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Background: Women living with HIV (WLWH) face unique reproductive health (RH) barriers which increase their risks of unmet need for contraception, contraceptive failure, unintended pregnancy, and pregnancy-related morbidity and mortality and may prevent them from achieving their reproductive goals. Patient-centered counseling interventions that support health care workers (HCWs) in providing high-quality RH counseling, tailored to the needs of WLWH, may improve reproductive health outcomes., Methods and Design: We are conducting a non-blinded cluster randomized controlled trial (cRCT) of a digital health intervention for WLWH (clinicaltrials.gov #NCT05285670). We will enroll 3,300 WLWH seeking care in 10 HIV care and treatment centers in Nairobi and Western Kenya. WLWH at intervention sites receive the Mobile WACh Empower intervention, a tablet-based RH decision-support counseling tool administered at baseline and SMS support during two years of follow-up. WLWH at control sites receive the standard of care FP counseling. The decision-support tool is a logic-based tool for family planning (FP) counseling that uses branching logic to guide RH questions based on participants' reproductive life plans, tailoring counseling based on the responses. Follow-up SMSs are based in the Information-Motivation-Behavioral (IMB) Skills model of behavioral change and are tailored to participant characteristics and reproductive needs through separate SMS "tracks". Follow-up visits are scheduled quarterly for 2 years to assess plans for pregnancy, pregnancy prevention, and contraceptive use. The primary outcome, FP discontinuation, will be compared using an intent-to-treat analysis. We will also assess the unmet need for FP, dual method use, viral load suppression at conception and unintended pregnancy., Discussion: The Mobile WACh Empower intervention is innovative as it combines a patient-centered counseling tool to support initial reproductive life decisions with longitudinal SMS for continued RH support and may help provide RH care within the context of provision of HIV care., Competing Interests: The authors have declared that no competing interest exists., (Copyright: © 2024 Ngumbau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose . To summarize the most highly esteemed, peer-reviewed, infectious diseases (ID) pharmacotherapy articles published in 2020. Summary . Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were deemed to have noteworthy contributions to ID pharmacotherapy in 2020, including those on coronavirus disease 2019 (COVID-19) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). To select the most significant articles of 2020, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) to vote on their top 10 articles of general ID and COVID-19 pharmacotherapy and one noteworthy HIV/AIDS publication. A total of 40 articles were nominated by HIDN: 35 articles pertaining to general ID/COVID-19 pharmacotherapy and 5 articles with HIV/AIDS involvement. Of the 247 SIDP members who responded to the survey, 205 and 42 members voted for general ID/COVID-19 pharmacotherapy articles and HIV/AIDS related articles, respectively. The top publications are summarized. Conclusion . In a taxing year of a global pandemic, the abundant and rapid distribution of ID literature has made it challenging for clinicians to stay informed of significant publications across the ID spectrum. This review summarizes significant ID-related publications in 2020 with the goal of aiding clinicians in staying up to date on the most relevant publications in ID pharmacotherapy.

Purpose: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex., Methods: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n = 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "In the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated., Results: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP., Conclusions: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population., (Copyright © 2022. Published by Elsevier Inc.)

