Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIV/HCV co-infected patients in Myanmar: A prospective cohort study.

Background and Aims: In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. Methods: HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. Results: About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. Conclusion: The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.

Cost and cost-effectiveness of a real-world HCV treatment program among HIV-infected individuals in Myanmar.

INTRODUCTION: Over half of those hepatitis C virus (HCV)/HIV coinfected live in low-income and middle-income countries, and many remain undiagnosed or untreated. In 2016, Médecins Sans Frontières (MSF) established a direct-acting antiviral (DAA) treatment programme for people HCV/HIV coinfected in Myanmar. The purpose of our study was to evaluate the real-world cost and cost-effectiveness of this programme, and potential cost-effectiveness if implemented by the Ministry of Health (MoH). METHODS: Costs (patient-level microcosting) and treatment outcomes were collected from the MSF prospective cohort study in Dawei, Myanmar. A Markov model was used to assess cost-effectiveness of the programme compared with no HCV treatment from a health provider perspective. Estimated lifetime and healthcare costs (in 2017 US$) and health outcomes (in disability-adjusted life-years (DALYs)) were simulated to calculate the incremental cost-effectiveness ratio (ICER), compared with a willingness-to-pay threshold of per capita Gross Domestic Product in Myanmar ($1250). We evaluated cost-effectiveness with updated quality-assured generic DAA prices and potential cost-effectiveness of a proposed simplified treatment protocol with updated DAA prices if implemented by the MoH. RESULTS: From November 2016 to October 2017, 122 with HIV/HCV-coinfected patients were treated with DAAs (46% with cirrhosis), 96% (n=117) achieved sustained virological response. Mean treatment costs were $1229 (without cirrhosis) and $1971 (with cirrhosis), with DAA drugs being the largest contributor to cost. Compared with no treatment, the program was cost-effective (ICER $634/DALY averted); more so with updated prices for quality-assured generic DAAs (ICER $488/DALY averted). A simplified treatment protocol delivered by the MoH could be cost-effective if associated with similar outcomes (ICER $316/DALY averted). CONCLUSIONS: Using MSF programme data, the DAA treatment programme for HCV among HIV-coinfected individuals is cost-effective in Myanmar, and even more so with updated DAA prices. A simplified treatment protocol could enhance cost-effectiveness if further rollout demonstrates it is not associated with worse treatment outcomes.

Treating HIV-associated cytomegalovirus retinitis with oral valganciclovir and intra-ocular ganciclovir by primary HIV clinicians in southern Myanmar: a retrospective analysis of routinely collected data.

BACKGROUND: Cytomegalovirus retinitis (CMVR) is an opportunistic infection in HIV-infected people. Intraocular or intravenous ganciclovir was gold standard for treatment; however, oral valganciclovir replaced this in high-income countries. Low- and middle-income countries (LMIC) frequently use intraocular injection of ganciclovir (IOG) alone because of cost. METHODS: Retrospective review of all HIV-positive patients with CMVR from February 2013 to April 2017 at a Médecins Sans Frontièrs HIV clinic in Myanmar. Treatment was classified as local (IOG) or systemic (valganciclovir, or valganciclovir and IOG). The primary outcome was change in visual acuity (VA) post-treatment. Mortality was a secondary outcome. RESULTS: Fifty-three patients were included. Baseline VA was available for 103 (97%) patient eyes. Active CMVR was present in 72 (68%) eyes. Post-treatment, seven (13%) patients had improvement in VA, 30 (57%) had no change, and three (6%) deteriorated. Among patients receiving systemic therapy, four (12.5%) died, compared with five (24%) receiving local therapy (p = 0.19). CONCLUSIONS: Our results from the first introduction of valganciclovir for CMVR in LMIC show encouraging effectiveness and safety in patients with advanced HIV. We urge HIV programmes to include valganciclovir as an essential medicine, and to include CMVR screening and treatment in the package of advanced HIV care.

High levels of viral repression, malnutrition and second-line ART use in adolescents living with HIV: a mixed methods study from Myanmar.

BACKGROUND: Adolescents living with HIV/AIDS (ALHIV) are a particularly vulnerable but often overlooked group in the HIV response despite additional disease management challenges. METHODS: All ALHIV (10-19 years), on ART for ≥6 months, presenting to care at a Médecins Sans Frontières (MSF) clinic in Myanmar from January-April 2016 were eligible for the quantitative study component (clinical history, medical examination, laboratory investigation). A subset of these respondents were invited to participate in qualitative interviews. Interviews and focus groups were also conducted with other key informants (care givers, clinicians). RESULTS: Of 177 ALHIV, 56% (100) were aged 9-13 years and 77 (44%) were 14-19. 49% (86) had been orphaned by one parent, and 19% (33) by both. 59% (104) were severely underweight (BMI < 16). 47% presented with advanced HIV (WHO stage III/IV). 93% were virally supressed (< 250 copies/mL). 38 (21%) of ALHIV were on a second-line ART after first-line virological failure. Qualitative interviewing highlighted factors limiting adherence and the central role that HIV counsellors play for both ALHIV patients and caregivers. CONCLUSIONS: Our study shows good clinical, immunological, and virological outcomes for a cohort of Myanmar adolescents living with HIV, despite a majority being severely underweight, presenting with Stage III or IV illness, and the prevalence of comorbid infections (TB). Many treatment and adherence challenges were articulated in qualitative interviewing but emphasized the importance of actively engaging adolescents in their treatment. Comprehensive HIV care for this population must include routine viral load testing and social support programs.

