Severe Recurrent Bacterial Pneumonia Among Children Living With HIV.

BACKGROUND: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV. METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression. RESULTS: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018). CONCLUSIONS: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.

Viral hepatitis and the cascade of care among people living with HIV in the Asia-Pacific.

BACKGROUND: Although the prevalence and mortality of hepatitis is high in the Asia-Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). METHODS: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD-LITE) cohort, on ART, and with follow-up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co-infection if they ever tested positive for HCV antibody (anti-HCV) or HBV surface antigen (HBsAg), respectively. RESULTS: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti-HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti-HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. CONCLUSION: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment.

A scoping review of HIV epidemiologic, sociocultural and programmatic studies related to transgender women and men who have sex with men in Cambodia, 1999-2019.

BACKGROUND: Cambodia is widely credited for its successful HIV epidemic control. However, in recent years there have been signs of increasing HIV prevalence among men who have sex with men (MSM) and transgender women (TGW). This paper reviews HIV epidemiological, social science and HIV program implementation studies conducted over the past 20 years to explore possible reasons for the rising HIV prevalence among these groups and to formulate recommendations for improved policies, HIV programmatic interventions and further research. METHODS: For this scoping review, we searched the PubMed and Google Scholar databases for scientific publications related to HIV and MSM and TGW in Cambodia published since 1999. From each of the returned citations we subsequently studied reference lists to find additional data sources. We also searched websites for reports commissioned by national and international governmental and non-governmental organizations. RESULTS: Twenty-seven relevant studies and papers were found and reviewed; most were epidemiological in nature. Recent epidemiological studies and reports show an increase in HIV prevalence among Cambodian MSM and TGW. The epidemiology of HIV infection in these groups has been relatively well-described and analyzed. While initially MSM and TGW were grouped together, in more recent years they have been studied in their own right, recognizing their specific HIV and other prevention needs. Few studies were found investigating Cambodian same-sex cultures and social and cultural contexts in which HIV transmission among MSM and TGW occurs. A few evaluation studies were found, but it remains unknown how effective current HIV service implementation modalities are, or how successful strategies to increase access to essential HIV prevention, testing and treatment services have been employed for MSM and TGW in Cambodia. CONCLUSIONS: Research about Cambodian MSM and TGW in the context of HIV primarily concerns bio-behavioral knowledge generation. Cambodia is unlikely to achieve control of the HIV epidemic among MSM and TGW without doing better in-depth social science research on its multiple sexual- and gender minority cultures, and without understanding what differentiated implementation modalities, strategies and approaches are most effective to address HIV among its increasingly diverse MSM and TGW populations.

HIV-related enacted stigma and increase frequency of depressive symptoms among Thai and Cambodian adolescents and young adults with perinatal HIV.

HIV-related enacted stigma and social problems may increase risk for depression and/or behavioral problems among adolescents and young adults with perinatal HIV(AYA-PHIV), yet few studies have explored stigma in AYA-PHIV residing in low-to-middle income regions, including Southeast Asia. We assessed HIV-related enacted stigma and social problems in AYA-PHIV who participated in the RESILIENCE study (clinicaltrials.gov identification: U19AI53741) in Thailand and Cambodia using specific questions during structured in-person interviews. Depression was measured by the Child Depression Inventory for children <15 years, or the Center for Epidemiologic Studies Depression Scales for youth ≥15 years); behavioral problems were measured by the Child Behavior Checklist (CBCL-caregiver report). Among 195 AYA-PHIV (median age 16.9 years), 25.6% reported a lifetime experience of enacted stigma, while 10.8% experienced social problems due to HIV infection. The frequency of depressive symptoms was nearly two-fold higher among AYA-PHIV with compared to those without HIV-related enacted stigma (34.7% vs. 16.0%, p = 0.005). Caregiver-reported behavioral problems were detected in 14.6% of all AYA-PHIV, with no differences between those with and without HIV-related enacted stigma. Low household income and caregiver mental health problems were independent risk factors for depressive symptoms; HIV-related enacted stigma was also associated with increased risk, warranting targeted services to support AYA-PHIV.

Initial success from a public health approach to hepatitis C testing, treatment and cure in seven countries: the road to elimination.

