratio at week 6 compared to baseline was 0 (IQR −0.04 to 0.05) in the active intervention arm and −0.01 in the placebo arm (IQR −0.06 to 0.03; p = 0.671). At week 12, the change in CD4/CD8 ratio was higher in the active product group compared to placebo (respectively 0.07 and 0.01), but this difference failed to reach statistical significance (p = 0.171). We found no significant effects of LcS on immune activation markers, CD4+ and CD8+ subpopulations, sCD14 levels or NK cells at week 12. Finally, we found no statistically significant differences between groups in the change of enteric microbiome at week 12. Conclusions: In this pilot study, we found no statistically significant effect of LcS probiotic on CD4+ T cell counts, CD4/CD8 ratio, immune activation or intestinal microbiome among HIV-infected patients on suppressive ART with poor CD4+ recovery. Correspondence to Esper Georges Kallas, MD, PhD, University of Sao Paulo, São Paulo, SP BRAZIL. E-mail: esper.kallas@usp.br Received 23 May, 2019 Revised 29 September, 2019 Accepted 5 October, 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.

Diverging trends in incidence of HIV versus other sexually transmitted infections in HIV-negative men who have sex with men (MSM) in Amsterdam Objectives: We investigated changes in incidence rates of HIV and sexually transmitted infections (STI) and trends in sexual behavior in MSM from 2009-2017. Design: Open prospective cohort study. Methods: HIV-negative MSM enrolled in the Amsterdam Cohort Studies were included. Participants semiannually completed a questionnaire on sexual behavior and were tested for HIV-1, syphilis, and urethral, anal and pharyngeal chlamydia and gonorrhea. Time trends in incidence rates were analyzed using exponential survival models. Results: During follow-up, 42 of 905 MSM acquired HIV. The HIV incidence rate was 1.9/100 person-years (PY) (95%-confidence interval (CI) 1.0–3.7) in 2009 and decreased to 0.5/100 PY (95%-CI 0.2–1.4) in 2017 (p = 0.03). The largest decrease was observed in participants aged ≥35 years (p = 0.005), while the trend remained stable in 18–34 year olds (p = 0.4). The incidence rate for any bacterial STI was 16.8/100 PY (95%-CI 13.4–21.0) in 2010, and increased to 33.1/100 PY (95%-CI 29.0–37.9) in 2017 (p < 0.001). Between 2009–2017, the percentage reporting condomless anal sex (CAS) with casual partners increased from 26.9% to 39.4% (p < 0.001), and the mean number of casual partners from 8 (95%-CI 8–8) to 11 (95%-CI 10–11) (p = 0.05). CAS with steady partner(s) remained stable over time (p = 0.5). Conclusions: Among MSM in Amsterdam, incidence rates of HIV versus other STI show diverging trends. The increase in STI incidence coincides with a decrease in condom use with casual partners. The decrease in HIV incidence, despite increased sexual risk behavior, suggests that other HIV prevention methods have been successful in reducing HIV transmission among MSM. Correspondence to Ward Peter Hubertus van Bilsen, MD, Public Health Service of Amsterdam, Department of Infectious Diseases and Research, Nieuwe Achtergracht 100, 1018 WT Amsterdam. Tel: ++31205553815; e-mail: wvbilsen@ggd.amsterdam.nl Received 13 June, 2019 Revised 27 September, 2019 Accepted 7 October, 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.

