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Objective Patients with haemophilia and HIV who acquire hepatitis C virus (HCV) after receiving contaminated blood products can experience accelerated progression of liver fibrosis and a poor prognosis, making liver disease a prominent cause of mortality among these patients. In the current study, we aimed to evaluate the safety and tolerability of the potential antifibrotic agent OP-724—a CREB-binding protein/β-catenin inhibitor—in this patient subset.Design In this single-centre, open-label, non-randomised, phase I trial, we sequentially enrolled patients with cirrhosis following HIV/HCV coinfection classified as Child-Pugh (CP) class A or B. Five patients received an intravenous infusion of OP-724 at doses of 140 or 280 mg/m2 for 4 hours two times weekly over 12 weeks. The primary endpoint was the incidence of serious adverse events (SAEs). Secondary endpoints included the incidence of AEs and improved liver stiffness measure (LSM), as determined by vibration-controlled transient elastography. This study was registered at ClinicalTrials.gov (NCT04688034).Results Between 9 February 2021 and 5 July 2022, five patients (median age: 51 years) were enrolled. All five patients completed 12 cycles of treatment. SAEs were not observed. The most common AEs were fever (60%) and gastrointestinal symptoms (diarrhoea: 20%, enterocolitis: 20%). Improvements in LSM and serum albumin levels were also observed.Conclusion In this preliminary assessment, intravenous administration of 140 or 280 mg/m2/4 hours OP-724 over 12 weeks was well tolerated by patients with haemophilia combined with cirrhosis due to HIV/HCV coinfection. Hence, the antifibrotic effects of OP-724 warrant further assessment in patients with cirrhosis.Trial registration number NCT04688034.

Abstract Socially marginalized groups, including people living with HIV/AIDS (PLHIV), could be disproportionately affected by Coronavirus disease 2019 (COVID-19). Following an initial single-center survey conducted in 2020, we conducted a second survey of 11 antiretroviral therapy (ART) sites in Northern Vietnam between June 2021 and January 2022. We tested anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) nucleocapsid IgG antibodies and assessed prevention against COVID-19 and impacts of COVID-19 on access to ART, economic security, risky health behaviors, and mental health using self-reported questionnaires. In total, 7808 PLHIV on ART participated in the second survey. The overall prevalence of SARS-CoV-2 antibody was as low as 1.2%. There was no clear upward trend in COVID-19 infection among PLHIV compared with the rate of infection among the general population. HIV treatment was generally maintained and no increase in risky health behaviors was observed. The economic impacts were significant, with high unemployment rate, poorer economic security, and binge drinking strongly associated with depression. However, the prevalence of depression decreased by 11.2% compared with pre-COVID-19 levels. Social support, including for patients to continue HIV treatment and effective employment/financial assistance, may help to alleviate the negative socioeconomic impacts of COVID-19 and improve mental health among PLHIV.

IntroductionToxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific.MethodsThis study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression.ResultsA total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/μL and 162 (78.6%) had CD4 ≤100 cells/μL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/μL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/μL: OR 0.14, 95% CI 0.06-0.34; >200 cells/μL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/μL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis.ConclusionsSymptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH.

Abstract Introduction Common mental disorders (CMDs) are highly prevalent among people with HIV. Integrating mental healthcare into HIV care may improve mental health and HIV treatment outcomes. We describe the reported availability of screening and treatment for depression, anxiety and post‐traumatic stress disorder (PTSD) at global HIV treatment centres participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium in 2020 and changes in availability at sites in low‐ or middle‐income countries (LMICs) between 2016/2017 and 2020. Methods In 2020, 238 sites contributing individual‐level data to the IeDEA Consortium and in 2016/2017 a stratified random sample of IeDEA sites in LMICs were eligible to participate in site surveys on the availability of screening and treatment for CMDs. We assessed trends over time for 68 sites across 27 LMICs that participated in both surveys. Results Among the 238 sites eligible to participate in the 2020 site survey, 227 (95%) participated, and mental health screening and treatment data were available for 223 (98%) sites across 41 countries. A total of 95 sites across 29 LMICs completed the 2016/2017 survey. In 2020, 68% of sites were in urban settings, and 77% were in LMICs. Overall, 50%, 14% and 12% of sites reported screening with a validated instrument for depression, anxiety and PTSD, respectively. Screening plus treatment in the form of counselling was available for depression, anxiety and PTSD at 46%, 13% and 11% of sites, respectively. Screening plus treatment in the form of medication was available for depression, anxiety and PTSD at 36%, 11% and 8% of sites, respectively. Among sites that participated in both surveys, screening for depression was more commonly available in 2020 than 2016/2017 (75% vs. 59%, respectively, p = 0.048). Conclusions Reported availability of screening for depression increased among this group of IeDEA sites in LMICs between 2016/2017 and 2020. However, substantial gaps persist in the availability of mental healthcare at HIV treatment sites across global settings, particularly in resource‐constrained settings. Implementation of sustainable strategies to integrate mental health services into HIV care is needed.

Summary: Background: Japan has a concentrated HIV epidemic, with the majority of transmission among men who have sex with men (MSM). This study aimed to explore the effect of behavioral and biomedical interventions on the HIV epidemic and forecast the time required to eliminate HIV transmission among Japanese MSM. Methods: A deterministic compartmental model was built to estimate and forecast the HIV epidemic among Japanese MSM from 2010 to 2050. Elimination of HIV transmission among MSM was defined as incidence less than 1/1000 person-years. The time required for eliminating HIV transmission under different scenarios was calculated. Findings: Under the current policies, HIV transmission cannot be eliminated by 2050. Both behavioral and biomedical interventions can achieve elimination of HIV among MSM by 2050 with annual number of sexual partners among high-risk MSM less than 9, or with condom use rate above 65%, or with testing and treatment rate above 80%, or with more than 10% PrEP coverage rate. Under comprehensive interventions, HIV elimination will be achieved in 2032, 2025 and 2024 using weak, moderate and strong intervention combinations, respectively. Interpretation: Both behavioural and biomedical interventions can achieve elimination of HIV among MSM by 2050, but comprehensive interventions can accelerate the realization of this goal with higher feasibility. Funding: This study was funded by a Health and Labor Sciences Research Grant (Research on HIV/AIDS) from The Ministry of Health Labour and Welfare (21HB0701) and National Natural Science Foundation of China (No. 81773543 and 81973150), and the KC Wong Education Foundation.

The use of holding regimens for people living with HIV (PLWH) without effective antiretroviral options can have effects on outcomes and future treatment options. We aimed to investigate the use of holding regimens for PLWH in Asian countries. Data from adults enrolled in routine HIV care in IeDEA Asia-Pacific cohorts were included. Individuals were considered to be on holding regimen if they had been on combination antiretroviral therapy for at least 6 months, had two confirmed viral loads (VL) ≥1000 copies/mL, and had remained on the same medications for at least 6 months. Survival time was analyzed using Fine and Gray's competing risk regression. Factors associated with CD4 changes and VL 50 years compared to age 31-40 years (sub-hazard ratio [SHR] 3.29, 95% CI 1.45-7.43, p = 0.004), and VL ≥1000 copies/ml compared to VL