Myo Minn Oo

High rate of virological failure and low rate of switching to second-line treatment among adolescents and adults living with HIV on first-line ART in Myanmar, 2005-2015.

Background The number of people living with HIV on antiretroviral treatment (ART) in Myanmar has been increasing rapidly in recent years. This study aimed to estimate rates of virological failure on first-line ART and switching to second-line ART due to treatment failure at the Integrated HIV Care program (IHC). Methods Routinely collected data of all adolescent and adult patients living with HIV who were initiated on first-line ART at IHC between 2005 and 2015 were retrospectively analyzed. The cumulative hazard of virological failure on first-line ART and switching to second-line ART were estimated. Crude and adjusted hazard ratios were calculated using the Cox regression model to identify risk factors associated with the two outcomes. Results Of 23,248 adults and adolescents, 7,888 (34%) were tested for HIV viral load. The incidence rate of virological failure among those tested was 3.2 per 100 person-years follow-up and the rate of switching to second-line ART among all patients was 1.4 per 100 person-years follow-up. Factors associated with virological failure included: being adolescent; being lost to follow-up at least once; having WHO stage 3 and 4 at ART initiation; and having taken first-line ART elsewhere before coming to IHC. Of the 1032 patients who met virological failure criteria, 762 (74%) switched to second-line ART. Conclusions We found high rates of virological failure among one third of patients in the cohort who were tested for viral load. Of those failing virologically on first-line ART, about one quarter were not switched to second-line ART. Routine viral load monitoring, especially for those identified as having a higher risk of treatment failure, should be considered in this setting to detect all patients failing on first-line ART. Strategies also need to be put in place to prevent treatment failure and to treat more of those patients who are actually failing.

Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar

SETTING Integrated HIV Care programme, Mandalay, Myanmar. OBJECTIVES To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. DESIGN Retrospective cohort study. RESULTS Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm(3) had a four times higher risk of an unsuccessful outcome. CONCLUSIONS Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV.

Patients with MDR-TB on domiciliary care in programmatic settings in Myanmar: Effect of a support package on preventing early deaths

Background The community-based MDR-TB care (CBMDR-TBC) project was implemented in 2015 by The Union in collaboration with national TB programme (NTP) in 33 townships of upper Myanmar to improve treatment outcomes among patients with MDR-TB registered under NTP. They received community-based support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each project township had a project nurse exclusively for MDR-TB and a community volunteer who provided evening directly observed therapy (in addition to morning directly observed therapy by NTP). Objectives To determine the effect of CBMDR-TBC project on death and unfavourable outcomes during the intensive phase of MDR-TB treatment. Methods In this cohort study involving record review, all patients diagnosed with MDR-TB between January 2015 and June 2016 in project townships and initiated on treatment till 31 Dec 2016 were included. CBMDR-TBC status was categorized as “receiving support” if project initiation in patient’s township was before treatment initiation, “receiving partial support” if project initiation was after treatment initiation, and “not receiving support” if project initiation was after intensive phase treatment outcome declaration. Time to event analysis (censored on 10 April 2017) and cox regression was done. Results Of 261 patients initiated on treatment, death and unfavourable outcomes were accounted for 13% and 21% among “receiving support (n = 163)”, 3% and 24% among “receiving partial support (n = 75)” and 13% and 26% among “not receiving support (n = 23)” respectively. After adjusting for other potential confounders, the association between CBMDR-TBC and unfavourable outcomes was not statistically significant. However, when compared to “not receiving support”, those “receiving support” and “receiving partial support” had 20% [aHR (0.95 CI: 0.8 (0.2–3.1)] and 90% lower hazard [aHR (0.95 CI: 0.1 (0.02–0.9)] of death, respectively. This was intriguing. Implementation of CBMDR-TBC coincided with implementation of decentralized MDR-TB centers at district level. Hence, patients that would have generally not accessed MDR-TB treatment before decentralization also started receiving treatment and were also included under CBMDR-TBC “received support” group. These patients could possibly be expected to sicker at treatment initiation than patients in other CBMDR-TBC groups. This could be the possible reason for nullifying the effect of CBMDR-TBC in “receiving support” group and therefore similar survival was found when compared to “not receiving support”. Conclusion CBMDR-TBC may prevent early deaths and has a scope for expansion to other townships of Myanmar and implications for NTPs globally. However, future studies should consider including data on extent of sickness at treatment initiation and patient level support received under CBMDR-TBC.

