Accounting for outcomes among those lost to follow-up yields a more informative assessment of retention. Structural barriers contribute most to silent transfers, whereas psychological and social barriers tend to result in longer-term care discontinuation.
Background Mortality after initiation of antiretroviral treatment (ART) among HIV-infected patients in resource limited settings is a critical measure of the effectiveness and comparative effectiveness of the global public health response. Unknown outcomes due to high loss to follow-up (LTFU) preclude accurate accounting of deaths and limit our understanding of effectiveness. Methods We evaluated in HIV-infected adults on ART in 14 clinics in five settings in Kenya, Uganda and Tanzania using a sampling-based approach in which we intensively traced a random sample of lost patients (> 90 days late for last scheduled visit) and incorporated their vital status outcomes into analyses of the entire clinic population through probability-weighted survival analyses. Findings We followed 34,277 adults on ART from Mbarara and Kampala, Uganda; Eldoret and Kisumu, Kenya; and Morogoro, Tanzania. The median age was 35 years, 34% were men, and median pre-therapy CD4 count was 154 cells/μl. Overall 5,780 (17%) were LTFU, 991 (17%) were randomly selected for tracing and vital status was ascertained in 860 of 991 (87%). Incorporating outcomes among the lost increased estimated 3-year mortality from 3.9% (95% CI: 3.6%-4.2%) to 12.5% (95% CI: 11.8%-13.3%). The sample-corrected, unadjusted 3-year mortality across settings ranged from 7.2% in Mbarara to 23.6% in Morogoro. After adjustment for age, sex, pre-therapy CD4 value, and WHO stage, the sample-corrected hazard ratio comparing the setting with highest vs. lowest mortality was 2.2 (95% CI: 1.5-3.4) and the risk difference for death at 3 years was 11% (95% CI: 5.0%-17.7%). Interpretation A sampling based approach is widely feasible and important for understanding mortality after starting ART. After adjustment for measured biological drivers, mortality differs substantially across settings despite delivery of a similar clinical package of treatment. Implementation research to understand the systems, community, and patient behaviors driving these differences is urgently needed.
BACKGROUND There is mounting evidence for the presence of post-acute sequelae of SARS-CoV-2 infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life. METHODS We assembled a cohort of adults with documented history of SARS-CoV-2 RNA-positivity who were ≥ 2 weeks past onset of COVID-19 symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life. RESULTS Of the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 symptomatic but not hospitalized, and 44 symptomatic and hospitalized. During the post-acute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared to pre-COVID-19. Two clusters of symptom domains were identified. CONCLUSION Many participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple sub-phenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various sub-groups of PASC.
Background HIV-associated Kaposi sarcoma (KS) is one of the most common malignancies in sub-Saharan Africa. The diagnosis is often based on clinical suspicion, without histopathologic confirmation. When biopsies are performed, the accuracy of interpretation by local pathologists is poorly understood. We assessed the accuracy of clinical suspicion and pathologic diagnosis of KS in two East African countries. Methods At two large HIV care sites in Uganda and Kenya, we evaluated consecutive biopsies performed from October 2008 to January 2013 upon HIV-infected adults with clinically suspected KS. Biopsies were interpreted by both local African pathologists and a group of U.S.-based dermatopathologists from a high volume medical center. For the purpose of this analysis, the U.S.-based dermatopathologist interpretation was used as the gold standard. Positive predictive value was used to characterize accuracy of local African clinical suspicion of KS, and concordance, sensitivity, and specificity were used to characterize accuracy of local pathologic diagnosis. Results Among 1106 biopsies, the positive predictive value of clinical suspicion of KS was 77% (95% CI: 74%-79%). When KS was not histopathologically diagnosed, clinically banal conditions were found in 35%, medically significant disorders which required different therapy in 59%, and life-threatening diseases in 6%. Concordance between African pathologists and U.S.-based dermatopathologists was 69% (95% CI: 66%-72%). Sensitivity and specificity of African pathologic diagnoses were 68% and 89%, respectively. Conclusions Among East African HIV-infected patients, we found suboptimal positive predictive value of clinical suspicion of KS and specific, but not sensitive, histopathologic interpretation. The findings call for abandonment of isolated clinical diagnosis of KS in the region as well as augmentation of local dermatopathologic services.
Objective Engagement in care is key to successful HIV treatment in resource-limited settings; yet little is known about the magnitude and determinants of reengagement among patients out of care. We assessed patient-reported reasons for not returning to clinic, identified latent variables underlying these reasons, and examined their influence on subsequent care reengagement. Design We used data from the East Africa International Epidemiologic Databases to Evaluate AIDS to identify a cohort of patients disengaged from care (>3 months late for last appointment, reporting no HIV care in preceding 3 months) (n = 430) who were interviewed about reasons why they stopped care. Among the 399 patients for whom follow-up data were available, 104 returned to clinic within a median observation time of 273 days (interquartile range: 165–325). Methods We conducted exploratory and confirmatory factor analyses (EFA, CFA) to identify latent variables underlying patient-reported reasons, then used these factors as predictors of time to clinic return in adjusted Cox regression models. Results EFA and CFA findings suggested a six-factor structure that lent coherence to the range of barriers and motivations underlying care disengagement, including poverty, transport costs, and interference with work responsibilities; health system ‘failures,’ including poor treatment by providers; fearing disclosure of HIV status; feeling healthy; and treatment fatigue/seeking spiritual alternatives to medicine. Factors related to poverty and poor treatment predicted higher rate of return to clinic, whereas the treatment fatigue factor was suggestive of a reduced rate of return. Conclusion Certain barriers to reengagement appear easier to overcome than factors such as treatment fatigue. Further research will be needed to identify the easiest, least expensive interventions to reengage patients lost to HIV care systems. Interpersonal interventions may continue to play an important role in addressing psychological barriers to retention.
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