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: Introduction: Lifelong antiretroviral therapy (ART) improves health outcomes for HIV‐positive individuals, but is jeopardized by irregular clinic attendance and hence poor adherence. Loss to follow‐up (LTFU) is typically defined retrospectively but this may lead to biased inferences. We assessed incidence of and factors associated with LTFU, prospectively and accounting for recurrent LTFU episodes, in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) of HIV‐positive persons in rural Tanzania. Methods: We included adults (≥15 years) enrolled in 2005 to 2016, regardless of ART status, with follow‐up through April 2017. LTFU was defined as >60 days late for a scheduled appointment. Participants could experience multiple LTFU episodes. We performed analyses based on the first (prospective) and last (retrospective) events observed during follow‐up, and accounting for recurrent LTFU episodes. Time to LTFU was estimated using cumulative incidence functions. We assessed factors associated with LTFU using cause‐specific proportional hazards, marginal means/rates, and Prentice, Williams and Peterson models. Results: Among 8087 participants (65% female, 60% aged ≥35 years, 42% WHO stage 3/4, and 47% CD4 count Conclusions: LTFU episodes were common and prompt tracing efforts are urgently needed. We identified socio‐demographic and clinical characteristics associated with LTFU that can be used to target tracing efforts and to help inform the design of appropriate interventions. Incidence of and risk factors for LTFU differed based on the LTFU definition applied, highlighting the importance of appropriately accounting for recurrent LTFU episodes. We recommend using a prospective definition of LTFU combined with recurrent event analyses in cohorts where repeated interruptions in care are common., Introduction Lifelong antiretroviral therapy (ART) is crucial to optimize health outcomes for people living with HIV. Retention in care is a critical component to reaching the second and third UNAIDS [...]

Introduction: Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory. Methods: In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL < 1000 copies/mL) or unsuppressed (HVL ≥ 1000 copies/mL). We described the proportion of PLHIV with unsuppressed HVL and adequate measures taken as per national guidelines and outcomes among those with low-level viremia (LLV; 100–999 copies/mL). We compare TAT between on-site and referral laboratories by Wilcoxon rank sum tests. Results: From 2017 to 2020, among 4,454 PLHIV, 4,238 (95%) had a blood sample taken and 4,177 (99%) of those had a result. Of those, 3,683 (88%) were virally suppressed. In the 494 (12%) unsuppressed PLHIV, 425 (86%) had a follow-up HVL (102 (24%) within 4 months and 158 (37%) had virologic failure. Of these, 103 (65%) were already on second-line ART and 32/55 (58%) switched from first- to second-line ART after a median of 7.7 months (IQR 4.7–12.7). In the 371 (9%) PLHIV with LLV, 327 (88%) had a follow-up HVL. Of these, 267 (82%) resuppressed to < 100 copies/ml, 41 (13%) had persistent LLV and 19 (6%) had unsuppressed HVL. The median TAT for return of HVL results was 21 days (IQR 13–39) at the on-site versus 59 days (IQR 27–99) at the referral laboratory (p < 0.001) with PLHIV receiving the HVL results after a median of 91 days (IQR 36–94; similar for both laboratories). Conclusion: Robust HVL monitoring is achievable in remote resource-limited settings. More focus is needed on care models for PLHIV with high viral loads to timely address results from routine HVL monitoring. [ABSTRACT FROM AUTHOR]

Objectives: Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow‐up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania. Methods: This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow‐up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time‐dependent failed pillbox return updated at every visit and LTFU using Kaplan–Meier estimation and Cox models. Results: Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7–46.2]. During a median follow‐up of 33.1 months (IQR: 17.5–52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8–33.2% vs. 19.4%, 95% CI: 17.4–21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46–1.90; p < 0.001)]. Conclusions: Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU. [ABSTRACT FROM AUTHOR]

Objectives: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub‐Saharan African countries. As a result, the rates of comorbidities and use of co‐medications among people living with HIV are increasing, necessitating a sound understanding of drug–drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting. Methods: We included consenting HIV‐positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using www.hiv-druginteractions.org as red (contra‐indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages. Results: Of 2069 participants, 1945 (94%) were prescribed at least one co‐medication during a median follow‐up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs. Conclusions: Co‐medication use was common in this rural sub‐Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians' awareness of DDIs for their recognition and management. [ABSTRACT FROM AUTHOR]

Summary: Background: Cryptococcal meningitis accounts for 15% of all AIDS mortality globally. Most cases in low‐ and middle‐income countries are treated with fluconazole monotherapy, which is associated with a high mortality. New available therapies are needed. Short‐course amphotericin B has been shown to be a safe and efficient therapeutic option. Sertraline has in vitro fungicidal activity against Cryptococcus and bi‐directional synergy with fluconazole. Methods: We conducted an open‐label clinical trial to assess the safety and efficacy of sertraline 400 mg/day and fluconazole 1200 mg/day (n = 28) vs sertraline, fluconazole and additional 5 days of amphotericin B deoxycholate 0.7‐1 mg/kg (n = 18) for cryptococcal meningitis. Results: Two‐week survival was 64% (18/28) without amphotericin and 89% (16/18) with amphotericin, and 10‐week survival was 21% (6/28) vs 61% (11/18), respectively (P = .012). The cerebrospinal fluid (CSF) Cryptococcus clearance rate was 0.264 log10 colony‐forming units (CFU)/mL of CSF/day (95% CI: 0.112‐0.416) without amphotericin and 0.473 log10 CFU/mL/day (95% CI: 0.344‐0.60) with short‐course amphotericin (P = .03). Sertraline was discontinued in one participant due to side effects. Four participants receiving amphotericin B experienced hypokalemia <2.4 mEq/L. Conclusions: Short‐course amphotericin substantially increased CSF clearance and 10‐week survival. Adjunctive sertraline improved 2‐week CSF fungal clearance but did not improve 10‐week mortality compared with published data using fluconazole 1200 mg/day monotherapy (early fungicidal activity 0.15 log10 CFU/mL/day). [ABSTRACT FROM AUTHOR]