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Background: For people with HIV and CD4+ counts >500 cells/mm³, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+counts are <350 cells/mm³. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. Methods: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+counts >500 cells/mm³ to immediate treatment initiation after random assignment (n=2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. Results: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm³ in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm³. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm³. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). Conclusions: Among adults with CD4+ counts >500 cells/mm³, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.) In people with HIV and CD4+ counts >500 cells/mm³, immediate initiation of ART reduced serious AIDS and SNA risk, the primary end point, compared with deferring ART until CD4+counts were <350 cells/mm³. Beginning in 2016 after the deferred group was advised to initiate ART, 89 immediate and 113 deferred group participants experienced a primary end point. Persistent excess risk of the primary end point remained in the deferred compared to the immediate ART group. [ABSTRACT FROM AUTHOR]

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART. [ABSTRACT FROM AUTHOR]

Polypharmacy and frailty are correlated in Persons Living with HIV (PLWH) in the United States, but little is known about their correlation in resource-limited settings. Our cross-section study evaluated the correlation between polypharmacy and frailty among Thai 324 virally suppressed PLWH and 132 uninfected patients aged ≥50 between March 2016 and April 2017. The primary predictor was the number of patient-reported non-antiretroviral therapy (ART) medications. The outcome was having additional domain of the five Fried frailty phenotype domains (0 = normal, 1–2 = prefrail, >3 = frail). Most participants were male (63% PLWH, 67% uninfected) with few comorbidities (1.4 PLWH, 0.9 uninfected) and small median number of non-ART medications (2 PLWH, 1 uninfected). Frailty was uncommon (8.6% PLWH, 3.8% uninfected). Each additional non-ART medication correlated with 6% increased likelihood of having additional frailty domain among PLWH (95% CI: 0.002–0.11, p = .04) but not statistically significant among the uninfected. The association between polypharmacy and frailty is more pronounced in Thai PLWH than in participants without HIV. Further study is warranted to confirm this association in other resource-limited settings and explore potential deprescribing practices. [ABSTRACT FROM AUTHOR]

There is limited evidence about the long-term changes in nutritional status among the elderly people living with human immunodeficiency virus (PLWH). We aimed to investigate the changes in nutritional status and related factors over 4 years in the elderly PLWH. The longitudinal study was conducted prospectively among 250 PLWH, 50 years of age and older, receiving antiretroviral therapy (ART). The Mini Nutritional Assessment (MNA) and Thai Depression Scale (TDS) to assess nutritional status and depression, respectively, were performed at the outpatient clinic both at baseline and 4-year follow-up. Majority were male (60.8%) with median age of 58 years. The median CD4 was 612.5 cells/mm3 and 98% had HIV RNA <50 copies/mL. Median duration of ART was 20 years. Median body mass index was 23.1 kg/m2. The most common ART were rilpivirine (45.2%) and dolutegravir (18.8%). Fifty-one patients (20.4%) deteriorated in nutritional status and mean MNA scores declined (25.8 vs. 24.8, p < .001) at follow-up period. In multivariate analysis, high TDS scores (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.17–1.52), polypharmacy (OR, 1.35; 95% CI, 1.10–1.65), and high-density lipoprotein cholesterol (HDL-C) levels (OR, 1.04; 95% CI, 1.01–1.07) were associated factors of deterioration in nutritional status. In this 4-year longitudinal follow-up, 20% of the aging PLWH have deterioration of nutritional status. High TDS scores (depression), polypharmacy, and high HDL-C were significantly associated with declining nutritional status. Our findings highlight the importance of screening and monitoring nutritional and depression status in routine HIV treatment and care for geriatric HIV-infected population. [ABSTRACT FROM AUTHOR]