With political will, modest financial investment and effective technical assistance, public sector hepatitis C virus (HCV) programmes can be established in low- and middle-income countries as a first step towards elimination. Seven countries, with support from the Clinton Health Access Initiative (CHAI) and partners, have expanded access to HCV treatment by combining programme simplification with market shaping to reduce commodity prices. CHAI has supported a multipronged approach to HCV programme launch in Cambodia, India, Indonesia, Myanmar, Nigeria, Rwanda and Vietnam including pricing negotiations with suppliers, policy development, fast-track registrations of quality-assured generics, financing advocacy and strengthened service delivery. Governments are leading programme implementation, leveraging HIV programme infrastructure/financing and focusing on higher-HCV prevalence populations like people living with HIV, people who inject drugs and prisoners. This manuscript aims to describe programme structure and strategies, highlight current commodity costs and outline testing and treatment volumes across these countries. Across countries, commodity costs have fallen from >US$100 per diagnostic test and US$750-US$900 per 12-week pan-genotypic direct-acting antiviral regimen to as low as US$80 per-cure commodity package, including WHO-prequalified generic drugs (sofosbuvir + daclatasvir). As of December 2019, 5900+ healthcare workers were trained, 2 209 209 patients were screened, and 120 522 patients initiated treatment. The cure (SVR12) rate was >90%, including at lower-tier facilities. Programmes are successfully implementing simplified, decentralised public health approaches. Combined with political will and affordable pricing, these efforts can translate into commitments to achieve global targets. However, to achieve elimination, additional investment in scale-up is required.

Trajectory Analysis of Cognitive Outcomes in Children With Perinatal HIV.

BACKGROUND: Children with perinatal HIV (pHIV) may display distinct long-term cognitive phenotypes. We used group-based trajectory modeling to identify clusters of children with pHIV after similar developmental trajectories and predictors of belonging to select cognitive trajectory groups. METHODS: Participants included children, 4-17 years of age, with pHIV in Thailand and Cambodia. Cognitive measures included translated versions of Intelligence Quotient tests, Color Trails Tests and Beery-Buktenica Developmental Test of Visual-Motor Integration conducted semiannually over 3-6 years. The best fit of trajectory groups was determined using maximum likelihood estimation. Multivariate logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group. RESULTS: Group-based trajectory analyses revealed a 3-cluster classification for each cognitive test, labeled as high, medium and low scoring groups. Most trajectory group scores remained stable across age. Verbal IQ declined in all 3 trajectory groups and the high scoring group for Children's Color Trails Test 1 and 2 showed an increase in scores across age. Children in the lowest scoring trajectory group were more likely to present at an older age and report lower household income. CONCLUSIONS: Group-based trajectory modeling succinctly classifies cohort heterogeneity in cognitive outcomes in pHIV. Most trajectories remained stable across age suggesting that cognitive potential is likely determined at an early age with the exception of a small subgroup of children who displayed developmental gains in select cognitive domains and may represent those with better cognitive reserve. Poverty and longer duration of untreated HIV may predispose children with pHIV to suboptimal cognitive development.

Effect of Macrolide Prophylactic Therapy on AIDS-Defining Conditions and HIV-Associated Mortality.

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.

HIV viral suppression in TREAT Asia HIV Observational Database enrolled adults on antiretroviral therapy at the Social Health Clinic, the National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia.

BACKGROUND: The Social Health Clinic at the National Center for HIV/AIDS, Dermatology & STDs (SHC-NCHADS) in Phnom Penh is a major provider of antiretroviral therapy (ART) in Cambodia. However, patient access to viral load monitoring is uncommon. We conducted a cross-sectional evaluation of HIV viral load in SHC-NCHADS patients on ART to determine the proportion experiencing virological failure and to identify factors associated with virological failure in this population. METHODS: Patients who had been using their current first- or second-line ART regimen for ≥6 months were eligible. Virological failure was defined as a viral load >1,000 copies/ml, death, lost-to-follow-up or the absence of viral load testing despite presenting for care. Factors associated with virological failure were evaluated using logistic regression. RESULTS: Overall, 463 patients (53.1% male, median age 42.1 years) were included in the investigation. At the time of current regimen initiation, median CD4+ T-cell count was 101 cells/mm3 and 89.0% of patients had experienced a WHO stage III/IV event. At the time of testing/last clinic visit, 28 (6.0%) patients met our definition of virological failure. Median viral load among those failing was 9,633 copies/ml. Shorter time on current ART regimen, low CD4+ T-cell count at the time of viral load testing/last clinic visit and a record of suboptimal adherence were the strongest predictors of virological failure. CONCLUSIONS: This work demonstrates the high rate of viral suppression being achieved by the treatment programme at SHC-NCHADS and the need for future work to phase-in routine viral load monitoring in Cambodia.