Background: Optimized tuberculosis (TB) screening in high burden settings is essential for case finding. We evaluated digital chest X-ray with computer-aided detection (CAD) software (d-CXR) for identifying undiagnosed TB in three primary health clinics in South Africa., Methods: The cross-sectional study consented adults who were sequentially screened for TB using the World Health Organization (WHO) 4 symptom questionnaire and d-CXR. Participants reporting ≥1 TB symptom and/or CAD score ≥60 (suggestive of TB) provided 2 spot sputum for Xpert MTB/RIF Ultra (Xpert Ultra) and liquid culture testing, respectively. TB yield (proportion of screened tested positive) and number needed to test (NNT; no of tests to identify one TB patient) were calculated. Risk factors for microbiologically confirmed or presumed (on radiological grounds) were determined., Results: Among 3041 participants, 45% (1356 of 3041) screened positive on either d-CXR or symptoms. TB yield was 2.3% (71 of 3041) using Xpert Ultra and 2.7% (82 of 3041) using Xpert Ultra plus culture. Modelled TB yield (identified by Xpert Ultra) by screening approach was: 1.9% (59 of 3041) for d-CXR alone, 2.0% (62 of 3041) for symptoms alone and 2.3% (71 of 3041) for both. The NNT was 9.7 for d-CXR, 17.8 for symptoms and 19.1 for d-CXR and/or symptom. Males, those with previous TB, untreated HIV or unknown HIV status, and acute illness were at higher risk of developing TB., Conclusion: d-CXR screening identified a similar yield of undiagnosed TB compared to symptom-based screening, however required fewer diagnostic tests. Due to its objective nature, d-CXR screening may improve case detection in clinics., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: To evaluate the impact of the number of comorbidities on virologic suppression in HIV-positive patients., Methods: This study included patients 18 years or older who were on antiretroviral therapy (ART) with at least 2 visits to an HIV primary care clinic in the past year. The primary outcome was the percentage of patients with an undetectable viral load (a blood HIV RNA level of <20 copies/mL) among groups of patients with 0, 1 or 2, 3 or 4, and 5 comorbidities, respectively. The secondary outcome was the percentage of patients with undetectable viral loads per each comorbidity, as listed above. The study was reviewed by an institutional review board and approved as exempt from full review., Results: Among the 1,144 patients (median age of 52 years, 43% female, 74% Black) included in the study, 80% had an undetectable viral load, and the mean CD4 count was 638 cells/mm3. The majority of patients (48%) had 1 or 2 comorbidities, with only 2 patients having 5 comorbidities. For patients with 0, 1 or 2, 3 or 4, and 5 comorbidities, the percentages of patients with undetectable HIV viral loads were 76%, 81.7%, 87.9%, and 100%, respectively (P = 0.0009 in χ 2 test for trend). When looking at individual comorbidities, corresponding viral suppression rates were as follows: chronic kidney disease, 88.6%; hypertension, 85.8%; type 2 diabetes, 85.7%; clinical atherosclerotic cardiovascular disease, 83.1%; substance abuse, 76%; and psychiatric disorders, 75.2%., Conclusion: Improved viral suppression was seen among HIV-positive patients with an increased number of comorbidities. Patients with psychiatric disorders had the lowest viral suppression rates amongst all of the comorbidity subgroups., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Improving HIV and Hepatitis C Virus (HCV) management among people involved in the criminal justice (CJ) system who use drugs, in particular those with opioid use disorder (OUD), requires effective approaches to screening, linkage, and adherence to integrated prevention and treatment services across correctional and community agencies and providers. This manuscript reviews the literature to explore gaps in HIV, Hepatitis C, and OUD prevention, treatment, and delivery cascades of care for persons involved in the CJ system. Specifically, we compare two models of linkage to prevention and treatment services: Peer/Patient Navigation (PN) wherein the PN links CJ-involved individuals to community-based infectious disease (ID) and substance use prevention and treatment services, and Mobile Health Units (MHU) wherein individuals are linked to a MHU within their community that provides integrated ID and substance use prevention and treatment services. The most notable finding is a gap in the literature, with few to no comparisons of models linking individuals recently released from the CJ system to integrated HIV, Hepatitis C, and OUD prevention and treatment and other harm reduction services. Further, few published studies address the geographical distinctions that affect service implementation and their effects on these substance use, ID and harm reduction care cascades. This manuscript makes specific recommendations to fill this gap through a detailed evaluation of PN and MHU linkage models to co-located and integrated HIV, Hepatitis C, and OUD prevention and treatment services across different communities within the U.S., Competing Interests: Declarations of Interest Springer has received consultation honoraria from Alkermes Inc . Springer has received in-kind study drug donations of Vivitrol from Alkermes Inc and of Sublocade from Indivior pharmaceutical company for NIH-Sponsored research projects., (Published by Elsevier B.V.)

Objective: To molecularly characterise the relationship between Epstein-Barr virus (EBV) genotypes and Pashtun ethnicity., Methods: The cross-sectional study was conducted from November 2018 to December 2019 after approval from the Gomal University, Dera Ismail Khan, Pakistan, and comprised blood samples from transgender sex workers who were seropositive for human immunodeficiency virus-1 and seronegative for human immunodeficiency virus residing in two cities of Khyber Pakhtunkhwa province and Islamabad, the federal capital. Formalin-fixed paraffin-embedded (FFPE). Samples were collected from the partner institute along with the patients data, but without any follow-up from the study subjects which was purely on the basis of physical availability. β-globin gene and EBER-1(EBV encoded small RNA-1) were amplified for qualitative assessment and existence of Epstein-Barr virus. Characterisation of EBNA-2 (EBV Nuclear Antigen-2 was done through nested polymerase chain reaction., Results: Of the 80 subjects, 40(50%) each were seropositive and seronegative individuals. The overall mean age was 28±6.917 years. Among the seropositive group, 38(95%) were homosexual and 2(5%) were heterosexual. Among the seropositive group, 16(40%) had Epstein-Barr virus genotype 1 and 6(15%) had genotype 2, while co-infections were found in 2(5%) subjects. In the seronegative group, 36(90%) subjects had Epstein-Barr virus genotype 1, while there was no case of genotype 2 or co-infection. EBV-2 genotypes with HIV seropositivity showed strong association (p=0.005). Amplification for the EBER-1 gene was done in all the 80(100%) samples., Conclusions: Epstein-Barr virus EBV genotype 1 was found to be the most frequent type, while genotype 2 and co-infections were detected in only seropositive samples.

