METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.
RESULTS: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.
CONCLUSION: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.
METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.
RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.
CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.
METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.
RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.
CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).
METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created.
RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2(OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p 350 cells/mm3(OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p 2000 cells/mm3(OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients.
CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.
DESIGN: A randomized, double-blind, placebo-controlled trial was conducted among incarcerated individuals with HIV and AUDs transitioning to the community from 2010 through 2016.
METHODS: Eligible participants (N = 100) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 67) or placebo (n = 33) starting at release and continued for 6 months. The primary and secondary outcomes were the proportion that maintained or improved VS at <200 and <50 copies per milliliter from baseline to 6 months, respectively, using an intention-to-treat analysis.
RESULTS: Participants allocated to XR-NTX improved VS from baseline to 6 months for <200 copies per milliliter (48.0%-64.2%, P = 0.024) and for <50 copies per milliliter (31.0%-56.7%, P = 0.001), whereas the placebo group did not (<200 copies/mL: 64%-42.4%, P = 0.070; <50 copies/mL: 42.0%-30.3%, P = 0.292). XR-NTX participants were more likely to achieve VS than the placebo group at 6 months (<200 copies/mL: 64.2% vs. 42.4%; P = 0.041; <50 copies/mL: 56.7% vs. 30.3%; P = 0.015). XR-NTX independently predicted VS [<200 copies/mL: adjusted odds ratio (aOR) = 2.68, 95% confidence interval (CI) = 1.01 to 7.09, P = 0.047; <50 copies/mL: aOR = 4.54; 95% CI = 1.43 to 14.43, P = 0.009] as did receipt of ≥3 injections (<200 copies/mL: aOR = 3.26; 95% CI = 1.26 to 8.47, P = 0.010; <50 copies/mL: aOR = 6.34; 95% CI = 2.08 to 19.29, P = 0.001). Reductions in alcohol consumption (aOR = 1.43, 95% CI = 1.03 to 1.98, P = 0.033) and white race (aOR = 5.37, 95% CI = 1.08 to 27.72, P = 0.040) also predicted VS at <50 copies per milliliter.
CONCLUSIONS: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV and AUDs.
METHODS: Randomized trials, assessing the efficacy of antiviral drugs for HBV and HIV co-infected patients were searched in health-related databases. The methodological quality of the included trials was evaluated using the Cochrane risk of bias tool. Main outcome in this meta-analysis study was the success of treatment by antivirals as determined by virologic response. We performed pairwise and network meta-analysis of these trials and assessed the quality of evidence using the GRADE approach.
RESULTS: Seven randomized trials (329 participants) were included in this network meta-analysis study. A network geometry was formed with six treatment options including four antiviral drugs, adefovir (ADV), emtricitabine (FTC), lamivudine (LMV) and tenofovir disoproxil fumarate (TDF), combination treatment of TDF plus LMV, and placebo. The weighted percentage contributions of each comparison distributed fairly equally in the entire network of evidence. An assumption of consistency required for network meta-analysis was not violated (the global Wald test for inconsistency: Chi2(4) = 3.63, p = 0.46). The results of estimates showed no differences between the treatment regimens in terms of viral response for treating HBV and HIV co-infected patients, which spanned both benefit and harm (e.g. LMV vs TDF plus LMV: OR: 0.37, 95%CI: 0.06-2.41). Overall, the certainty of evidence was very low in all comparisons (e.g. LMV vs TDF plus LMV: 218 fewer per 1000,121 more to 602 fewer, very low certainty). Therefore, we remained uncertain to the true ranking of the antiviral treatments in HBV/ HIV co-infected patients.
CONCLUSIONS: The findings suggest that the evidence is insufficient to provide guidance to the relative effectiveness of currently available antiviral drugs with dual activity in treating co-infection of HBV/HIV. Well-designed, large clinical trials in this field to address other important outcomes from different epidemiological settings are recommended.
SETTING: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.
METHODS: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.
RESULTS: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.
CONCLUSIONS: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.
METHODS: As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis.
RESULTS: Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to "at-risk" men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours.
CONCLUSIONS: This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those taking it may be stigmatized, it is crucial that the use of PrEP is presented as a responsible course of action, and one of a range of strategies that men can use to keep themselves safe from HIV.
METHODS: 126 detoxified heroin-dependent patients, from an outpatient research clinic and detoxification programme in Malaysia, were randomly assigned by a computer-generated randomisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone (n=43), buprenorphine (n=44), or placebo (n=39). Medications were administered on a double-blind and double-dummy basis. Primary outcomes, assessed by urine testing three times per week, were days to first heroin use, days to heroin relapse (three consecutive opioid-positive urine tests), maximum consecutive days of heroin abstinence, and reductions in HIV risk behaviours over 6 months. The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00383045.
FINDINGS: We observed consistent, linear contrasts in days to first heroin use (p=0.0009), days to heroin relapse (p=0.009), and maximum consecutive days abstinent (p=0.0007), with all results best for buprenorphine and worst for placebo. Buprenorphine was associated with greater time to first heroin use than were naltrexone (hazard ratio 1.87 [95% CI 1.21-2.88]) or placebo (2.02 [1.29-3.16]). With buprenorphine, we also recorded significantly greater time to heroin relapse (2.17 [1.38-3.42]), and maximum consecutive days abstinent than with placebo (mean days 59 [95% CI 43-76] vs 24 [13-35]; p=0.003); however, for these outcomes, differences between buprenorphine and naltrexone were not significant. Differences between naltrexone and placebo were not significant for any outcomes. HIV risk behaviours were significantly reduced from baseline across all three treatments (p=0.003), but the reductions did not differ significantly between the three groups.
INTERPRETATION: Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence.
METHODS: Blood donation data of 4120 donors, spanning from January to December 2020, were retrospectively reviewed. The blood were screened for TTI markers, including hepatitis B surface antigen (HBsAg), anti-hepatitis B core (anti-HBc), anti-hepatitis C virus (anti-HCV), anti-human immunodeficiency viruses 1 and 2 (anti-HIV1&2), anti-human T-lymphotropic virus types 1 and 2 (anti-HTLV-1&2), and syphilis antigen.
RESULTS: Positive TTI markers were detected in 10.9% of the donors. The most detected TTI marker was anti-HBc (8.9%), followed by HBsAg (0.7%). Other markers were individually detected in <1% of the donors. Anti-HBc-positive was significantly elevated among non-Saudi blood donors. There was an association between age groups and anti-HCV (p=0.002), anti-HTLV (p=0.004) and syphilis antigen (p=0.02) markers positivity. The AB positive blood group exhibited the most positivity for TTI markers, followed by O positive blood group. Similarly, association was found between ABO group and HBsAg (p=0.01), anti-HBc (p=0.001), and anti-HCV (p<0.001) markers positivity.
CONCLUSION: Emphasis on implementing robust screening measures for donated blood is underscored by this study. There is the need for future study to extensively evaluate TTI status to enhance our understanding of the trend in TTI.
METHODS: PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two-hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.
RESULTS AND DISCUSSION: Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow-up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person-years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow-up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p 50 years: HR = 4.19, 95% CI 2.12 to 8.28, p 30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2 , and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).
CONCLUSIONS: Type 2 DM in HIV-infected Asians was associated with later years of follow-up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non-communicable diseases including DM as PLHIV age.