Changes in STI services following a community based STI-intervention project in Cambodia.

The aim of this study was to assess changes in sexually transmitted infections (STI) related care following a STI project with a particular focus on registered brothel-based (direct) female sex workers (DFSWs) in four border provinces of Cambodia. A survey of health care facilities providing STI care was undertaken and the results compared with a baseline survey done two years previously. The main components of the project were: renovation of the STI clinics, STI training, formation of mobile teams, provision of STI drugs, and the introduction of basic laboratory tests at STI clinics. Interviews were held with health care providers and STI patients and a manual check was made of the STI register and special forms for DFSWs. Clinical management of STI cases was assessed for DFSWs, women with vaginal discharge and men with urethral discharge. Advice given to clients about condom use, partner notification and STI education was assessed and availability of STI drugs was reviewed. STI clinic attendance by DFSWs each month increased from 72% (296/412) to 93% (459/496). The proportion of DFSWs diagnosed with presumed STIs decreased from 86.5% (256/296) to 25.5% (117/459) and cervicitis from 32.8% (135/412) to 12.6% (58/459). The percentage of men attending STI clinics decreased from 26.9% (251/933) to 9.4% (102/1,080). The proportion of presumed STI cases/all cases attending health centers decreased from 7.0% (934/13,177) to 4.3% (739/17,224). The introduction of laboratory tests coincided with a marked reduction in DFSWs diagnosed with cervicitis. Further validation studies are required to determine whether this reduction was accompanied by a real decrease in gonorrhea and chlamydia.

High prevalence of HIV and sexually transmitted infections among indirect sex workers in Cambodia.

OBJECTIVES: The goal of this study was to assess the baseline prevalence of and risk factors for HIV and other sexually transmitted infections (STIs) among beer girls enrolled in a behavioral intervention in Battambang, Cambodia. METHODS: Ninety-two of 114 women participated in baseline interviewing, HIV/STI testing, and STI treatment. Blood specimens were tested for syphilis and HIV infection. Self-administered vaginal swabs were tested for trichomonas, bacterial vaginosis (BV), gonorrhea, and chlamydia infections. RESULTS: HIV prevalence was 26%. STI prevalences were: 14% chlamydia, 12% trichomonas, 3% gonorrhea, and 0% syphilis. The prevalence of BV was 43%. A history of sex work was reported by 82%. Consistent condom use with clients was reported by 39%. Increased number of partners and symptoms of STI were significantly associated with HIV infection. DISCUSSION: These data suggest high sexual risk among beer girls in Cambodia. Targeted and frequent HIV and STI interventions are urgently needed in this population.

Current HIV/AIDS/STI epidemic: intervention programs in Cambodia, 1993-2003.

In the past decade, Cambodia has been experiencing the most serious HIV/AIDS epidemic in Southeast Asia. With full support from the top policy makers, good leadership in program management, and the commitment of the public health program officers, the HIV/AIDS prevention and care program in Cambodia has been successful, despite its resource constraints. Available data from surveillance and other studies in Cambodia indicate a downward trend in HIV prevalence and incidence among high-risk groups, an increase in condom use among commercial sex workers and their clients, and a declining trend of sexually transmitted infections. Although these findings reflect the success of programs to prevent transmission, the incidence of HIV infections is still high in high-risk populations, and transmission among the general population continues. Cambodia therefore needs to increase its efforts to reduce transmission. More research and prevention programs should focus on the vulnerable populations. HIV/AIDS modeling indicates that Cambodia needs to prepare for increasingly large numbers of AIDS patients who will require expensive medical care.