Background: Children seem relatively protected from serious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease, but little is known about children living in settings with high tuberculosis and human immunodeficiency virus (HIV) burden. This study reflects clinical data on South African children with SARS-CoV-2., Methods: We collected clinical data of children aged <13 years with laboratory-confirmed SARS-CoV-2 presenting to Tygerberg Hospital, Cape Town, between 17 April and 24 July 2020., Results: One hundred fifty-nine children (median age, 48.0 months [interquartile range {IQR}, 12.0-106.0 months]) were included. Hospitalized children (n = 62), with a median age of 13.5 months (IQR, 1.8-43.5 months) were younger than children not admitted (n = 97; median age, 81.0 months [IQR, 34.5-120.5 months]; P < .01.). Thirty-three of 159 (20.8%) children had preexisting medical conditions. Fifty-one of 62 (82.3%) hospitalized children were symptomatic; lower respiratory tract infection was diagnosed in 21 of 51 (41.2%) children, and in 11 of 16 (68.8%) children <3 months of age. Respiratory support was required in 25 of 51 (49.0%) children; 13 of these (52.0%) were <3 months of age. One child was HIV infected and 11 of 51 (21.2%) were HIV exposed but uninfected, and 7 of 51 (13.7%) children had a recent or new diagnosis of tuberculosis., Conclusions: Children <1 year of age hospitalized with SARS-CoV-2 in Cape Town frequently required respiratory support. Access to oxygen may be limited in some low- and middle-income countries, which could potentially drive morbidity and mortality. HIV infection was uncommon but a relationship between HIV exposure, tuberculosis, and SARS-CoV-2 should be explored., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Among persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized., Methods: Patients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels between PHIV with HF and uninfected controls with HF., Results: Among 2578 patients with HF, there were 434 PHIV; 90% were prescribed antiretroviral therapy and 62% were virally suppressed. As compared to controls, PHIV had higher admission (3822 [IQR, 2413-7784] pg/ml vs 5546 [IQR, 3257-8792] pg/ml, respectively; P < .001), higher discharge (1922 [IQR, 1045-4652] pg/ml vs 3372 [IQR, 1553-5452] pg/ml, respectively; P < .001), and lower admission-to-discharge changes in NT-proBNP levels (32 vs 48%, respectively; P = .007). Similar findings were noted after stratifying based on left ventricular ejection fraction (LVEF). In a multivariate analysis, cocaine use, a lower LVEF, a higher NYHA class, a higher viral load (VL), and a lower CD4 count were associated with higher NT-proBNP concentrations. In follow-up, among PHIV, a higher admission NT-proBNP concentration was associated with increased cardiovascular mortality (first tertile, 11.5; second tertile, 20; third tertile, 44%; P < .001). Among PHIV, each doubling of NT-proBNP was associated with a 19% increased risk of death. However, among patients living without HIV, each doubling was associated with a 27% increased risk; this difference was attenuated among PHIV with lower VLs and higher CD4 counts., Conclusions: PHIV with HF had higher admission and discharge NT-proBNP levels, and less change in NT-proBNP concentrations. Among PHIV, VLs and CD4 counts were associated with NT-proBNP concentrations; in follow-up, higher NT-proBNP levels among PHIV were associated with cardiovascular mortality., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Limited data describe patient preferences for the growing number of antiretroviral therapies (ARTs). We quantified preferences for key characteristics of modern ART deemed relevant to shared decision making., Methods: A discrete choice experiment survey elicited preferences for ART characteristics, including dosing (frequency and number of pills), administration characteristics (pill size and meal requirement), most bothersome side effect (from diarrhea, sleep disturbance, headaches, dizziness/difficulty thinking, depression, or jaundice), and most bothersome long-term effect (from increased risk of heart attacks, bone fractures, renal dysfunction, hypercholesterolemia, or hyperglycemia). Between March and August 2017, the discrete choice experiment was fielded to 403 treatment-experienced persons living with human immunodeficiency virus (HIV), enrolled from 2 infectious diseases clinics in the southern United States and a national online panel. Participants completed 16 choice tasks, each comparing 3 treatment options. Preferences were analyzed using mixed and latent class logit models., Results: Most participants were male (68%) and older (interquartile range: 42-58 years), and had substantial treatment experience (interquartile range: 7-21 years). In mixed logit analyses, all attributes were associated with preferences. Side and long-term effects were most important, with evidence of substantial preference heterogeneity. Latent class analysis identified 5 preference classes. For classes 1 (40%), 2 (24%), and 3 (21%), side effects were most important, followed by long-term effects. For class 4 (10%), dosing was most important. Class 5 (4%) was largely indifferent to ART characteristics., Conclusion: Overall, treatment-experienced persons living with HIV valued minimizing side effects and long-term toxicities over dosing and administration characteristics. Preferences varied widely, highlighting the need to elicit individual patient preferences in models of shared antiretroviral decision making., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: High rates of syphilis have been reported worldwide among men who have sex with men (MSM). This study aims to describe the clinical pattern and treatment response of syphilis among human immunodeficiency virus (HIV)-infected MSM in Malaysia., Methods: This is a retrospective study on all HIV-infected MSM with syphilis between 2011 and 2015. Data was collected from case notes in five centres namely Hospital Kuala Lumpur, Hospital Sultanah Bahiyah, Hospital Umum Sarawak, University of Malaya Medical Centre and Hospital Sungai Buloh., Results: A total of 294 HIV seropositive MSM with the median age of 29 years (range 16-66) were confirmed to have syphilis. Nearly half (47.6%) were in the age group of 20-29 years. About a quarter (24.1%) was previously infected with syphilis. Eighty-three patients (28.2%) had other concomitant sexually transmitted infection with genital warts being the most frequently reported (17%). The number of patients with early and late syphilis in our cohort were almost equal. The median pre-treatment non-treponemal antibody titre (VDRL or RPR) for early syphilis (1:64) was significantly higher than for late syphilis (1:8) (p<0.0001). The median CD4 count and the number of patients with CD4 <200/μl in early syphilis were comparable to late syphilis. Nearly four-fifth (78.9%) received benzathine-penicillin only, 5.8% doxycycline, 1.4% Cpenicillin, 1% procaine penicillin, and 12.4% a combination of the above medications. About 44% received treatment and were lost to follow-up. Among those who completed 1 -year follow-up after treatment, 72.3% responded to treatment (serological non-reactive - 18.2%, four-fold drop in titre - 10.9%; serofast - 43.6%), 8.5% failed treatment and 17% had re-infection. Excluding those who were re-infected, lost to follow-up and died, the rates of treatment failure were 12.1% and 8.8% for early and late syphilis respectively (p=0.582)., Conclusion: The most common stage of syphilis among MSM with HIV was latent syphilis. Overall, about 8.5% failed treatment at 1-year follow-up.