Early infant diagnosis of HIV in Myanmar: call for innovative interventions to improve uptake and reduce turnaround time

ABSTRACT Background: In collaboration with the national AIDS program, early infant diagnosis (EID) is implemented by Integrated HIV Care (IHC) program through its anti-retroviral therapy (ART) centers across 10 cities in five states and regions of Myanmar. Blood samples from the ART centers are sent using public transport to a centralized PCR facility. Objectives: Among HIV-exposed babies <9 months at enrolment into IHC program (2013–15), to describe the EID cascade (enrolment, sample collection for PCR, result receipt by mother, HIV diagnosis and ART initiation) and factors associated with delayed (>8 weeks of age) or no blood sample collection for EID. Methods: Retrospective cohort study involving record review. A predictive poisson regression model with robust variance estimates was fitted for risk factors of delayed or no sample collection. Results: Of 1349 babies, 523 (39%) of the babies’ mothers were on ART before pregnancy. Timely uptake of EID (<8 weeks of age) was 47% (633/1349); sample collection was delayed in 27% (367/1349) and not done in 26% (349/1349) babies. Among samples collected (n = 1000), 667 results were received by the mother; 52 (5%) were HIV-infected; among them 42 (81%) were initiated on ART. Median (IQR) turnaround time from sample collection to result receipt by mother and time to initiate ART from result receipt by mother was 7 (4,12) and 8.5 (6,16) weeks, respectively. Mothers not on ART before pregnancy and distance of ART center from PCR facility (more than 128 km) were the risk factors of delayed or no sample collection. Conclusions: Improving provision of ART to mothers (through universal ‘test and treat’) is urgently required, which has the potential to improve the timely uptake of EID as well. Interventions to reduce turnaround times, like point of care EID testing and/or systematic use of mobile technology to communicate results, are needed.

Evaluation of a tuberculosis active case finding project in peri-urban areas, Myanmar: 2014-2016

OBJECTIVES We assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). DESIGN Cross-sectional analysis of project records, township TB registers and annual TB reports. RESULTS In the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. CONCLUSIONS The yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB.

Attrition among HIV positive children enrolled under integrated HIV care programme in Myanmar: 12 years cohort analysis

ABSTRACT Background: In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program for HIV treatment and care since 2005. Objectives: To assess the: (a) attrition (death or loss-to-follow-up) rates among children (aged ≥ 18 months to < 15 years) enrolled into the programme before and after initiation of anti-retroviral therapy (ART) (pre-ART and ART periods); (b) demographic and clinical factors associated with attrition during these two periods. Methods: Children enrolled in IHC Programme and their status (death, lost to follow-up, regular follow-up or transferred out) was assessed as on 30 June 2017. Attrition rates (per 100 person-years) at pre – ART and ART periods were calculated and the association between demographic and clinical characteristics with attrition was assessed using Cox proportional hazards model. Results: Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100 person-years of follow-up (95% CI: 17–21) and ART attrition rate was 4 per 100 person-years of follow-up (95% CI: 3–4) with higher levels during the initial few months of enrolment. The 36-month retention rates during pre-ART period was 75% (95% CI: 72–78) and during ART period was 87% (95% CI: 86–88). The children ‘at enrolment’ with relatively lower levels of haemoglobin, immune deficiency, underweight for age, higher WHO clinical stages, presence of hepatitis B infection had higher hazards of attrition in both periods. Conclusion: The attrition rates are high particularly among children with relatively poorer clinical, nutritional profiles at enrolment. The study suggests the urgent need for improving adherence counselling especially during the initial few months of enrolment and early ART initiation.