Awareness, knowledge, and practice for hepatitis B infection in Southeast Asia: a cross-sectional study.

INTRODUCTION: The prevalence of hepatitis B virus (HBV) infection in Southeast Asia is high. Awareness and early detection are essential for timely prevention and treatment. METHODOLOGY: We examined the awareness of, knowledge about, practices and views on treatment for HBV infection in Southeast Asia. A cross-sectional survey was conducted from December 2016 to February 2017 among individuals from six nations in Southeast Asia-Myanmar, Thailand, Vietnam, Cambodia, the Philippines, and Singapore. The study population comprised healthcare and non-healthcare personnel. RESULTS: In total, 799 healthcare personnel and 1079 non-healthcare personnel completed an online survey. The prevalence of the awareness of their own HBV infection status and risk of this regionally endemic infection was 85.6% (684/799) among healthcare personnel and 54.0% (583/1079) among non-healthcare personnel. Similarly, 85.9% of healthcare personnel and 45.5% of non-healthcare personnel had good knowledge about disease transmission, complications, and the need for treatment, and 76.6% of healthcare personnel and 39.8% of non-healthcare personnel followed good HBV infection-prevention practices. Overall, 90.6% found the idea of treatment acceptable. Awareness had a significant impact on both knowledge and practice scores among both healthcare personnel and non-healthcare personnel (p < 0.01) but without statistically significant differences in treatment acceptance between the two groups (p = 0.61). CONCLUSIONS: Awareness of HBV infection was relatively low among non-healthcare personnel in Southeast Asian populations. The provision of additional hepatitis B awareness campaigns is crucial to eliminating viral hepatitis in the region.

Increased hepatitis C virus co-infection and injection drug use in HIV-infected fishermen in Myanmar.

BACKGROUND: In Southeast Asia, though fishermen are known to be a key population at high risk of HIV, little is known about their co-infection rates with Hepatitis C virus (HCV), or how illness and risk behaviors vary by occupation or type of fishermen. In Myanmar, this lack of knowledge is particularly acute, despite the fact that much of the country's border is coastline. METHODS: We conducted a retrospective analysis to assess clinical, demographic, and risk characteristics of HIV-infected, ≥15-year-old males under HIV care from 2004 to 2014. Subgroups of fishermen were categorized according to the location of fishing activities, boat ownership, and length of time at sea. Generalized linear models assessed odds of high risk behaviors, including MSM (men who have sex with men), transactional sex, injection drug use (IDU), and HCV co-infection among international, local subsistence, and national migrant fishermen. RESULTS: Of 2798 adult males who enrolled in HIV care between 2004 and 2014, 41.9% (n = 1172) were fishermen. Among these, migrants had the highest odds of engaging in risk behaviors such as sex work (Myanmar national migrants: OR 3.26 95% CI: 2.20 to 4.83), and injecting drugs (international migrants: OR 2.93, 95% CI: 1.22 to 3.87) when compared to the general male HIV clinic population. 15.9% of all fishermen reported past or current IDU (23.0% of international migrants). 22.8% of all fishermen were also co-infected with HCV, and though predictably injectors had the highest odds (OR 20.1, 95% CI: 13.7 to 29.5), even after controlling for other risk factors, fishermen retained higher odds (OR 2.37 95% CI: 1.70 to 3.32). CONCLUSIONS: HIV positive fishermen in Myanmar had higher odds of HCV co-infection. They also disproportionally injected drugs and engaged in transactional sex more than other patients. This is especially pronounced among international migrant fishermen. HIV-infected fishermen should be counseled on high risk activities, screened for HCV, and targeted by harm reduction programs.

Low Incidence of Renal Dysfunction among HIV-Infected Patients on a Tenofovir-Based First Line Antiretroviral Treatment Regimen in Myanmar.

BACKGROUND: Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction. METHODS: We used routinely collected program data on all patients aged ≥15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl < 50 ml/min/1.73 m2. We calculated incidence of renal dysfunction and used Cox regression analysis to identify associated risk factors. RESULTS: There were 1391 patients, of whom 1372 had normal renal function at baseline. Of these, 86 (6.3%) developed renal dysfunction during a median time of follow-up 1.14 years with an incidence rate of 5.4 per 100 person-years: 78 had CrCl between 30-50 ml/min/1.73 m2 and were maintained on TDF-based ART, but 5 were changed to another regimen: 4 because of CrCl <30 ml/min/1.73 m2. Risk factors for renal dysfunction included age ≥45 years, diagnosed diabetes, underlying renal disease, underweight and CD4 count <200 cells/mm3. There were 19 patients with baseline renal dysfunction and all continued on TDF-based ART: CrCl stayed between 30-49 ml/min/1.73 m2 in five patients while the remainder regained normal renal function. CONCLUSIONS: In a resource-poor country like Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit.