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.
METHODS: We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB after randomization. Baseline factors associated with TB were analyzed using Cox regression stratified by site.
RESULTS: TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa, and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI: 2.1 to 5.1). Increased TB risk was associated with a low CD4+-cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (<150 ×109/L), and low total serum cholesterol (≤4.5 mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+-cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure.
DISCUSSION: The risk of TB remains elevated in PLHIV in the setting of second-line HIV therapy in TB endemic regions. TB was associated with a greater risk of death. Finding that low CD4+ T-cell count was significantly associated with poor outcomes in this population supports the value of CD4+ monitoring in HIV clinical management.
Objective: The objective was to determine the survival rates and prognostic factors of survival in HIV-infected adults treated with ART in Malaysia.
Materials and Methods: This retrospective cohort study considered all HIV-positive adult patients registered in Sungai Buloh Hospital, a major referral center in Malaysia, between January 1, 2007 and December 31, 2016. Then, patients were selected through a systematic sampling method. Demographic, clinical, and treatment data were extracted from electronic medical records. Person-years at risk and incidence of mortality rate per 100 person-years were calculated. The Kaplan-Meier survival curve and log-rank test were used to compare the overall survival rates. Cox proportional hazards regression was applied to determine the prognostic factors for survival.
Results: A total of 339 patients were included. The estimated overall survival rates were 93.8%, 90.4%, 84.9%, and 72.8% at 1, 3, 5, and 10 years, respectively, from ART initiation. The results of multiple Cox proportional hazard regression indicated that anemic patients were at a 3.76 times higher risk of mortality (95% confidence interval [CI]: 1.97-7.18; P < 0.001). The hazard risk was 2.09 times higher for HIV patients co-infected with tuberculosis (95% CI: 1.10, 3.96; P = 0.024).
Conclusion: The overall survival rates among HIV-infected adults in this study are higher than that from low-income countries but lower than that from high-income countries. Low baseline hemoglobin levels of <11 g/dL and tuberculosis co-infection were strong prognostic factors for survival.
DISCUSSION: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic.
CONCLUSIONS: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind.
METHODS: Adults > 18 years of age on second-line ART for ≥ 6 months were eligible. Cross-sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia-Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3-6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS-USA 2019 mutations list. VF risk factors were analysed using logistic regression.
RESULTS: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second-line switch, median [interquartile range (IQR)] age was 37 (32-42) years and median (IQR) CD4 count was 103 (43.5-229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17-0.77 vs. CD4 ≤ 50) and HIV exposure through male-male sex (OR = 0.32, 95% CI: 0.17-0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12-0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more.
CONCLUSIONS: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second-line regimens.
METHODS: The standard forward-backwards translation technique was used to convert English version of the WHOQOL HIV Bref into Urdu. After cognitive debriefing, final Urdu version of instrument was developed. Based on the principle of at least 5 subjects for each item, a sample of 182 patients was used using a universal random sampling technique from the Pakistan Institute of Medical Sciences, Islamabad. The Cronbach's alpha and intra-class correlation coefficients (ICC) were estimated to assess internal validity and reliability of the translated version. Exploratory factor analysis was carried out to determine the factor structure and independent associations between the instrument domains and CD-4T-cell count were assessed using multivariable linear regression RESULTS: High Cronbach alpha 0.93 was found for all WHOQOL HIV Bref facets. The test-retest reliability demonstrated a statistically significant ICC ranged from 0.88 to 0.98 (p HIV Bref is a psychometrically valid and culturally well-adapted HRQoL measurement tool for PLWHA in Pakistan.
METHODS: We searched for peer-reviewed studies in online databases. To be eligible for inclusion in this review, studies must have involved a population or sub-population of PWUD engaged in MMT; report improved uptake of HIV testing, exposure to ART, or HIV-1 RNA plasma viral load suppression; provide details on MMT services; and be published in English between 1 January 2006 until 31 December 2018.
RESULTS: Out of the 5594 identified records, 22 studies were eligible for this systematic review. Components of MMT services associated with HIV care cascade outcomes described in the studies were classified in three categories of care models: 1) standard MMT care with adequate doses, 2) standard MMT care and alongside additional medical component(s), and 3) standard MMT care, additional medical component(s) as well as informational or instrumental social support.
