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In first-line antiretroviral therapy (ART) for human immunodeficiency virus (HIV) treatment, some subgroups of patients may respond better to an efavirenz-based regimen than an integrase strand transfer inhibitor (InSTI)-based regimen, or vice versa, due to patient characteristics modifying treatment effects. Using data based on nearly 16,000 patients from the North American AIDS Cohort Collaboration on Research and Design from 2009-2016, statistical methods for precision medicine were employed to estimate an optimal treatment rule that minimizes the 5-year risk of the composite outcome of acquired immune deficiency syndrome (AIDS)-defining illnesses, serious non-AIDS events, and all-cause mortality. The treatment rules considered were functions that recommend either an efavirenz- or InSTI-based regimen conditional on baseline patient characteristics such as demographic information, laboratory results, and health history. The estimated 5-year risk under the estimated optimal treatment rule was 10.0% (95% confidence interval (CI): 8.6, 11.3), corresponding to an absolute risk reduction of 2.3% (95% CI: 0.9, 3.8) when compared with recommending an efavirenz-based regimen for all patients and 2.6% (95% CI: 1.0, 4.2) when compared with recommending an InSTI-based regimen for all. Tailoring ART to individual patient characteristics may reduce 5-year risk of the composite outcome compared with assigning all patients the same drug regimen., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV)., Methods: We included adults from the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen containing either InSTI or EFV between 2009 and 2016. We estimated differences in the proportion virologically suppressed up to 7 years of follow-up in observational intention-to-treat and per-protocol analyses., Results: Of 15 318 participants, 5519 (36%) initiated an InSTI-based regimen and 9799 (64%) initiated the EFV-based regimen. In observational intention-to-treat analysis, 81.3% of patients in the InSTI group and 67.3% in the EFV group experienced virologic suppression at 3 months after ART initiation, corresponding to a difference of 14.0% (95% CI 12.4-15.6). At 1 year after ART initiation, the proportion virologically suppressed was 89.5% in the InSTI group and 90.2% in the EFV group, corresponding to a difference of -0.7% (95% CI -2.1 to 0.8). At 7 years, the proportion virologically suppressed was 94.5% in the InSTI group and 92.5% in the EFV group, corresponding to a difference of 2.0% (95% CI -7.3 to 11.3). The observational per-protocol results were similar to intention-to-treat analyses., Conclusions: Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes., Methods: We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death., Results: Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, -2.7% to 3.3%) and a HR of 1.08 (.97-1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (-3.0% to 3.7%) and a HR of 1.09 (.96-1.25)., Conclusions: InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART., (© 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.)

: As policies built on 'Undetectable = Untransmittable' become more popular, use of durable viral suppression (DVS) as an outcome in analyses is increasing. We identified a case series of recent HIV-related publications that study the DVS outcome. The majority did not distinguish between a definition of DVS and the operationalization of that definition. Clearer discussion of DVS, including a formal definition, is needed to ensure better comparability across studies and ultimately better public health outcomes.

Studies suggest that inflammation might be involved in the pathogenesis of depression. Individuals with human immunodeficiency virus (HIV) have a higher risk of depression and elevated inflammatory profiles. Despite this, research on the link between inflammation and depression among this high-risk population is limited. We examined a sample of men who have sex with men from the Multicenter AIDS Cohort Study in prospective analyses of the association between inflammation and clinically relevant depression symptoms, defined as scores >20 on Center for Epidemiological Studies Depression Scale. We included 1,727 participants who contributed 9,287 person-visits from 1984 to 2010 (8,218 with HIV (HIV+) and 1,069 without (HIV-)). Exploratory factor analysis (EFA) was used to characterize underlying inflammatory processes from 19 immune markers. Logistic regression with generalized estimating equations was used to evaluate associations between inflammatory processes and depressive symptoms stratified by HIV serostatus. Three EFA-identified inflammatory processes (EIPs) were identified. EIP-1 scores-described by soluble tumor necrosis factor receptor 2 (sTNF-R2), soluble interleukin-2 receptor α (sIL-2Rα), sCD27, B-cell activating factor, interferon γ-induced protein 10 (IP-10), soluble interleukin-6 receptor (sIL-6R), sCD14, and sGP130-were significantly associated with 9% higher odds of depressive symptoms in HIV+ participants (odds ratio = 1.09; 95% confidence interval: 1.03, 1.16) and 33% higher odds in HIV- participants (odds ratio = 1.33; 95% confidence interval: 1.09, 1.61). Findings suggest that immune activation might be involved in depression risk among both HIV+ and HIV- men who have sex with men., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: HIV self-testing (HIVST) is a promising approach to expand HIV testing. HIVST is a process in which a person performs an HIV test and interprets the result. Negative HIVST results may encourage men who have sex with men (MSM) to use HIV prevention services. The objective of this study was to examine behaviors (e.g., facility-based HIV testing, condom use) after a negative HIVST test result among Chinese MSM., Methods: We collected data from MSM in eight Chinese cities over a 12-month period. This is a secondary analysis of longitudinal cohort data collected as part of an intervention trial to increase HIV testing. Men completed a survey that described sociodemographic information, sexual behaviors, HIV self-testing, and facility-based HIV testing. Men who completed at least one follow-up survey were included in this analysis. Generalized linear mixed models were used to evaluate whether HIVST increased subsequent facility-based HIV testing and consistent condom use., Results: We included 1219 men. Most men (78.7%) were under 30 years old and had never been married (87.0%). 755 (61.9%) men tested for HIV and 593 (49.3%) men self-tested during the study period. At baseline, among men who had never been tested for HIV, 44.9% (314/699) initiated HIVST during the study period. HIVST was associated with subsequent facility-based testing (aOR of 1.87, 95% CI: 1.47-2.37). HIVST was also associated with subsequent consistent condom use (aOR = 1.53, 95% CI: 1.13-2.06)., Conclusion: HIVST was associated with subsequent facility-based HIV testing and consistent condom use. HIVST may enhance uptake of related HIV prevention services at facilities, suggesting the need for more implementation research.