Objectives: The aim of this study was to determine the incidence of sudden cardiac death (SCD) among persons living with human immunodeficiency virus infection (PHIV) with heart failure (HF), who were hospitalized for HF, and the risk factors associated with it., Background: HF is associated with an increased risk for SCD. PHIV are at heightened risk for HF., Methods: This was a retrospective study of 2,578 patients hospitalized with HF from a single academic center, of whom 344 were PHIV. The outcome of interest was SCD. Subgroup analyses were performed by strata of viral load (VL) and left ventricular ejection fraction (LVEF) <35%, 35% to 49%, and ≥50%., Results: Of 2,578 patients with HF, 2,149 (86%) did not have implantable cardioverter-defibrillators; of these, there were 344 PHIV and 1,805 uninfected control subjects. Among PHIV with HF, 313 (91%) were prescribed antiretroviral therapy and 64% were virally suppressed. There were 191 SCDs over a median follow-up period of 19 months. Compared with control subjects, PHIV had a 3-fold increase in SCD (21.0% vs. 6.4%; adjusted odds ratio: 3.0; 95% confidence interval: 1.78 to 4.24). Among PHIV, cocaine use, lower LVEF, absence of beta-blocker prescription, and VL were predictors of SCD. The SCD rate among PHIV with undetectable VL was similar to the rate among uninfected subjects. Similar findings were observed by LVEF strata. Among PHIV with HF without conventional indications for an implantable cardioverter-defibrillator, the rate of SCD was 10% per year., Conclusions: PHIV hospitalized with HF are at a markedly increased risk for SCD. SCD risk was increased in patients with lower LVEFs, lower CD4 counts, and higher VL., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We previously reported that pegylated IFN-α2a (Peg-IFN-α2a) added to antiretroviral therapy (ART)-suppressed, HIV-infected subjects resulted in plasma HIV control and integrated HIV DNA decrease. We now evaluated whether innate NK cell activity or PBMC transcriptional profiles were associated with decreases in HIV measures. Human peripheral blood was analyzed prior to Peg-IFN-α2a administration (ART, baseline), after 5 wk of ART+Peg-IFN-α2a, and after 12 wk of Peg-IFN-α2a monotherapy (primary endpoint). After 5 wk of ART+Peg-IFN-α2a, immune subset frequencies were preserved, and induction of IFN-stimulated genes was noted in all subjects except for a subset in which the lack of IFN-stimulated gene induction was associated with increased expression of microRNAs. Viral control during Peg-IFN-α2a monotherapy was associated with 1) higher levels of NK cell activity and IFN-γ-induced protein 10 (IP-10) on ART (preimmunotherapy) and 2) downmodulation of NK cell KIR2DL1 and KIR2DL2/DL3 expression, transcriptional enrichment of expression of genes associated with NK cells in HIV controller subjects, and higher ex vivo IFN-α-induced NK cytotoxicity after 5 wk of ART+Peg-IFN-α2a. Integrated HIV DNA decline after immunotherapy was also associated with gene expression patterns indicative of cell-mediated activation and NK cytotoxicity. Overall, an increase in innate activity and NK cell cytotoxicity were identified as correlates of Peg-IFN-α2a-mediated HIV control., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Background: Persons living with HIV (PLHIV) have an increased risk of heart failure (HF). However, little is known about outcomes among PLHIV with HF. The study aim was to compare HF outcomes among PLHIV with HF versus individuals without HIV with HF., Methods: Our cohort included 2,308 individuals admitted with decompensated HF. We compared baseline characteristics, 30-day HF readmission, and cardiovascular (CV) and all-cause mortality. Within PLHIV, we assessed outcomes stratified between CD4 count and viral load (VL), and tested the association between traditional and HIV-specific parameters with 30-day HF readmission., Results: There were 374 (16%) PLHIV with HF. Among PLHIV, 92% were on antiretroviral therapy and 63% had a VL <200 copies/mL. Groups were similar with respect to age, sex, race/ethnicity, and CV risk factors. In follow-up, PLHIV had increased 30-day HF readmission (49% vs 32%) and CV (26% vs 13.5%) and all-cause mortality rates (38% vs 22%). Among PLHIV, cocaine use, HIV-specific parameters (CD4, VL), and coronary artery disease were predictors of 30-day HF readmission. Specifically, among PLHIV, those with detectable VL had higher 30-day HF readmission and CV mortality, whereas PLHIV with undetectable VL had a similar 30-day HF readmission rate and CV mortality to uninfected controls with HF. Similar outcomes were observed across strata of left ventricular ejection fraction and by CD4., Conclusions: PLHIV with a low CD4 count or detectable VL have an increased 30-day HF readmission rate as well as increased CV and all-cause mortality. In contrast, PLHIV with a higher CD4 count and undetectable VL have similar HF outcomes to uninfected controls., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background People living with HIV ( PHIV ) are at an increased risk for sudden cardiac death, and implantable cardioverter-defibrillators ( ICDs ) prevent SCD . There are no data on the incidence, predictors, and effects of ICD therapies among PHIV . Methods and Results We compared ICD discharge rates between 59 PHIV and 267 uninfected controls. For PHIV , we tested the association of traditional cardiovascular risk factors and HIV -specific parameters with an ICD discharge and then tested whether an ICD discharge among PHIV was associated with cardiovascular mortality or an admission for heart failure. The indication for ICD insertion was similar among groups. Compared with controls, PHIV with an ICD were more likely to have coronary artery disease and to use cocaine. In follow-up, PHIV had a higher ICD discharge rate (39% versus 20%; P=0.001; median follow-up period, 19 months). Among PHIV , cocaine use, coronary artery disease, QRS duration, and higher New York Heart Association class were associated with an ICD discharge. An ICD discharge had a prognostic effect, with a subsequent 1.7-fold increase in heart failure admission and a 2-fold increase in cardiovascular mortality, an effect consistent across racial/ethnic and sex categories. Conclusions ICD discharge rates are higher among PHIV compared with uninfected controls. Among PHIV , cocaine use and New York Heart Association class are associated with increased ICD discharge, and an ICD discharge is associated with a subsequent increase in admission for heart failure and cardiovascular mortality.

