Implications of differentiated care for successful ART scale-up in a concentrated HIV epidemic in Yangon, Myanmar.

INTRODUCTION: National AIDS Programme in Myanmar has made significant progress in scaling up antiretroviral treatment (ART) services and recognizes the importance of differentiated care for people living with HIV. Indeed, long centred around the hospital and reliant on physicians, the country's HIV response is undergoing a process of successful decentralization with HIV care increasingly being integrated into other health services as part of a systematic effort to expand access to HIV treatment. This study describes implementation of differentiated care in Médecins Sans Frontières (MSF)-supported programmes and reports its outcomes. METHODS: A descriptive cohort analysis of adult patients on antiretroviral treatment was performed. We assessed stability of patients as of 31 December 2014 and introduced an intervention of reduced frequency of physicians' consultations for stable patients, and fast tract ART refills. We measured a number of saved physician's visits as the result of this intervention. Main outcomes, remained under care, death, lost to follow up, treatment failure, were assessed on 31 December 2015 and reported as rates for different stable groups. RESULTS: On 31 December 2014, our programme counted 16, 272 adult patients enrolled in HIV care, of whom 80.34% were stable. The model allowed for an increase in the average number of patients one medical team could care for - from 745 patients in 2011 to 1, 627 in 2014 - and, thus, a reduction in the number of teams needed. An assessment of stable patients enrolled on ART one year after the implementation of the new model revealed excellent outcomes, aggregated for stable patients as 98.7% remaining in care, 0.4% dead, 0.8% lost to follow-up, 0.8% clinical treatment failure and 5.8% with immunological treatment failure. CONCLUSIONS: Implementation of a differentiated model reduced the number of visits between stable clients and physicians, reduced the medical resources required for treatment and enabled integrated treatment of the main co-morbidities. We hope that these findings will encourage other stakeholders to implement innovative models of HIV care in Myanmar, further expediting the scale up of ART services, the decentralization of treatment and the integration of care for the main HIV co-morbidities in this context.

embCAB sequence variation among ethambutol-resistant Mycobacterium tuberculosis isolates without embB306 mutation.

OBJECTIVES: Mechanisms of resistance to ethambutol in Mycobacterium tuberculosis remain inadequately described. Although there is mounting evidence that mutations of codon 306 in embB play a key role, a significant number of phenotypically ethambutol-resistant strains do not carry mutations in this codon. Here, other mutations in the embCAB operon are suggested to be involved in resistance development. METHODS: The entire embCAB operon ( approximately 10 kb) was analysed in 34 phenotypically ethambutol-resistant M. tuberculosis strains without mutations in embB306 and in 12 ethambutol-susceptible strains. Furthermore, 106 control strains were investigated for the presence of particular mutations only. RESULTS: Overall, 18 non-synonymous mutations in 15 distinct codons of the embCAB operon were identified in ethambutol-resistant strains but not in ethambutol-susceptible isolates. The majority occurred in the embB gene (10 distinct codons), in a 570 bp region also encompassing embB306. Mutations in embC and embA were found rarely and in most cases in combination with polymorphisms in embB. One synonymous mutation (embA 228 bp) and two non-synonymous mutations (embCVal981Leu and embCArg738Gln) were found in ethambutol-susceptible strains as well as resistant strains and were confirmed to represent phylogenetic markers for strains of the Beijing, Haarlem and Delhi/CAS genotypes, respectively. CONCLUSIONS: Besides mutations in embB306, mutations in embB406 and embB497 were confirmed as hot spots for genomic variation in ethambutol-resistant clinical isolates. Of all resistant strains 70.6% carry a mutation in a relatively short region in embB, which therefore represents a promising target for inclusion in molecular assays for rapid detection of ethambutol resistance.

Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment.

The rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.