Weight gain in people living with HIV switched to dual therapy: changes in body fat mass Changes in weight and body composition were assessed in long-term suppressed HIV-infected patients switching to dolutegravir/rilpivirine (n = 37), and compared with similar patients switching to darunavir/lamivudine (n = 17). At month 12, weight significantly increased with dolutegravir/rilpivirine (1.8 kg, IQR −1.2 to 4.1; 2.5%; P = 0.03). A follow-up DXA (median, 16 months) showed similar increases in trunk (7.8%), arms (5.6%), and legs (6.2%) fat mass, without changes in lean mass. Despite lower weight gain (0.70 kg, IQR −0.8 to 4.0, P = 0.28), fat mass increase was similar in the darunavir/lamivudine group. Baseline fat mass and CD4 counts were the only factors explaining fat mass gain. Correspondence to Pilar Vizcarra, MD, Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Cra. Colmenar km 9.1, 28034 Madrid, Spain. Tel: +34 913368672; fax: +34 913369100; e-mail: pilar1vizcarra@gmail.com Received 16 June, 2019 Revised 25 September, 2019 Accepted 5 October, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Global status of Toxoplasma gondii infection and associated risk factors in people living with HIV: A systematic review and meta-analysis Objective: Toxoplasma infection remains as the most common cause of focal brain lesions among people living with HIV (PLHIV) despite the decline in opportunistic infections with the introduction of antiretroviral treatment. This study was conducted to provide a summary of evidence about the seroprevalence of Toxoplasma gondii and prevalence of active T. gondii infection and associated risk factors among PLHIV. Design: PRISMA guidelines were followed. Scopus, PubMed, Science Direct, and EMBASE were searched from 1997 to July 2018. All peer-reviewed original research articles describing T. gondii infection among PLHIV with different diagnostic methods were included. Methods: Incoherence and heterogeneity between studies were quantified by I2 index and Cochran's Q test. Publication and population bias were assessed with funnel plots and Egger's regression asymmetry test. All statistical analyses were performed using StatsDirect. Results: A total of 111 studies from 37 countries assessing 66,139 blood samples were included in this study. The pooled prevalence of T. gondii infection among PLHIV was 3.24% by IgM and 26.22% by molecular methods using the random-effects model. Pooled seroprevalence of T. gondii by IgG was 44.22%. There was a relationship between Toxoplasma prevalence and gender, raw meat consumption, contact with cat and knowledge about toxoplasmosis. Conclusion: High Toxoplasma seroprevalence among PLHIV observed in this study emphasizes the need for implementing screening and prophylaxis tailored to the local context. Owing to the serious and significant clinical manifestations of the parasite in case of reactivation, early identification of seropositivity for initiating prophylaxis among those with a CD4 count of <200cells/mL is recommended. Correspondence to Ehsan Ahmadpour, Ph.D, Department of Parasitology and Mycology, Tabriz university of Medical Sciences, Tabriz, PO Box: 14155-6446, Iran. Tel: +98 413 5428595; fax: +98 413 337 3745; e-mail: ehsanahmadpour@gmail.com,ahmadpoure@tbzmed.ac.ir Received 2 July, 2019 Revised 6 October, 2019 Accepted 14 October, 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 HIV and antiretroviral drug exposure on lung growth and function over 2 years in an African Birth Cohort Objective: To assess the impact of HIV and antiretroviral (ARV) exposure without infection on lung growth and function over the first 2 years of life. Design: Prospective observational study of an African birth cohort, Drakenstein Child Health Study (DCHS). Method: Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received ARV therapy (ART) as per local guidelines. The association between HIV and ARV exposure with lung function was assessed using mixed effects modelling. Results: Of 1143 infants born, 2 HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks (190 [21%] were HIV-exposed uninfected [HEU]); 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume (TV) compared to HIV unexposed infants (1.13 mL, CI: 0.02 to 2.23, p = 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, CI 0.00 to 0.34, p = 0.046). First-line ART initiated during pregnancy was associated with lower infant TV at 6 weeks compared to those who initiated ART before pregnancy (−2.7 mL, −5.31 to −0.10, p = 0.042), and low maternal CD4 cell counts associated with lower infant tidal over 2 years (−11.1 mL, −18.58 to 3.58, p = 0.004). Conclusion: HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. This data highlights the importance of ongoing surveillance of respiratory health in HEU children. Correspondence to Diane M. Gray, Ph.D, M.D., University of Cape Town, Cape Town, South Africa. E-mail: diane.gray@uct.ac.za Received 13 August, 2019 Revised 25 October, 2019 Accepted 26 October, 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). 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.

HIV viral load algorithm, what are the needs in the field? No abstract available

Altered monocyte phenotype and dysregulated innate cytokine responses among people living with HIV and opioid-use disorder Background: Opioid-use disorders (OUD) and hepatitis C or B co-infection (HEP) are common among people living with HIV (PLHIV). The impact of OUD on innate and adaptive immunity among PLHIV with and without HEP is unknown. Objectives: To investigate the impact of OUD on monocyte and T-cell phenotypes, cytokine responses to lipopolysaccharide (LPS) and phytohemagglutinin (PHA), and plasma inflammatory markers, among PLHIV with and without HEP. Methods: Cross-sectional study enrolling PLHIV receiving ART, with and without OUD. Flow cytometry determined monocyte and T-cell phenotypes; LPS and PHA-induced cytokine production was assessed following LPS and PHA stimulation by multiplex cytokine array; plasma IL-6, soluble CD163, and soluble CD14+ were measured by ELISA. Results: Twenty-two PLHIV with OUD and 37 PLHIV without OUD were included. PLHIV with OUD exhibited higher frequencies of intermediate (CD14++CD16+) and nonclassical (CD14dimCD16+) monocytes when compared with PLHIV without OUD (P = 0.0025; P = 0.0001, respectively), regardless of HEP co-infection. Soluble CD163 and monocyte cell surface CD163 expression was increased among PLHIV with OUD and HEP, specifically. Regardless of HEP co-infection, PLHIV with OUD exhibited reduced production of IL-10, IL-8, IL-6, IL-1alpha, and TNF-alpha in response to LPS when compared with PLHIV without OUD; PHA-induced production of IL-10, IL-1alpha, IL-1beta, IL-6, and TNF-alpha were also reduced among individuals with OUD. Conclusion: OUD among PLHIV are associated with altered monocyte phenotypes and a dysregulated innate cytokine response. Defining underlying mechanisms of opioid-associated innate immune dysregulation among PLHIV should be prioritized to identify optimal OUD treatment strategies. Correspondence to Christina L. Lancioni, MD, Department of Pediatrics, Oregon Health & Science University, 707 SW Gaines Street, CDRC-P, Portland, OR 97239, USA. Tel: +1 503 418 1484; fax: +1 503 494 1542; e-mail: Lancioni@ohsu.edu Received 7 June, 2019 Revised 13 September, 2019 Accepted 3 October, 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). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 Wolters Kluwer Health, Inc.