Background: Incident heart failure (HF) is increased in persons with human immunodeficiency virus (PHIV). Protease inhibitors (PIs) are associated with adverse cardiac remodeling and vascular events; however, there are no data on the use of PIs in PHIV with HF., Objectives: This study sought to compare characteristics, cardiac structure, and outcomes in PHIV with HF who were receiving PI-based versus non-PI (NPI) therapy., Methods: This was a retrospective single-center study of all 394 antiretroviral therapy-treated PHIV who were hospitalized with HF in 2011, stratified by PI and NPI. The primary outcome was cardiovascular (CV) mortality, and the secondary outcome was 30-day HF readmission rate., Results: Of the 394 PHIV with HF (47% female, mean age 60 ± 9.5 years, CD4 count 292 ± 206 cells/mm 3 ), 145 (37%) were prescribed a PI, whereas 249 (63%) were prescribed NPI regimens. All PI-based antiretroviral therapy contained boosted-dose ritonavir. PHIV who were receiving a PI had higher rates of hyperlipidemia, diabetes mellitus, and coronary artery disease (CAD); higher pulmonary artery systolic pressure (PASP); and lower left ventricular ejection fraction. In follow-up, PI use was associated with increased CV mortality (35% vs. 17%; p < 0.001) and 30-day HF readmission (68% vs. 34%; p < 0.001), effects seen in all HF types. Predictors of CV mortality included PI use, CAD, PASP, and immunosuppression. Overall, PIs were associated with a 2-fold increased risk of CV mortality., Conclusions: PI-based regimens in PHIV with HF are associated with dyslipidemia, diabetes, CAD, a lower left ventricular ejection fraction, and a higher PASP. In follow-up, PHIV with HF who are receiving a PI have increased CV mortality and 30-day HF readmission., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sleep apnea (SA) is common and has prognostic significance among broad groups of patients with heart failure (HF). There are no data characterizing the presence, associations, and prognostic significance of SA among persons living with human immunodeficiency virus (PLHIV) with HF., Methods: We conducted a single-center study of PLHIV with HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] <50%) and analyzed the relationship of SA with 30-day HF hospital readmission rate., Results: Our cohort included 1124 individuals admitted with HFrEF; 15% were PLHIV, and 92% were on antiretroviral therapy. SA was noted in 28% of PLHIV and 26% of uninfected controls. Compared to uninfected controls with HFrEF and SA, PLHIV with HFrEF and SA had a lower body mass index, lower LVEF, a higher pulmonary artery systolic pressure (PASP), were more likely to have obstructive rather than central SA (P < .05 for all). In a multivariable model, PASP, low CD4 count, high viral load (VL), and SA parameters (apnea-hypopnea index, CPAP use and duration) were predictors of 30-day HF readmission rate. Each 1-hour increase in CPAP use was associated with a 14% decreased risk of 30-day HF readmission among PLHIV., Conclusions: Compared to uninfected controls, PLHIV were more likely to have obstructive SA than central SA. Apnea severity, low CD4 count, high VL, and cocaine use were positively associated with 30-day HF hospital readmission rate, whereas CPAP use and increased duration of CPAP use conferred protection.