Data are lacking or outdated on burden of HIV, viral hepatitis infection, and sexually transmitted infections such as syphilis among people deprived of liberty in the Asia-Pacific region. We aimed to evaluate the proportion of viral hepatitis B (HBV), hepatitis C (HCV), HIV, and syphilis infections, and factors associated with HCV, HBV, and HIV infection in a central male prison. A cross-sectional study was performed among 1,028 people deprived of liberty from a central male prison in Bangkok, Thailand. People deprived of liberty were screened for HIV, HBV, HCV, and syphilis infections during 2018–2019. HBV and HCV were defined as positive hepatitis B surface antigen and positive anti-HCV antibody, respectively. Proportions (95% confidence interval [CI]) of infections were calculated based on the binomial distribution. HBV proportion was reported for different age groups. Risk factors associated with HCV infections were evaluated by logistic regression model. The median age was 38 (interquartile range, 32–50) years, and 6.9% reported use of injection drugs. The proportion of HIV, HBV, anti-HCV, HCV RNA, and syphilis was 2.9% (95% CI, 1.9–4.1), 6.4% (5–8.1), 5.9% (4.6–7.6), 4.2% (3–5.6), and 4.8% (3.5–6.3), respectively. One (0.1%), 7 (0.6%), and 2 (3%) were co-infected with HIV/HBV, HIV/HCV, and HDV/HBV, respectively. HBV proportion differed across age groups: 3.7% in <30 years, 7% in 31–40 years, 9.7% in 41–50 years, and 5.5% in >50 years. Factors associated with HCV infection were older age, lower education level, previous incarceration, and injection drug use. In multivariable models, older age was associated with HBV infection, and men having sex with men was associated with HIV infection. The proportion of blood-borne infections was higher among males than among the general population. HBV vaccination, routine HCV screening, and treatment with pan-genotypic direct-acting antivirals with minimal specialist requirements should be implemented in Thai prisons. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) have higher ischemic cerebrovascular disease rates than HIV-negative individuals. We aimed to determine the incidence and risk factors of ischemic stroke (IS) and transient ischemic attack (TIA) among Thai PLWH. Data from adults living with HIV who were enrolled in a prospective HIV-NAT 006 cohort in Bangkok, Thailand, from 1996 to 2020 were included in the analysis. The primary endpoint was first-ever IS or TIA. Among 2020 PLWH included in the analysis, 16 (0.8%) developed first-ever IS/TIA over 23,579 person-years (incidence: 0.7 per 1,000 person-years [95% confidence interval {CI} 0.4–1.1]). Median CD4 cell counts before developing IS/TIA was 480 cells/mL and 87.5% were virologically suppressed. In multivariate models, hypertension was the only factor significantly associated with IS/TIA incidence (adjusted subhazard ratio 4.4; 95% CI 1.2–15.6, p = .02). The incidence of IS/TIA was low among well-suppressed Thai PLWH. Traditional risk factors, particularly hypertension, still play an essential role in developing IS/TIA. [ABSTRACT FROM AUTHOR]

Background: Despite the success of combination antiretroviral therapy (cART), cognitive impairment remains a problem for people living with HIV (PLWH), including those who are virologically suppressed. The presentation and course of cognitive impairment have changed significantly since the introduction of cART. We aimed to determine the trajectory of cognitive performance in a cohort of virologically suppressed aging PLWH. Method: Thai PLWH aged ≥50 years followed in the HIV‐NAT 006 cohort were enrolled during 2015‐2017 to assess cognitive performance using the Thai‐validated Montreal Cognitive Assessment (MoCA), a cutoff of ≥25 as normal. The follow‐up MoCA was consecutively performed since 2021. Participants who had plasma HIV RNA of ≤50 copies/mL and completed the follow‐up MoCA were included in the analysis. Changes in the MoCA scores were calculated between the two visits. Result: Among 181 eligible participants (69 [38.1%] female; mean [SD] age, 57.0 [5.7] years; 46 [25.4%] had education ≤6 years; mean duration of HIV infection, 18.0 [4.2] years), 104 (57.5%) had cognitive impairment at enrollment. There were statistically significantly higher proportion of female sex (45.2% vs 28.6%, p = 0.023) and participants who had education >6 years (85.6% vs 59.4%, p<0.001) among cognitively impaired (CI) than cognitively unimpaired (CU) participants. After mean 5.6 (0.4) years of follow‐up period, the mean difference of the MoCA score was ‐0.72 (95%CI ‐1.29 to ‐0.15, p = 0.01, d = 0.19) and there were statistically significant differences in the MoCA score changes between groups categorized by baseline cognitive performance (mean difference 3.25, 95%CI 2.09 to 4.41, p<0.001, after adjusting for sex assigned at birth, age, education levels, smoking status, depression, hypertension, and diabetes mellitus).The CU group showed a statistically significant decrease in the MoCA score (mean difference ‐2.58, 95%CI ‐3.26 to ‐1.90, p<0.001, d = 0.86), and 43/77 (55.8%) of CU participants developed cognitive impairment at follow‐up, while the CI group had comparable MoCA scores between the two visits (mean difference 0.65, p = 0.09) (figure). Conclusion: CU virologically suppressed PLWH demonstrated a statistically significant reduction in cognitive performance compared to their CI counterparts over time. Further studies on the underlying pathological mechanisms and implementation of cognitive care services among virologically suppressed PLWH are warranted. [ABSTRACT FROM AUTHOR]

