Losses to follow-up after initiation of antiretroviral therapy (ART) are common in Africa and are a considerable obstacle to understanding the effectiveness of nascent treatment programs. We sought to characterize, through a sampling-based approach, reasons for and outcomes of patients who become lost to follow-up.Cohort study.We searched for and interviewed a representative sample of lost patients or close informants in the community to determine reasons for and outcomes among lost patients.Three thousand six hundred twenty-eight HIV-infected adults initiated ART between January 1, 2004 and September 30, 2007 in Mbarara, Uganda. Eight hundred twenty-nine became lost to follow-up (cumulative incidence at 1, 2, and 3 years of 16%, 30%, and 39%). We sought a representative sample of 128 lost patients in the community and ascertained vital status in 111 (87%). Top reasons for loss included lack of transportation or money and work/child care responsibilities. Among the 111 lost patients who had their vital status ascertained through tracking, 32 deaths occurred (cumulative 1-year incidence 36%); mortality was highest shortly after the last clinic visit. Lower pre-ART CD4 T-cell count, older age, low blood pressure, and a central nervous system syndrome at the last clinic visit predicted deaths. Of patients directly interviewed, 83% were in care at another clinic and 71% were still using ART.Sociostructural factors are the primary reasons for loss to follow-up. Outcomes among the lost are heterogeneous: both deaths and transfers to other clinics were common. Tracking a sample of lost patients is an efficient means for programs to understand site-specific reasons for and outcomes among patients lost to follow-up.
To evaluate the concordance between adherence estimated by self-report (in-person interview or computer-assisted self-interview), in-clinic pill counts, and pharmacy dispensation records and drug detection among participants in a placebo-controlled pre-exposure prophylaxis HIV prevention trial (iPrEx).Cross-sectional evaluation of 510 participants who had drug concentration data and matched adherence assessments from their week-24 study visit.Self-reported adherence collected through (1) interview and (2) computer-assisted self-interview surveys, (3) adherence estimated by pill count, and (4) medication possession ratio was contrasted to having a detectable level of drug concentrations [either tenofovir diphosphate (TFV-DP) or emtricitabine triphosphate (FTC-TP)], as well as to having evidence of consistent dosing (tenofovir diphosphate ≥ 16 fmol/10⁶ cells), focusing on positive predictive values, overall and by research site.Overall, self-report and pharmacy records suggested high rates of product use (over 90% adherence); however, large discrepancies between these measures and drug detection were noted, which varied considerably between sites (positive predictive values from 34% to 62%). Measures of adherence performed generally well in the US sites but had poor accuracy in other research locations. Medication possession ratio outperformed other measures but still had relatively low discrimination.The sizable discrepancy between adherence measures and drug detection in certain regions highlights the potential contribution of factors that may have incentivized efforts to seem adherent. Understanding the processes driving adherence reporting in some settings, but not others, is essential for finding effective ways to increase accuracy in measurement of product use and may generalize to promotion efforts for open-label pre-exposure prophylaxis.
Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown.Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes.Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant.Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.
Purpose: To assess the impact of voriconazole exposure on squamous cell carcinoma, invasive aspergillosis, and death in lung transplant recipients. Methods: Utilizing a cohort of all lung transplant recipients at the University of California, San Francisco (UCSF) between October 1991 and December 2012 (n=455), we used survival analysis to test whether voriconazole exposure impacted development of squamous cell carcinoma, invasive aspergillosis, and death. Voriconazole exposure was assessed as either any exposure or cumulative dose exposure as a time varying covariate. Cox regression models were built with modified Allan-Cady backwards selection adjusting for sex, age at transplant, and race kept a priori, in addition to type and year of transplant and diagnostic category to calculate the adjusted hazard ratio. Results: Any voriconazole exposure was associated with a 2-fold increased risk for developing squamous cell carcinoma (HR=2.01, p=0.004), with each additional 12 g of exposure (equivalent to 200 mg BID for 30 days) increasing the risk by 3.0% (HR=1.03, p=<0.0001). Individuals with older-age at transplant (HR=1.53, p=.03), Male sex (HR=1.49, p=.05), White race (HR=4.79, p=<0.0001), or Lung Allocation Score (LAS) Group D diagnostic category (HR=1.55, p=0.04) were the most at risk. Drug exposure was also associated with a 39% risk reduction for developing invasive aspergillosis (HR=0.61, p=0.03) and a 53% risk reduction for death (HR=0.47, p=0.00). Conclusion: Voriconazole exposure is associated with a dose-dependent increased risk for developing squamous cell carcinoma in lung transplant recipients, but also significantly decreases risk for invasive aspergillosis and death. Physicians should consider patient-specific factors that modify the risk for developing skin cancer and reducing fungal infections and death when using voriconazole in the care of lung transplant recipients.
Churdboonchart et al. ([2][1]) paint an impressive picture of the effects of Remune on CD4 cell count in HIV-infected subjects. However, as individuals who were closely involved in the study, we believe that the paper presents a misleading account of the study results and a distorted view of the
Survival rates of 609 cases of acquired immunodeficiency syndrome (AIDS) in Washington State diagnosed between 1982 and 1987 according to pre-1987 AIDS surveillance definition were analyzed. People with a primary diagnosis of Kaposi's sarcoma survived longer than those with Pneumocystis carinii pneumonia. Both groups survived longer than those with other diagnoses. Median survival increased from 11.3, to 12.5, to 20.8 months for cases diagnosed in or before 1985, during 1986, and during 1987, respectively.
Genetic studies of complex diseases must confront two statistically difficult issues simultaneously.First, in many settings, to minimize the number of individuals to be genotyped, families enriched for disease must be oversampled.Also, statistical models in family studies should allow for residual association.This association will represent unmeasured genetic and environmental factors influencing disease risk.Dealing with these features simultaneously is both compelling and challenging.Burton et al. [2000] (Am.J. Hum.Gen. 69: 1505-14) recently discussed this issue and suggested that ascertainment corrections may lead to problematic parameter estimation.We revisit the issues and examples of Burton et al. [2000] (Am.J. Hum.Genet.69: 1505-14) and present a more optimistic assessment.Estimation in this context is conceptually straightforward, but may be more problematic in practice.Specifically, we find that even slight misspecification of the random effects distribution in ascertainment-adjusted likelihood can yield severely biased parameter estimates.This result should make scientists wary when interpreting results from ascertainment-adjusted variance-component models.
Coronavirus disease-2019 (COVID-19) threatens to further worsen HIV outcomes among people experiencing homelessness. We conducted an interrupted time-series analysis of care engagement and viral suppression among unhoused individuals in the 'POP-UP' low-barrier, high-intensity HIV primary care program during COVID-19. Among 85 patients, care engagement and viral suppression did not decrease in the 5 months following implementation of San Francisco's 'shelter-in-place' ordinance. Low-barrier, in-person HIV care for homeless individuals may be important for maintaining HIV outcomes during COVID-19.