Objective: International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV-infected individuals and establish local-level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical guidance is provided for such priority-setting processes. Evidence-informed deliberative processes (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant social values with rational decision-making informed by evidence on these values. This study reports on the first-time implementation and evaluation of an EDP in HIV control, organised to support the AIDS Commission in West Java province, Indonesia, in the development of its strategic plan for 2014-2018., Methods: Under the responsibility of the provincial AIDS Commission, an EDP was implemented to select priority interventions using six steps: (i) situational analysis; (ii) formation of a multistakeholder Consultation Panel; (iii) selection of criteria; (iv) identification and assessment of interventions' performance; (v) deliberation; and (vi) selection of funding and implementing institutions. An independent researcher conducted in-depth interviews (n = 21) with panel members to evaluate the process., Results: The Consultation Panel included 23 stakeholders. They identified 50 interventions and these were evaluated against four criteria: impact on the epidemic, stigma reduction, cost-effectiveness and universal coverage. After a deliberative discussion, the Consultation Panel prioritised a combination of several treatment, prevention and mitigation interventions., Conclusion: The EDP improved both stakeholder involvement and the evidence base for the strategic planning process. EDPs fill an important gap which international guidelines and current tools for strategic planning in HIV control leave unaddressed., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: the costs of HIV/AIDS interventions in Indonesia are largely unknown. Knowing these costs is an important input for policy makers in the decision-making of setting priorities among HIV/AIDS interventions. The aim of this analysis is to determine the costs of four HIV/AIDS interventions in Bandung, Indonesia in 2015, to inform the local AIDS commission., Methods: data on utilization and costs of the different interventions were collected in a sexual transmitted infections (STI)-clinic and the KPA, the local HIV/AIDS commission, for the period of January 2015-December 2015. The costs were estimated from a societal perspective, using a micro-costing approach., Results: the total annualized costs for condom distribution, mobile voluntary counselling and testing (VCT), religious based information, communication, and education (IEC) and STI services equalled US$56,926, US$2,985, US$1,963 and US$5,865, respectively., Conclusion: this analysis has provided cost estimates of four different HIV/AIDS interventions in Bandung, Indonesia. Additionally, it has estimated the costs of scaling up these interventions. Together, this provides important information for policy makers vis-à-vis the implementation of these interventions. However, an evaluation of the effectiveness of these interventions is needed to estimate the cost-effectiveness.

Jan Hontelez and colleagues argue that the cost-effectiveness studies of HIV treatment scale-up need to include health system constraints to be more informative.

Background: We report an economic analysis of Human Immunodeficiency Virus (HIV) care and treatment in Indonesia to assess the options and limitations of costs reduction, improving access, and scaling up services., Methods: We calculated the cost of providing HIV care and treatment in a main referral hospital in West Java, Indonesia from 2008 to 2010, differentiated by initiation of treatment at different CD4 cell count levels (0-50, 50-100, 100-150, 150-200, and >200 cells/mm(3)); time of treatment; HIV care and opportunistic infections cost components; and the costs of patients for seeking and undergoing care., Discussion: Before antiretroviral treatment (ART) initiation, costs were dominated by laboratory tests (>65 %), and after initiation, by antiretroviral drugs (≥60 %). Average treatment costs per patient decreased with time on treatment (e.g. from US$580 per patient in the first 6 month to US$473 per patient in months 19-24 for those with CD4 cell counts under 50 cells/mm(3)). Higher CD4 cell counts at initiation resulted in lower laboratory and opportunistic infection treatment costs. Transportation cost dominated the costs of patients for seeking and undergoing care (>40 %)., Conclusions: Costs of providing ART are highest during the early phase of treatment. Costs reductions can potentially be realized by early treatment initiation and applying alternative laboratory tests with caution. Scaling up ART at the community level in certain high prevalence settings may improve early uptake, adherence, and reduce transportation costs.

Background: Indonesia has insufficient resources to adequately respond to the HIV/AIDS epidemic, and thus faces a great challenge in prioritizing interventions. In many countries, such priority setting processes are typically ad hoc and not transparent leading to unfair decisions. Here, we evaluated the priority setting process in HIV/AIDS control in West Java province against the four conditions of the accountability for reasonableness (A4R) framework: relevance, publicity, appeals and revision, and enforcement., Methods: We reviewed government documents and conducted semi-structured qualitative interviews based on the A4R framework with 22 participants of the 5-year HIV/AIDS strategy development for 2008-13 (West Java province) and 2007-11 (Bandung)., Results: We found that criteria for priority setting were used implicitly and that the strategies included a wide range of programmes. Many stakeholders were involved in the process but their contribution could be improved and particularly the public and people living with HIV/AIDS could be better engaged. The use of appeal and publicity mechanisms could be more transparent and formally stated. Public regulations are not yet installed to ensure fair priority setting., Conclusions: To increase fairness in HIV/AIDS priority setting, West Java should make improvements on all four conditions of the A4R framework., (Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.)

Objectives: This study describes the views of various stakeholders on the importance of different criteria for priority setting of HIV/AIDS interventions in Indonesia., Methods: Based on a general list of criteria and a focus group discussion with stakeholders (n = 6), a list was developed of thirty-two criteria that play a role in priority setting in HIV/AIDS control in West-Java province. Criteria were categorized according to the World Health Organization's health system goals and building block frameworks. People living with HIV/AIDS (n = 49), healthcare workers (HCW) (n = 41), the general population (n = 43), and policy makers (n = 22) rated the importance of thirty-two criteria on a 5-point Likert-scale. Thereafter, respondents ranked the highest rated criteria to express more detailed preferences., Results: Stakeholders valued the following criteria as most important for the priority setting of HIV/AIDS interventions: an intervention's impact on the HIV/AIDS epidemic, reduction of stigma, quality of care, effectiveness on individual level, and feasibility in terms of current capacity of the health system (i.e., HCW, product, information, and service requirements), financial sustainability, and acceptance by donors. Overall, stakeholders' preferences for the importance of criteria are similar., Conclusions: Our study design outlines an approach for other settings to identify which criteria are important for priority setting of health interventions. For Indonesia, these study results may be used in priority setting processes for HIV/AIDS control and may contribute to more transparent and systematic allocation of resources.