Low Mother-to-Child HIV Transmission Rate But High Loss-to-Follow-Up Among Mothers and Babies in Mandalay, Myanmar; A Cohort Study

Introduction Loss-to-follow-up (LTFU) throughout the Prevention of Mother-To-Child Transmission (PMTCT) cascade remains one of the major threats to the success of PMTCT programs. In this study, we aimed to determine the mother-to-child transmission rate in a programmatic setting and to determine factors associated with LTFU among enrolled mothers and unfavorable outcomes among HIV-exposed babies which includes being HIV positive, death and LTFU. Methods A retrospective cohort study reviewing routinely collected data in an Integrated HIV care program, Mandalay, Myanmar in June 2016.LTFU means mother/infant missing appointed visit for more than three months. Results Of 678 pregnant women enrolled in PMTCT program between March 2011 and June 2014, one stillbirth and 607 live births were recorded in this cohort. Of 457 HIV-exposed babies with HIV-test recorded at the end of the intervention, nine (2%) were HIV-positive. Pregnant women’s and exposed-babies’ LTFU rate was 7 per 1000 person-years, and 10 per 1000 person-years respectively. PMTCT option B protocol was found to be significantly associate with maternal LTFU [adjusted Hazard Ratio (aHR) 95% CI: 3.52 (1.38–8.96)] when compare to mothers receiving option B+/lifelong antiretroviral therapy (ART). Weight <2.5 Kg at enrolment, receiving mixed-feeding, vaginal delivery and option B PMTCT protocol were significantly associated with unfavorable outcomes among exposed babies [aHR(95% CI): 5.40 (1.66–17.53), 5.91(1.68–20.84), 2.27 (1.22–4.22) and 2.33 (1.16–4.69) respectively]. Conclusion Mother-to-child HIV transmission rate in this public hospital-based program was lower than the 5% national target, which indicates a successful PMTCT intervention. However, a high proportion of HIV-infected mothers and exposed babies LTFU was recorded. Lifelong ART provision to HIV-positive pregnant women was shown to reduce exposed babies’ LTFU, death and transmission rate (unfavorable outcomes) in this setting. Lessons learned from this program could be used to inform policy and practice in the country, while the programmatic challenge of LTFU should be urgently addressed.

Long-term outcomes of second-line antiretroviral treatment in an adult and adolescent cohort in Myanmar

ABSTRACT Background: Myanmar has a high burden of Human Immunodeficiency Virus (HIV) and second-line antiretroviral treatment (ART) has been available since 2008 in the public health sector. However, there have been no published data about the outcomes of such patients until now. Objective: To assess the treatment and programmatic outcomes and factors associated with unfavorable outcomes (treatment failure, death and loss to follow-up from care) among people living with HIV (aged ≥ 10 years) receiving protease inhibitor-based second-line ART under the Integrated HIV Care Program in Myanmar between October 2008 and June 2015. Design: Retrospective cohort study using routinely collected program data. Results: Of 824 adults and adolescents on second-line ART, 52 patients received viral load testing and 19 patients were diagnosed with virological failure. However, their treatment was not modified. At the end of a total follow-up duration of 7 years, 88 (11%) patients died, 35 (4%) were lost to follow-up, 21 (2%) were transferred out to other health facilities and 680 (83%) were still under care. The incidence rate of unfavorable outcomes was 7.9 patients per 100 person years follow-up. Patients with a history of injecting drug use, with a history of lost to follow-up, with a higher baseline viral load and who had received didanosine and abacavir had a higher risk of unfavorable outcomes. Patients with higher baseline C4 counts, those having taken first-line ART at a private clinic, receiving ART at decentralized sites and taking zidovudine and lamivudine had a lower risk of unfavorable outcomes. Conclusions: Long-term outcomes of patients on second-line ART were relatively good in this cohort. Virological failure was relatively low, possibly because of lack of viral load testing. No patient who failed on second-line ART was switched to third-line treatment. The National HIV/AIDS Program should consider making routine viral load monitoring and third-line ART drugs available after a careful cost–benefit analysis.

