Displaying publications 1 - 20 of 31 in total

Abstract:
Sort:
  1. Papot E, Jacoby S, Arlinda D, Avihingsanon A, Azwa I, Borok M, et al.
    HIV Res Clin Pract, 2022 Jul 19;23(1):37-46.
    PMID: 35938597
    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.
  2. Boettiger DC, Law MG, Ross J, Huy BV, Heng B, Ditangco R, et al.
    Journal of virus eradication, 2020 Feb 20;6(1):11-18.
    PMID: 32175086
    Objectives: Integration of HIV and non-communicable disease services improves the quality and efficiency of care in low- and middle-income countries (LMICs). We aimed to describe current practices for the screening and management of atherosclerotic cardiovascular disease (ASCVD) among adult HIV clinics in Asia.

    Methods: Sixteen LMIC sites included in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific network were surveyed.

    Results: Sites were mostly (81%) based in urban public referral hospitals. Half had protocols to assess tobacco and alcohol use. Protocols for assessing physical inactivity and obesity were in place at 31% and 38% of sites, respectively. Most sites provided educational material on ASCVD risk factors (between 56% and 75% depending on risk factors). A total of 94% reported performing routine screening for hypertension, 100% for hyperlipidaemia and 88% for diabetes. Routine ASCVD risk assessment was reported by 94% of sites. Protocols for the management of hypertension, hyperlipidaemia, diabetes, high ASCVD risk and chronic ischaemic stroke were in place at 50%, 69%, 56%, 19% and 38% of sites, respectively. Blood pressure monitoring was free for patients at 69% of sites; however, most required patients to pay some or all the costs for other ASCVD-related procedures. Medications available in the clinic or within the same facility included angiotensin-converting enzyme inhibitors (81%), statins (94%) and sulphonylureas (94%).

    Conclusion: The consistent availability of clinical screening, diagnostic testing and procedures and the availability of ASCVD medications in the Asian LMIC clinics surveyed are strengths that should be leveraged to improve the implementation of cardiovascular care protocols.

  3. Khuon D, Rupasinghe D, Saphonn V, Kwong TS, Widhani A, Chaiwarith R, et al.
    HIV Med, 2023 Feb;24(2):139-152.
    PMID: 35748404 DOI: 10.1111/hiv.13351
    BACKGROUND: Non-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations.

    METHODS: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23-24.9 kg/m2 ), and obese (≥25 kg/m2 ). High FBG was defined as a single post-ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site.

    RESULTS: A total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29-41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person-years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m2 ) compared with normal weight (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 1.31-2.44; p 25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used.

  4. Avihingsanon A, Lu H, Leong CL, Hung CC, Koenig E, Kiertiburanakul S, et al.
    Lancet HIV, 2023 Oct;10(10):e640-e652.
    PMID: 37494942 DOI: 10.1016/S2352-3018(23)00151-0
    BACKGROUND: For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks.

    METHODS: We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per μL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HIV-1 RNA or HBV DNA result while on study drug. Safety endpoints were assessed in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03547908.

    FINDINGS: Between May 30, 2018 and March 16, 2021, 381 participants were screened, of whom 243 initiated treatment (121 in the receive bictegravir, emtricitabine, and tenofovir alafenamide group; 122 in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group). At week 48, both endpoints met the criteria for non-inferiority: 113 (95%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 111 (91%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HIV-1 RNA less than 50 copies per mL (difference 4·1, 95% CI -2·5 to 10·8; p=0·21), and 75 (63%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus 53 (43%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HBV DNA suppression (difference 16·6, 5·9 to 27·3; nominal p=0·0023). Drug-related adverse events up to week 96 occurred in 35 (29%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 34 (28%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group. One (1%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group reported a serious adverse event (cryptococcal meningitis attributed to immune reconstitution inflammatory syndrome) that was deemed to be treatment-related.

    INTERPRETATION: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is an effective therapy for adults with HIV-1 and HBV coinfection starting antiviral therapy.

    FUNDING: Gilead Sciences.

  5. Jiamsakul A, Gani Y, Avihingsanon A, Azwa I, Chaiwarith R, Khusuwan S, et al.
    J Acquir Immune Defic Syndr, 2022 Nov 01;91(3):290-295.
    PMID: 35969472 DOI: 10.1097/QAI.0000000000003067
    BACKGROUND: Linkage studies have reported high rates of previously unascertained mortality among people living with HIV (PLHIV) who have been lost to follow-up (LTFU). We assessed survival outcomes among PLHIV who were LTFU in Thailand and Malaysia, through linkages to a national death registry or HIV database.

