Urine Lipoarabinomannan Testing for All HIV Patients Hospitalized in Medical Wards Identifies a Large Proportion of Patients With Tuberculosis at Risk of Death.

BACKGROUND: Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in medical wards and 6-month mortality according to LAM results. METHODS: This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination, and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest x-ray, and CD4 count were systematically requested. RESULTS: Among 387 inpatients, 54% had a CD4 <200 cells/µL, 64% had presumptive TB, and 90% had ≥1 TB symptom recorded in their medical file. LAM results were available for 99.0% of patients, microscopy for 62.8%, and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-month mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives (P = .013). In multivariable regression analyses, LAM-positive patients had a higher risk of mortality than LAM-negatives (adjusted odds ratio, 2.5; 95% CI, 1.1-5.8; P = .037). CONCLUSIONS: In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.

Feasibility of using Determine TB-LAM to diagnose tuberculosis in HIV-positive patients in programmatic conditions: a multisite study.

Background: Determine TB-LAM is a urine-based point-of-care assay for diagnosis of tuberculosis (TB). Objective: To assess the feasibility of using LAM to diagnose TB in adult HIV-positive patients in resource-limited settings. Methods: We performed a multi-centric mixed-methods cross-sectional descriptive study in the Democratic Republic of Congo, Malawi, and Mozambique. We used the study and program monitoring tools to estimate user workload, turn-around time (TAT), and proportion of patients with LAM and sputum-based results. We conducted semi-structured interviews to assess the user acceptability of the LAM. Results: The duration of the LAM testing activity per patient was 27 min (IQR 26-29); staff continued with other duties whilst waiting for the result. More patients had a LAM versus a sputum-based result: 168/213 (78.9%) vs 77/213 (36.1%), p < 0.001 in DRC; 691/695 (99.4%) vs 429/695 (61.7%), p < 0.001 in Malawi; and 646/647 (99.8%) vs 262/647 (40.5%), p < 0.001 in Mozambique. The median TAT in minutes when LAM was performed in the consultation room was 75 (IQR 45-188) in DRC, 29 (IQR 27-39) in Malawi, and 36 (IQR 35-41) in Mozambique. In comparison, the overall median TAT for sputum-based tests (smear or GeneXpert) was 2 (IQR 1-3) days. The median time to the first anti-TB drug dose for LAM-positive patients was 155 (IQR 90-504) minutes in DRC and 90 (IQR 60-117) minutes in Mozambique. The overall inter-reader agreement for the interpretation of the LAM result as positive or negative was 98.9%, kappa 0.97 (95%CI 0.96-0.99). Overall, LAM users found the test easy to perform. Major concerns were use of the reading card and the prior requirement of CD4 results before LAM testing. Conclusion: It is feasible to implement the LAM test in low resource settings. The short TAT permitted same day initiation of TB treatment for LAM-positive patients.

Retention in care among clinically stable antiretroviral therapy patients following a six-monthly clinical consultation schedule: findings from a cohort study in rural Malawi.

INTRODUCTION: Longer intervals between clinic consultations for clinically stable antiretroviral therapy (ART) patients may improve retention in care and reduce facility workload. We assessed long-term retention among clinically stable ART patients attending six-monthly clinical consultations (SMCC) with three-monthly fast-track drug refills, and estimated the number of consultations "saved" by this model of ART delivery in rural Malawi. METHODS: Stable patients (aged ≥18 years, on first-line ART ≥12 months, CD4 count ≥300 cells/mL3 , without opportunistic infections, not pregnant/breastfeeding) were eligible for SMCC, with three-monthly drug refills from community health workers. Early enrollees were those starting SMCC within six months of eligibility, while late enrollees started at least 6 months after first eligibility. Kaplan-Meier methods were used to calculate cumulative probabilities of retention, stratified by timing of their enrolment and from first six-monthly clinical consultation. Cox regression was used to measure attrition hazards from the first six-monthly clinical consultation and risk factors for attrition, accounting for the time-varying nature of their eligibility and enrolment in this model of care. RESULTS: From 2008 to 2015, 22,633 clinically stable patients from 11 facilities were eligible for SMCC for at least three months, contributing 74,264 person-years of observation, and 18,363 persons (81%) initiated this model of care. The median time from eligibility to enrolment was 12 months and the median cumulative time on SMCC was 14.5 months. Five years after first SMCC eligibility, cumulative probabilities of retention were 85.5% (95% CI: 84.0% to 86.9%) among early enrollees and 93% (95% CI: 92.8% to 94.0%) among late enrollees. The cumulative probability of retention from first SMCC was 97.0% (95% CI: 96.7% to 97.3%) and 86% (95% CI: 85% to 87%) at one and five years respectively. Among eligible patients initiating SMCC, the adjusted hazards of attrition were 2.4 (95% CI: 2.0 to 2.8) times higher during periods of SMCC discontinuation compared to periods on SMCC. Male sex, younger age, more recent SMCC eligibility and WHO Stage 3/4 conditions in the past year were also independently associated with attrition from SMCC. Approximately 26,000 consultations were "saved" during 2014. CONCLUSION: After five years, retention among patients attending SMCC was high, especially among women and older patients, and its scale-up could facilitate universal access to ART.

Hair loss induced by lopinavir-ritonavir.

A 38-year-old Caucasian woman with uncontrolled human immunodeficiency virus (HIV) infection was treated with highly active antiretroviral therapy (HAART) consisting of zidovudine, lamivudine, and nevirapine. Because her therapeutic response was inadequate, the HAART regimen was changed to abacavir, lamivudine, and lopinavir-ritonavir. Three months after this therapy was started, the patient developed progressive and notable hair loss. Her hair became fair and thin, and her appearance deteriorated considerably. Hair loss due to HAART was diagnosed. Lopinavir-ritonavir was stopped, and efavirenz was substituted; abacavir and lamivudine were continued. After 4 weeks, her hair growth substantially improved, as evidenced by rapid growth of new hair. Her general condition also improved. No relapse was observed with the new HAART regimen, and the patient's hair loss completely reversed in 8 weeks. Alopecia is a possible adverse event in HIV-infected patients treated with protease inhibitors, particularly indinavir. Our patient's severe and generalized alopecia was temporally related to the initiation and discontinuation of lopinavir-ritonavir. On the basis of the Naranjo adverse drug reaction probability scale, the adverse reaction was considered probable. Although generalized hair loss due to lopinavir-ritonavir is rare, clinicians should be aware of this potential adverse reaction of this widely used drug. If alopecia is severe or particularly distressing to the patient, the offending drug should be discontinued, and therapy with another HIV drug should be started.