Older adults face physiological, psychological, social, and economic changes, which may impair nutritional status, making the body vulnerable to illness and adverse clinical outcomes. Little is known regarding the nutritional status among elderly people living with HIV (PLHIV). We aimed to study the prevalence of malnutrition and the associated factors in a Thai aging cohort. A cross-sectional study was conducted among PLHIV >50 years of age on long-term antiretroviral therapy and HIV-negative controls, frequency matched by sex and age in Bangkok, Thailand. Nutritional status was assessed by the Mini Nutrition Assessment (MNA) tool. Abnormal nutritional status was defined as MNA score <24 (malnutrition and at risk of malnutrition). Body composition was measured by bioelectrical impedance analysis using Body Composition Analyzer. Demographic and disease-related factors were assessed for their association with abnormal nutrition status using multivariable logistic regression. There were 349 PLHIV and 103 HIV-uninfected controls, with median age 55 years. The majority were male (63%) with median body mass index (BMI) of 23.4 kg/m2. PLHIV had lower BMI [median, 23.1 (IQR, 20.8–25.2) vs. 25.3 (22.3–28.7) kg/m2, p < .001], lower fat percent [22.8% vs. 26.3%, p < .001] and lower fat mass [14.2 vs. 16.9 kg, p < .001] and higher abnormal nutritional status (18.05% vs. 6.8%, p = .005) than controls. In the multivariate model, older age (adjusted odds ratio [aOR], 1.06, 95% confident interval [CI]: 1.01–1.12, p = .03), positive HIV status (aOR, 2.67, 95% CI: 1.07–6.65, p = .036), diabetes mellitus (aOR, 2.21, 95% CI: 1.003–4.87, p = .049), lower fat mass (aOR, 0.70, 95%CI: 0.57–0.86, p < .001), and lower BMI (aOR, 0.63, 95% CI: 0.51–0.78, p < .001) were independently associated with abnormal nutritional status. PLHIV had higher risks for abnormal nutritional status compared with HIV-uninfected individuals. Regular screening and monitoring of nutritional status among PLHIV may promote better health outcomes. [ABSTRACT FROM AUTHOR]

Background: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is a multicenter, randomized, placebo-controlled trial, designed to test whether a statin medication can prevent cardiovascular disease in people with HIV. REPRIEVE recently completed enrollment of 7557 participants at over 100 clinical sites globally. Participant groups of focus were women, and racial and ethnic minorities. Objective: To describe recruitment methods and strategies developed by the REPRIEVE Clinical Coordinating Center (CCC) and share best practices learned from the recruitment process. Methods: Enrollment targets were agreed upon with the primary funder, the National Heart, Lung, and Blood Institute (NHLBI) and were milestone driven. Milestones included number of sites activated, number of participants enrolled within specific time frames, and proportion of women and minorities enrolled. Strategies to achieve these milestones included structured interviews with site-designated REPRIEVE Recruitment Champions to develop best practices, development of a multimedia campaign, and site level recruitment support. Results: Recruitment initiated March, 2015 and completed March, 2019. The final accrual target was 7500 participants over 48 months. The trial met this target within the time specified. Overall, 10,613 screens were completed, 48% of participants enrolled from sites outside of North America, 32% were female, 44% were Black or African American, and 25% were Hispanic or Latino. Conclusions: REPRIEVE met its overall projected recruitment goal by using multiple, simultaneous strategies to specifically target a diverse population including minority subgroups. REPRIEVE benefited from the development of recruitment strategies with clear targets and communication of accrual targets to study teams. [ABSTRACT FROM AUTHOR]