    METHODS: Data linkages with the national death registry or national HIV database were conducted in 2020 on all PLHIV who met LTFU criteria while enrolled in care at participating HIV clinical sites. LTFU was defined as having no documented clinical contact in the previous year, excluding transfers and deaths. Survival time was analyzed using the Cox regression, stratified by site.

    RESULTS: Data linkages were performed for 489 PLHIV who had been LTFU at sites in Malaysia (n = 2) and Thailand (n = 4). There were 151 (31%) deaths after being LTFU; the mortality rate was 4.89 per 100 person-years. Risk factors for mortality after being LTFU were older age [41-50 years: hazard ratio (HR) = 1.99, 95% confidence interval (CI): 1.08 to 3.68; and older than 50 years: HR = 4.93, 95% CI: 2.63 to 9.22; vs. age 30 years or younger]; receiving NRTI + PI (HR = 1.87, 95% CI: 1.22 to 2.85 vs. NRTI + NNRTI); positive hepatitis C antibody (HR = 2.25, 95% CI: 1.40 to 3.62); and having previous AIDS illness (HR = 1.45, 95% CI: 1.03 to 2.05). An improved survival was seen with a higher CD4 count (CD4 351-500 cells/µL: HR = 0.40, 95%CI: 0.21-0.76; and CD4 >500 cells/µL: HR = 0.43, 95%CI: 0.25-0.75; vs. CD4 ≤200 cells/µL).

    CONCLUSIONS: Almost one-third of PLHIV who were LTFU in this cohort had died while out of care, emphasizing the importance of efforts to reengage PLHIV after they have been LTFU and ensure they have access to ongoing ART.

  6. Han WM, Avihingsanon A, Rajasuriar R, Tanuma J, Mundhe S, Lee MP, et al.
    J Acquir Immune Defic Syndr, 2023 Feb 01;92(2):180-188.
    PMID: 36625858 DOI: 10.1097/QAI.0000000000003121
    BACKGROUND: We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization.

    METHODS: All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling.

    RESULTS: A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29-43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09-0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory.

    CONCLUSIONS: INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration.

  7. Bijker R, Kumarasamy N, Kiertiburanakul S, Pujari S, Lam W, Chaiwarith R, et al.
    Antivir Ther, 2019;24(4):271-279.
    PMID: 30833516 DOI: 10.3851/IMP3298
    BACKGROUND: We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort.

    METHODS: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation.

    RESULTS: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL.

    CONCLUSIONS: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.

  8. Bijker R, Jiamsakul A, Uy E, Kumarasamy N, Ditango R, Chaiwarith R, et al.
    HIV Med, 2019 03;20(3):183-191.
    PMID: 30620108 DOI: 10.1111/hiv.12687
    OBJECTIVES: With aging of the HIV-positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD-related and other causes of death (CODs) and factors associated with CVD in a multi-country Asian HIV-positive cohort.

    METHODS: Patient data from 2003-2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow-up. Cumulative incidences were plotted for CVD-related, AIDS-related, non-AIDS-related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD.

    RESULTS: Of 8069 patients with a median follow-up of 7.3 years [interquartile range (IQR) 4.4-10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person-years (PY)], and this total included 22 CVD-related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub-hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36-3.58 for age 41-50 years; sHR 5.52; 95% CI 3.43-8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04-2.52), high total cholesterol (sHR 1.89; 95% CI 1.27-2.82), high triglycerides (sHR 1.55; 95% CI 1.02-2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12-2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle- and upper middle-income countries.

    CONCLUSIONS: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle-income countries may indicate under-diagnosis of CVD in Asian-Pacific resource-limited settings.

  9. Durier N, Yunihastuti E, Ruxrungtham K, Kinh NV, Kamarulzaman A, Boettiger D, et al.
    J Viral Hepat, 2017 03;24(3):187-196.
    PMID: 27917597 DOI: 10.1111/jvh.12630
    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).
  10. Ku SW, Jiamsakul A, Joshi K, Pasayan MKU, Widhani A, Chaiwarith R, et al.
    J Int AIDS Soc, 2019 Mar;22(3):e25264.
    PMID: 30924281 DOI: 10.1002/jia2.25264
    INTRODUCTION: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV-infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear.

    METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.

    RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.

    CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

  11. Han WM, Jiamsakul A, Kiertiburanakul S, Ng OT, Sim BL, Sun LP, et al.
    J Int AIDS Soc, 2019 Jan;22(1):e25236.
    PMID: 30697944 DOI: 10.1002/jia2.25236
    INTRODUCTION: Comorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new-onset DM among PLHIV in Asian settings.

    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.

  12. Rupasinghe D, Kiertiburanakul S, Kamarulzaman A, Zhang F, Kumarasamy N, Chaiwarith R, et al.
    HIV Med, 2020 07;21(6):397-402.
    PMID: 31852025 DOI: 10.1111/hiv.12836
    OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific.

    METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count  1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.

    RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI)  100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.

    CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

  13. Pasayan MKU, S Mationg ML, Boettiger D, Lam W, Zhang F, Ku SW, et al.
    J Acquir Immune Defic Syndr, 2019 04 01;80(4):436-443.
    PMID: 30550488 DOI: 10.1097/QAI.0000000000001933
    BACKGROUND: Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.

    METHODS: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation.

    RESULTS: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation.

    CONCLUSIONS: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.

  14. Andrieux-Meyer I, Tan SS, Thanprasertsuk S, Salvadori N, Menétrey C, Simon F, et al.
    Lancet Gastroenterol Hepatol, 2021 Jun;6(6):448-458.
    PMID: 33865507 DOI: 10.1016/S2468-1253(21)00031-5
    BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.

    METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.

    FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.

    INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.

    FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

  15. Rupasinghe D, Choi JY, Yunihastuti E, Kiertiburanakul S, Ross J, Ly PS, et al.
    J Med Virol, 2022 Nov;94(11):5451-5464.
    PMID: 35869413 DOI: 10.1002/jmv.28019
    Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p 
  16. Kiertiburanakul S, Boettiger D, Ng OT, Van Kinh N, Merati TP, Avihingsanon A, et al.
    AIDS Res Ther, 2017;14:27.
    PMID: 28484509 DOI: 10.1186/s12981-017-0151-1
    BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome.

    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.

  17. Rajasuriar R, Chong ML, Ross JL, Jiamsakul A, Avihingsanon A, Lee MP, et al.
    AIDS, 2023 Apr 01;37(5):823-835.
    PMID: 36728672 DOI: 10.1097/QAD.0000000000003474
    BACKGROUND: Depression and substance use (SU) disorders are prevalent among people with HIV (PWH) and impact health outcomes despite successful antiretroviral therapy (ART). We explored quality of life, functional ability and associated factors among PWH screened positive for depression and/or SU.

    METHODS: This cross-sectional study recruited adult PWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using Patient Health Questionnaire-9 and SU using Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Factors associated with mean QoL and disability scores were analysed using linear regression.

    RESULTS: Of 864 PWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PWH reporting previous trauma/stress (difference = 2.7, 95% confidence interval [CI] 1.5-3.9, P  

  18. Han WM, Jiamsakul A, Salleh NAM, Choi JY, Huy BV, Yunihastuti E, et al.
    J Int AIDS Soc, 2021 05;24(5):e25736.
    PMID: 34021711 DOI: 10.1002/jia2.25736
    INTRODUCTION: Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia-Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS-defining events and mortality among PWID receiving antiretroviral therapy (ART).

    METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load <1000 copies/mL) were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis.

    RESULTS: Of 622 PWID from 12 countries in the Asia-Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre-ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year-10 (n = 78). Higher follow-up HIV viral load and pre-ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2-, 5- and 10-years following ART initiation. There were 52 new AIDS-defining events and 50 deaths during 3347 person-years of follow-up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS-defining event and death.

    CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.

  19. Crane M, Avihingsanon A, Rajasuriar R, Velayudham P, Iser D, Solomon A, et al.
    J Infect Dis, 2014 Sep 1;210(5):745-51.
    PMID: 24585898 DOI: 10.1093/infdis/jiu119
    We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.
  20. Lundgren JD, Babiker AG, Sharma S, Grund B, Phillips AN, Matthews G, et al.
    NEJM Evid, 2023 Mar;2(3).
    PMID: 37213438 DOI: 10.1056/evidoa2200302
    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.).

Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links