CONCLUSION: The few studies identified reflect a scarcity of evidence on the role of social support to increase the benefits of MMT for PWUD who are living with HIV. Further research is needed to assess the role of medical and social service components in MMT care delivery in advancing PWUD along the HIV care cascade.
METHODS: We analysed incident HIV diagnoses from 2015-2018 and mortality trends from 2016-2018 for three age groups: 1) 15-24 years; 2) 25-49 years; and 3) ≥50 years. AIDS was defined as CD4<200cells/mL. Mortality was defined as deaths per 1000 patients newly diagnosed with HIV within the same calendar year. Mortality rates were calculated for 2016, 2017, and 2018, compared to age-matched general population rates, and all-cause standardized mortality ratios (SMRs) were calculated.
RESULTS: From 2015-2018, the proportion of OPWH annually diagnosed with HIV increased from 11.2% to 14.9% (p<0.01). At the time of diagnosis, OPWH were also significantly (p<0.01) more likely to have AIDS (43.8%) than those aged 25-49 years (29.5%) and 15-24 years (13.3%). Newly diagnosed OPWH had the same-year mortality ranging from 3 to 8 times higher than age-matched groups in the Ukrainian general population.
CONCLUSIONS: These findings suggest a reassessment of HIV testing, prevention and treatment strategies in Ukraine is needed to bring OPWH into focus. OPWH are more likely to present with late-stage HIV and have higher mortality rates. Re-designing testing practices is especially crucial since OPWH are absent from targeted testing programs and are increasingly diagnosed as they present with AIDS-defining symptoms. New strategies for linkage and treatment programs should reflect the distinct needs of this target population.
METHODS: A cross-sectional online survey conducted between January and April 2019 assessed the interest in HIVST in 544 MSM in Malaysia. Participants ranked eight hypothetical HIVST service delivery program elements with varied combinations of six, two-level HIVST service delivery program attributes (cost, privacy, accuracy, kit collection site, kit type, and testing support). SPSS conjoint procedure was used to estimate the relative importance of each attribute and preference across eight possible HIVST service delivery programs.
RESULTS: Overall, 70.4% had previously tested for HIV, and of those, 64.0% had done so in the past 6 months (45.0% of all participants). Of all the participants, 25.2% reported having used HIVST previously. The acceptability for HIVST service delivery models ranged from 44.9 to 77.1%, with mean acceptability of 56.2% across the eight hypothetical HIVST distribution scenarios. The HIVST service delivery scenario with the highest acceptability had the following attributes: no cost (free), anonymity (name not required), 99-100% accuracy, home-delivered, fingerstick, and testing support using telephone hotline or texting. HIVST cost was the most important attribute (relative importance score: RIS = 19.30) associated with acceptability, followed by anonymity (RIS = 18.41), accuracy (RIS = 17.33), kit delivery (RIS = 16.99), fingerstick kit (RIS = 15.86), and support (RIS = 12.08).
CONCLUSIONS: Acceptability for HIVST in Malaysian MSM was high but differed markedly by a number of HIVST delivery scenarios and attributes. These findings could be relevant as the Malaysian Ministry of Health is in the process of developing a regulatory framework for ensuring the quality of kits, as well as policies supporting safe use while broader implementation under national AIDS programs.
METHODS: Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire.
RESULTS: Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p HIV management.
TRIAL REGISTRATION: The trial is registered with Australian New Zealand Clinical Trials Registry ( ACTRN12618001882213 ). Registered 20 November 2018.
Methods: Donated blood units were assessed for the presence or absence of HBV, HCV, and HIV using two screening method: serology and NAT. Reactive blood samples were then subjected to serological confirmatory and NAT discriminatory assays.
Results: A total of 9669 donors were recruited from September 2017 to June 2018. Among these, 36 donors were reactive either for HBV, HCV, or HIV by serological testing and eight by NAT screening. However, only 10 (three for HBV and seven for HCV) donors tested positive using serological testing and five (two for HBV and three for HCV) by NAT discriminatory assays. Note that all five NAT positive donors detected in the NAT discriminatory assays were confirmed to be serologically reactive. Therefore, the prevalence of HBV, HCV, and HIV was 0.03%, 0.1%, and 0.0%, respectively, in our donor pool.
Conclusions: Both serological and NAT screening and confirmatory assays should be used routinely to reduce the risk of infection transmission via the transfusion of blood and blood components.