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Background Loss to follow-up (LTFU) deprives HIV-exposed infants the lifesaving care required and results in exposing HIV free infants to virus requisition risk. We aimed to determine the rate of LTFU, postnatal mother-to-child HIV-transmission (MTCT) and to identify maternal factors associated with LTFU among HIV-exposed infants enrolled at Mbarara Regional Referral Hospital PMTCT clinic. Methods Study participants were infants born to HIV-positive mothers enrolled in the PMTCT clinic for HIV care at Mbarara Regional Referral Hospital. While access database in the Early Infant Diagnosis (EID) clinic provided data on infants, the open medical record system database at the ISS clinic provided that for mothers. Infants were classified as LTFU if they had not completed their follow-up schedule by 18 months of age. At 18 months, an infant is expected to receive a rapid diagnostic test before being discharged from the PMTCT clinic. Postnatal MTCT of HIV was calculated as a proportion of infants followed and tested from birth to 18 months of age. Logistic regression was used to determine possible associations between mothers’ characteristics and LTFU. In-depth interviews of mothers of LTFU infants and health workers who attend to the HIV-exposed infants were carried out to identify factors not captured in the electronic database. Results Out of 1624 infants enrolled at the clinic, 533 (33%) were dropped for lack of mother’s clinic identification number, 18 (1.1%) were either dead or transferred out. Out of 1073 infants analysed, 515 (48%) were LTFU by 18 months of age while out of the 558 who completed their follow-up schedule, 20 (3.6%) tested positive for HIV. Young age of mother, far distance to hospital and non-use of family planning were identified as outstanding factors responsible for LTFU. In addition, in-depth interviews revealed facility-level factors such as “waiting time” which would not be found in routine client databases. Conclusion This study has revealed a high rate of loss to follow up among HIV-exposed infants enrolled at Mbarara Regional Referral hospital PMTCT clinic. Young maternal age, long distance to health facility and failure to use family planning were significantly associated with LTFU. Incorporating family planning services in the ART and PMTCT clinics could reduce loss to follow-up of HIV exposed infants. Young mothers should be targeted with information on the importance of completing the EID follow-up schedule and also, their clinic identification number be gotten at each visit.

WHO recommends a 2-month optimal duration for new drug regimens for rifampicin-susceptible tuberculosis. We aimed to investigate the efficacy and safety of the 8-week regimens that were assessed as part of the TRUNCATE management strategy of the TRUNCATE-TB trial. TRUNCATE-TB was a multi-arm, multi-stage, open-label, randomised controlled trial in which participants aged 18–65 years with rifampicin-susceptible pulmonary tuberculosis were randomly assigned via a web-based system, using permuted blocks, to 24-week standard treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) or the TRUNCATE management strategy comprising initial 8-week treatment, then post-treatment monitoring and re-treatment where needed. The four 8-week regimens comprised five drugs, modified from standard treatment: high-dose rifampicin and linezolid, or high-dose rifampicin and clofazimine, or bedaquiline and linezolid, all given with isoniazid, pyrazinamide, and ethambutol; and rifapentine, linezolid, and levofloxacin, given with isoniazid and pyrazinamide. Here, we report the efficacy (proportion with unfavourable outcome; and difference from standard treatment, assessed via Bayesian methods) and safety of the 8-week regimens, assessed in the intention-to-treat population. This prespecified exploratory analysis is distinct from the previously reported 96-week outcome of the strategy in which the regimens were deployed. This trial is registered with ClinicalTrials.gov (NCT03474198). Between March 21, 2018, and March 26, 2020, 675 participants (674 in the intention-to-treat population) were enrolled and randomly assigned to the standard treatment group or one of the four 8-week regimen groups. Two 8-week regimens progressed to full enrolment. An unfavourable outcome (mainly relapse) occurred in seven (4%) of 181 participants on standard treatment; 46 (25%) of 184 on the high-dose rifampicin and linezolid-containing regimen (adjusted difference 21·0%, 95% Bayesian credible interval [BCI] 14·3–28·1); and 26 (14%) of 189 on the bedaquiline and linezolid-containing regimen (adjusted difference 9·3% [4·3–14·9]). Grade 3–4 adverse events occurred in 24 (14%) of 181 participants on standard treatment, 20 (11%) of 184 on the rifampicin-linezolid regimen, and 22 (12%) of 189 on the bedaquiline-linezolid regimen. Efficacy was worse with 8-week regimens, although the difference from standard treatment varied between regimens. Even the best 8-week regimen (bedaquiline-linezolid) should only be used as part of a management strategy involving post-treatment monitoring and re-treatment if necessary. Singapore National Medical Research Council; UK Department of Health and Social Care; UK Foreign, Commonwealth, and Development Office; UK Medical Research Council; Wellcome Trust; and UK Research and Innovation Medical Research Council.

Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development. Methods ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. Results Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls. Conclusions By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. Trial registration NCT, NCT02259127 , registered 7th October 2014; EUDRACT, 2014–002632-14, registered 18th June 2014 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES ); ISRCTN, ISRCTN91737921 , registered 4th October 2014.