Social media interventions may enhance HIV services among key populations, including men who have sex with men (MSM). This longitudinal analysis examined the effect of recalling, sharing, and participating in different components of a social media intervention on HIV testing among MSM. The social media intervention included six images/texts and information about an online local community contest to promote testing. Of the 1033 men, they recalled a mean of 2.7 out of six images and shared an average of one image online. 34.5% of men recalled information on the online local community contest and engaged in a mean of 1.3 contest. Recalling images/texts (aOR = 1.13, 95% CI 1.02-1.25) and recalling a local contest (aOR = 1.59, 95% CI 1.13-1.24) were associated with facility-based HIV testing. This study has implications for the development and evaluation of social media interventions to promote HIV testing.

Background: The spread of healthy behaviors through social networks may be accelerated by influential individuals. Previous studies have used lay health influencers to prevent sexually transmitted infections (STIs) among internet-using men who have sex with men (MSM). However, there is a lack of understanding of the characteristics of this key subset of MSM., Objective: This study aimed to examine sociodemographic characteristics, HIV and syphilis testing, and sexual behaviors of Web-based MSM sexual health influencers (SHIs) in China, defined as individuals with relatively stronger influence on spreading HIV and STI information online., Methods: A Web-based survey of MSM was conducted in August 2017 as a final follow-up of a randomized controlled trial promoting HIV testing in 8 Chinese cities. Men were recruited through a gay social networking mobile phone app and were included if they were born biologically male, aged 16 years and above, ever had sex with another man, and HIV negative or with unknown HIV status. Information regarding sociodemographic characteristics, sexual behaviors, and HIV and syphilis testing was obtained. We assessed men's Web-based sexual health influence using a standardized 6-item opinion leadership scale focused on HIV and STI information. Influencers were defined as those whose mean score ranked within the top 13% (a higher score means greater influence). We used multivariable linear and logistic regression models to measure Web-based sexual health influence's association with HIV and syphilis testing, controlling for intervention trial effects, age, education, income, and marital status., Results: Overall, 1031 men completed the survey. Most men were younger than 30 years (819/1031, 79.43%) and had at least college education (667/1031, 64.69%). Influencers were more likely to get tested for HIV (73/132, 55.3% vs 337/899, 37.5%; P<.001) and syphilis (35/132, 26.5% vs 137/899, 15.2%; P=.001) in the last 3 months compared with noninfluencers. There were no significant differences in condomless sex with male partners (26/132, 19.7% vs 203/899, 22.6%; P=.46), mean number of male sex partners (1.32 vs 1.11; P=.16) in the last 3 months, and mainly meeting male sex partners online in the last 12 months (97/132, 73.5% vs 669/899, 74.4%; P=.82) between influencers and noninfluencers. Regression analyses showed that influencers had higher odds of HIV testing (adjusted odds ratio, AOR 2.16, 95% CI 1.48-3.17) and syphilis testing (AOR 1.99, 95% CI 1.28-3.10) in the last 3 months., Conclusions: We identified Web-based SHIs who might be more likely to help promote healthy HIV and syphilis testing behaviors through MSM populations. Leveraging existing influencers may help improve HIV and syphilis testing among their networks., (©Dan Wu, Weiming Tang, Haidong Lu, Tiange P. Zhang, Bolin Cao, Jason J. Ong, Amy Lee, Chuncheng Liu, Wenting Huang, Rong Fu, Katherine Li, Stephen W Pan, Ye Zhang, Hongyun Fu, Chongyi Wei, Joseph D Tucker. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.01.2019.)

Background: HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities., Methods and Findings: An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation., Conclusions: In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC)., Trial Registration: ClinicalTrials.gov NCT02796963., Competing Interests: WT and JDT are advisors to SESH Global. All remaining authors declare that they have no competing interests relevant to this work.

Background Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population. Methods We first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008–2014. Results Of 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2 years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was −0.4 (95% confidence interval: −6.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was −0.9 (95% confidence interval: −6.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio = 0.95, 95% confidence interval: 0.68, 1.32) and −0.7 (95% confidence interval: −6.7, 5.5) for the per-protocol comparison (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). Conclusion No benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population. [ABSTRACT FROM AUTHOR]

A correction for the article "Clinical Effectiveness of Integrase Strand Transfer Inhibitor–Based Antiretroviral Regimens Among Adults With Human Immunodeficiency Virus: A Collaboration of Cohort Studies" is presented, which is published in the September 2020 issue of the periodical.