Suchergebnisse

AbstractIntroductionExtrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under‐resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV‐positive adults in antiretroviral therapy (ART) programmes in low‐ and middle‐income countries (LMIC).MethodsWe collected data from HIV‐positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub‐Saharan Africa, Asia‐Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes.Results and DiscussionWe analysed 2695 HIV‐positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/μL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result.ConclusionsDiagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB.

AbstractIntroductionIdentification of persons living with human immunodeficiency virus (HIV)‐associated tuberculosis (TB) at increased risk for unfavourable TB outcomes would inform efforts to improve such outcomes. We sought to identify factors associated with a decreased risk of unfavourable TB treatment outcomes among people living with HIV‐infection (PLHIV) in low‐ and middle‐income countries (LMIC), with a specific focus on directly observed therapy (DOT) compared with self‐administered therapy (SAT) during the continuation phase of anti‐TB therapy.MethodsWe conducted a retrospective cohort study among adults diagnosed with HIV‐associated TB in Africa, Asia and the Americas from 2012 to 2013; data were collected from 2012 to 2016. Unfavourable TB treatment outcomes (death during TB treatment, and TB treatment failure or recurrence) were defined according to World Health Organization criteria. Receipt of DOT was obtained at the site level and defined as ≥5 days of DOT per week. The person administering DOT and treatment location varied by site. Lack of receipt of DOT was defined as SAT. Multivariable logistic regression estimated the adjusted odds of unfavourable TB treatment outcomes.ResultsAmong 1862 adults with HIV‐associated TB included, 252 (13.5%) had unfavourable TB outcomes (226 deaths, 26 recurrences/failures). Overall, 1825 (98%) received DOT in the intensive phase and 1617 (87%) received DOT in the continuation phase. DOT in the continuation phase was not significantly associated with unfavourable TB outcomes (aOR 1.43, 95% CI 0.86 to 2.38) compared to SAT. Body mass index (BMI) change during anti‐TB treatment (per 2 units increase, aOR 0.74, 95% CI 0.68 to 0.82) and CD4+ count at TB diagnosis (200 vs. 50 cells/µL, aOR 0.54, 95% CI 0.39 to 0.73) were both independently associated with decreased odds of unfavourable TB treatment outcomes.ConclusionsIn this large, international cohort of people living with HIV‐associated TB in LMIC who received intensive phase DOT, DOT during the continuation phase of anti‐TB therapy was not associated with a decreased odds of unfavourable TB treatment outcomes compared to SAT. Randomized trials evaluating the effect of continuation‐phase DOT on TB outcomes among PLHIV are needed.

AbstractIntroductionAdolescence and pregnancy are potential risk factors for loss to follow‐up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and site‐level factors on LTFU.MethodsWe used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site‐level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups.ResultsA total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site‐level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary‐care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67).ConclusionsOlder adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents.

AbstractIntroductionThe Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow‐up (LTFU). We therefore estimated all‐cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data.MethodsWe analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia‐Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221).ResultsObserved mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person‐years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%.ConclusionsMortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.

AbstractIntroductionDolutegravir is being scaled up globally as part of antiretroviral therapy (ART), but for people with HIV and tuberculosis co‐infection, its use is complicated by a drug–drug interaction with rifampicin requiring an additional daily dose of dolutegravir. This represents a disadvantage over efavirenz, which does not have a major drug–drug interaction with rifampicin. We sought to describe HIV clinic practices for prescribing concomitant dolutegravir and rifampicin, and characterize virologic outcomes among patients with tuberculosis co‐infection receiving dolutegravir or efavirenz.MethodsWithin the four sub‐Saharan Africa regions of the International epidemiology Databases to Evaluate AIDS consortium, we conducted a site survey (2021) and a cohort study (2015–2021). The cohort study used routine clinical data and included patients newly initiating or already receiving dolutegravir or efavirenz at the time of tuberculosis diagnosis. Patients were followed from tuberculosis diagnosis until viral suppression (<1000 copies/ml), a competing event (switching ART regimen; loss to program/death) or administrative censoring at 12 months.ResultsIn the survey, 86 of 90 (96%) HIV clinics in 18 countries reported prescribing dolutegravir to patients who were receiving rifampicin as part of tuberculosis treatment, with 77 (90%) reporting that they use twice‐daily dosing of dolutegravir, of which 74 (96%) reported having 50 mg tablets available to accommodate twice‐daily dosing. The cohort study included 3563 patients in 11 countries, with 67% newly or recently initiating ART. Among patients receiving dolutegravir (n = 465), the cumulative incidence of viral suppression was 58.9% (95% confidence interval [CI]: 54.3–63.3%), switching ART regimen was 4.1% (95% CI: 2.6–6.2%) and loss to program/death was 23.4% (95% CI: 19.7–27.4%). Patients receiving dolutegravir had improved viral suppression compared with patients receiving efavirenz who had a tuberculosis diagnosis before site dolutegravir availability (adjusted subdistribution hazard ratio [aSHR]: 1.47, 95% CI: 1.28–1.68) and after site dolutegravir availability (aSHR 1.28, 95% CI: 1.08–1.51).ConclusionsAt a programmatic level, dolutegravir was being widely prescribed in sub‐Saharan Africa for people with HIV and tuberculosis co‐infection with a dose adjustment for the drug–drug interaction with rifampicin. Despite this more complex regimen, our cohort study revealed that dolutegravir did not negatively impact viral suppression.

AbstractINTRODUCTIONData on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART).METHODSWe investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load <1000 copies/mL) were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis.RESULTSOf 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS‐defining event and death.CONCLUSIONSDespite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.