Unlabelled: Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral set point have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1. A total of 620 individuals with primary HIV-1 infection were screened by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay for HLA class I-restricted, epitope-specific CD8 T cell responses using optimally defined epitopes approximately 2 months after initial presentation. The cohort was predominantly male (97%) and Caucasian (83%) (Fiebig stages II/III [n = 157], IV [n = 64], V [n = 286], and VI [n = 88] and Fiebig stage not determined [n = 25]). Longitudinal viral loads, CD4 count, and time to ART were collected for all patients. We observed strong associations between viral load at baseline (initial viremia) and the established early viral set points (P < 0.0001). Both were significantly associated with HLA class I genotypes (P = 0.0009). While neither the breadth nor the magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag during primary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses--but not others--significantly influenced the time to ART initiation. Individual epitope-specific CD8 T cell responses contribute significantly to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of antiviral function., Importance: Understanding which factors are involved in the control of HIV-1 infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here, using a cohort of over 600 individuals with acute and early HIV-1 infection, we assessed in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV-1 to control of viremia and their impact on the overall course of disease progression., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Introduction: About half a million people in South Africa are deprived of antiretroviral therapy (ART), and there is little systematic knowledge on who they are - e.g. by severity of disease, sex, or socio-economic status (SES). We performed a systematic review to determine the current quantitative evidence-base on equity in utilization of ART among HIV-infected people in South Africa., Method: We conducted a literature search based on the Cochrane guidelines. A study was included if it compared for different groups of HIV infected people (by sex, age, severity of disease, area of living, SES, marital status, ethnicity, religion and/or sexual orientation (i.e. equity criteria)) the number initiating/adhering to ART with the number who did not. We considered ART utilization inequitable for a certain criterion (e.g. sex) if between groups (e.g. men versus women) significant differences were reported in ART initiation/adherence., Results: Twelve studies met the inclusion criteria. For sex, 2 out of 10 studies that investigated this criterion found that men are less likely than women to utilize ART, while the other 8 found no differences. For age, 4 out of 8 studies found inequities and reported less utilization for younger people. For area of living, 3 out of 4 studies showed that those living in rural areas or certain provinces have less access and 2 out of 6 studies looking at SES found that people with lower SES have less access. One study which looked at the marital status found that those who are married are less likely to utilize ART. For severity of disease, 5 out of 6 studies used more than one outcome measure for disease stage and reported within their study contradicting results. One of the studies reported inconclusive findings for ethnicity and no study had looked at religion and sexual orientation., Conclusion: It seems that men, young people, those living in certain provinces or rural areas, people who are unemployed or with a low educational level, and those being unmarried have less access to ART. As studies stem from different contexts and use different methods conclusions should be taken with caution.

Background: Co-infection with tuberculosis (TB) is the leading cause of death in HIV-infected individuals. However, diagnosis of TB, especially in the presence of an HIV co-infection, can be limiting due to the high inaccuracy associated with the use of conventional diagnostic methods. Here we report a gene signature that can identify a tuberculosis infection in patients co-infected with HIV as well as in the absence of HIV., Methods: We analyzed global gene expression data from peripheral blood mononuclear cell (PBMC) samples of patients that were either mono-infected with HIV or co-infected with HIV/TB and used support vector machines to identify a gene signature that can distinguish between the two classes. We then validated our results using publically available gene expression data from patients mono-infected with TB., Results: Our analysis successfully identified a 251-gene signature that accurately distinguishes patients co-infected with HIV/TB from those infected with HIV only, with an overall accuracy of 81.4% (sensitivity = 76.2%, specificity = 86.4%). Furthermore, we show that our 251-gene signature can also accurately distinguish patients with active TB in the absence of an HIV infection from both patients with a latent TB infection and healthy controls (88.9-94.7% accuracy; 69.2-90% sensitivity and 90.3-100% specificity). We also demonstrate that the expression levels of the 251-gene signature diminish as a correlate of the length of TB treatment., Conclusions: A 251-gene signature is described to (a) detect TB in the presence or absence of an HIV co-infection, and (b) assess response to treatment following anti-TB therapy.

Background: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP)., Findings: Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint., Conclusions: The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.

Aim: to evaluate the costs-effectiveness of scaling up community-based VCT in West-Java., Methods: the Asian epidemic model (AEM) and resource needs model (RNM) were used to calculate incremental costs per HIV infection averted and per disability-adjusted life years saved (DALYs). Locally monitored demographic, epidemiological behavior and cost data were used as model input., Results: scaling up community-based VCT in West-Java will reduce the overall population prevalence by 36% in 2030 and costs US$248 per HIV infection averted and US$9.17 per DALY saved. Cost-effectiveness estimation were most sensitive to the impact of VCT on condom use and to the population size of clients of female sex workers (FSWs), but were overall robust. The total costs for scaling up community-based VCT range between US$1.3 and 3.8 million per year and require the number of VCT integrated clinics at public community health centers to increase from 73 in 2010 to 594 in 2030., Conclusion: scaling up community-based VCT seems both an effective and cost-effective intervention. However, in order to prioritize VCT in HIV/AIDS control in West-Java, issues of budget availability and organizational capacity should be addressed.