Factors associated with long turnaround time for early infant diagnosis of HIV in Myanmar

ABSTRACT Background: A previous review of early infant diagnosis (EID) using polymerase chain reaction technology (PCR) under integrated HIV care (IHC) program in Myanmar revealed a low uptake of timely (within 6 to 8 weeks of babies’ age) EID and a long turnaround time (TAT) of receiving results. Objective: This study aimed to determine the proportion and factors associated with the composite outcome of a long TAT (≥7 weeks; from sample collection to receipt of result by mother) or nonreceipt of result among HIV-exposed babies whose blood samples were collected for PCR at <9 months of age under the IHC program, Myanmar (2013–15). Methods: Cohort study involving record review of routinely collected data. A predictive Poisson regression model with robust variance estimates was fitted for risk factors of long TAT or nonreceipt of result. Results: Blood samples of 1 000 babies were collected; among them, long TAT or nonreceipt of results was seen in 690 (69%), and this was more than 50% across all subgroups. Babies with a mother’s CD4 count of 100–350 cells/mm3 at enrollment [adjusted RR (0.95 confidence intervals, CI): 0.8 (0.7, 0.9)] had a 20% lower risk of long TAT or nonreceipt of results when compared with ≥350 cells/mm3. Distance between ART center and PCR facility ≥105 km [adjusted RR (0.95 CI): 1.2 (1.1, 1.4)], when compared with <105 km, was associated with 20% higher risk of long TAT or nonreceipt of results. Conclusions: The proportion of babies with long TAT or nonreceipt of result by the mother was high. Point-of-care testing for EID may reduce TAT/nonreceipt of results by the mother. Health system, laboratory, and logistic factors such as sample transportation, laboratory procedures, and result dispatching associated with long TAT should be further explored.

Alarming attrition rates among HIV-infected individuals in pre-antiretroviral therapy care in Myanmar, 2011–2014

Background High retention rates have been documented among patients receiving antiretroviral therapy (ART) in Myanmar. However, there is no information on human immunodeficiency virus (HIV)-infected individuals in care before initiation of ART (pre-ART care). We assessed attrition (loss-to-follow-up [LTFU] and death) rates among HIV-infected individuals in pre-ART care and their associated factors over a 4-year period. Design In this retrospective cohort study, we extracted routinely collected data of HIV-infected adults (>15 years old) entering pre-ART care (June 2011–June 2014) as part of an Integrated HIV Care (IHC) programme, Myanmar. Attrition rates per 100 person-years and cumulative incidence of attrition were calculated. Factors associated with attrition were examined by calculating hazard ratios (HRs). Results Of 18,037 HIV-infected adults enrolled in the IHC programme, 11,464 (63%) entered pre-ART care (60% men, mean age 37 years, median cluster of differentiation 4 (CD4) cell count 160 cells/µL). Of the 11,464 eligible participants, 3,712 (32%) underwent attrition of which 43% were due to deaths and 57% were due to LTFU. The attrition rate was 78 per 100 person-years (95% CI, 75–80). The cumulative incidence of attrition was 70% at the end of a 4-year follow-up, of which nearly 90% occurred in the first 6 months. Male sex (HR 1.5, 95% CI 1.4–1.6), WHO clinical Stage 3 and 4, CD4 count <200 cells/µL, abnormal BMI, and anaemia were statistically significant predictors of attrition. Conclusions Pre-ART care attrition among persons living with HIV in Myanmar was alarmingly high – with most attrition occurring within the first 6 months. Strategies aimed at improving early HIV diagnosis and initiation of ART are needed. Suggestions include comprehensive nutrition support and intensified monitoring to prevent pre-ART care attrition by tracking patients who do not return for pre-ART care appointments. It is high time that Myanmar moves towards a ‘test and treat’ approach and ultimately eliminates the need for pre-ART care.