Neurocognitive impairment (NCI) contributes to poor quality of life among HIV-positive individuals. Cardiovascular risk factors, including the predictor of subclinical atherosclerosis, carotid intima-media thickness (cIMT), are reported to be associated with NCI. Data on NCI and its association with cIMT among HIV positive are limited, especially in Asian populations. We aimed to determine the prevalence of NCI and its association with cIMT among HIV-positive and HIV-negative aging Thai individuals. Cognitive performance was evaluated by the Thai version of Montreal Cognitive Assessment (MoCA) with a cutoff of <25/30 for diagnosis of NCI. Depression was evaluated by PHQ-9 Patient Depression Questionnaire, with scores ≥5 indicating depression. cIMT measurement was performed by experienced neurologists, and abnormal cIMT was defined as cIMT ≥0.9 mm or presence of carotid plaques. Among 340 well suppressed and aging HIV-positive and 102 HIV-negative matched participants, the median age (interquartile range) was 55 (52–59) years and 61.5% were males. For HIV positive group, the median duration on antiretroviral therapy was 18.3 years with median CD4 of 615.5 cells/mm3, and 97.4% had current plasma HIV RNA <50 copies/mL. The most common antiretroviral agents used were tenofovir disoproxil fumarate (76.8%), lamivudine (70.3%), efavirenz (26.7%), and emtricitabine (23.8%). HIV-positive and HIV-negative participants performed comparably between each domain and had comparable prevalence of NCI (59.4% vs. 61.7%, p = .69). However, the HIV-positive group had a high prevalence of depression (24.71% vs. 13.73%, p = .019). HIV-positive status [adjusted odd ratio (aOR) 0.91; 95% confidence interval (CI) 0.57–1.47, p = .71] and cIMT (aOR 1.17; 95% CI 0.77–1.79, p = .47) were not significantly associated with NCI. Given the high prevalence of NCI and depression among aging HIV-positive individuals, routine screening for NCI and depression should be integrated into the HIV care services. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks. Objective: In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction. Methods: Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF. Results: Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts < 200 cells/uL and VL > 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies. [ABSTRACT FROM AUTHOR]

Vitamin D, which is important for calcium homeostasis and bone metabolism, has several noncalcemic actions. Low vitamin D levels have been observed in HIV-infected patients from high latitudes, with consequently reduced bone mineral density (BMD), but data from the tropics are scarce. We aimed to determine the prevalence of and risk factors for hypovitaminosis D among HIV-infected patients in the tropics. This was a cross-sectional study to determine serum 25-hydroxyvitamin D [25(OH)D] levels in HIV-infected patients who attended our HIV clinic in Bangkok, Thailand from July 2010 to June 2011. Hypovitaminosis D was defined as vitamin D insufficiency and deficiency [25(OH)D 20-30 ng/ml and <20 ng/ml, respectively]. Hypovitaminosis D prevalence was calculated and risk factors were determined using multivariate logistic regression. A total of 673 HIV-infected adults were included. The median age was 41 years and 47% were females. The median body mass index (BMI) was 21.9 kg/m2 and 93% were using antiretroviral therapy (ART), with a median (IQR) duration of 8.9 (5.0-10.4) years. Thirty-one percent were using efavirenz (EFV). The prevalence of vitamin D insufficiency and deficiency was 40.6% and 29.9%, respectively. In multivariate analysis, female gender [odds ratio: OR (95% confidence interval: 95% CI) 1.7 (1.2-2.3), p = 0.005], age >37 years [OR (95% CI) 1.6 (1.1-2.4), p = 0.01], and EFV use [OR (95% CI) 2.0 (1.3-3.2), p = 0.004] were independent predictors of hypovitaminosis D. Even in tropical areas where the sun is abundant, hypovitaminosis D is highly prevalent. Thus, treatment of low vitamin D in HIV-infected patients at high risk should not be ignored to prevent reductions in BMD and other hypovitaminosis D-related comorbidities. [ABSTRACT FROM AUTHOR]