Sensitivity and specificity of WHO's recommended four-symptom screening rule for tuberculosis in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: Since 2011, WHO recommends a four-symptom screening rule to exclude active tuberculosis in people living with HIV before starting tuberculosis preventive treatment (ie, absence of current cough, weight loss, night sweats, or fever). We assessed the sensitivity and specificity of the screening rule among people living with HIV based on antiretroviral therapy (ART) status and the added contribution of chest radiography. METHODS: We did a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library from Jan 1, 2011, to March 12, 2018, for studies published after the WHO issued recommendations on the use of the four-symptom screening rule. We also searched abstracts from relevant international conferences. We included studies that collected sputum or any specimens (eg, urine, blood, or fine-needle aspirates from lymph nodes) from people with HIV regardless of signs or symptoms. Case-control studies were excluded because they are prone to bias. Active tuberculosis was diagnosed with bacteriological confirmation by culture or Xpert MTB/RIF of any specimens. Two investigators extracted the data, including age, sex, and ART status. We calculated sensitivity, specificity, and 95% CI. When at least four studies were available, we estimated pooled sensitivity and specificity using random and effects bivariate models; otherwise we used univariate random-effects models. FINDINGS: Of 4615 records identified by the search, 21 were included in the review (involving 15 427 people including 1559 with active tuberculosis). 18 eligible studies were included in the final meta-analysis. Seven studies provided data on people receiving ART. The pooled sensitivity of the four-symptom screening rule was lower for 4640 people on ART (51·0%, 95% CI 28·4-73·2) than for 8664 who were ART-naive (89·4%, 83·0-93·5). Pooled specificity for those on ART was 70·7% (95% CI 47·8-86·4) and for ART-naive people was 28·1% (18·6-40·1). On the basis of data from 646 individuals in two studies, the addition of any abnormal chest radiographic findings in people on ART improved sensitivity from 52·2% (95% CI 38·0-66·0) to 84·6% (69·7-92·9) but decreased specificity from 55·5% (95% CI 51·8-59·2) to 29·8% (26·3-33·6). INTERPRETATION: Our review suggested a lower sensitivity of the WHO four-symptom screening rule among people with HIV who are on ART than in those who are ART naive. The addition of chest radiography could improve the screening rule in people living with HIV who are on ART, provided it does not pose a barrier to preventive treatment. FUNDING: None.

Long-term outcomes of a pediatric HIV treatment program in Maputo, Mozambique: a cohort study.

OBJECTIVE: To describe long-term treatment outcomes of a pediatric HIV cohort in Mozambique. DESIGN: Retrospective analysis of routine monitoring data. SETTING: Secondary health care facilities in the Chamanculo Health District of Maputo. SUBJECTS: A total of 1,335 antiretroviral treatment (ART) naïve children <15 years of age enrolled in HIV care between 2002 and 2010. INTERVENTION: HIV care, ART (since 2003), task shifting to lower cadre nurses, counseling by lay counselors, active patient tracing, nutritional support, support by a psychologist, targeted viral load testing, and switch to second-line treatment. MAIN OUTCOME MEASURES: Kaplan-Meier estimates for retention in care (RIC), CD4 cell percentage, body mass index for age z-score, and adjusted incidence rate ratios for attrition (death or loss to follow-up) as calculated by Poisson regression. RESULTS: The RIC at 6 years in the pre-ART cohort was 44% (95% confidence interval: 38-49), and the one at 8 years in the ART cohort was 70% (64-75). Risk factors for attrition included young age, low CD4 percentage, underweight, active tuberculosis, and enrollment/treatment initiation after 2006. The mean CD4 percentage increased strongly at 1 year on treatment and remained high thereafter. The body mass index for age z-score sharply increased at 1 year after treatment initiation before stabilizing at pre-ART levels thereafter. CONCLUSIONS: Good clinical and immunological treatment outcomes up to 8 years of follow-up on ART can be achieved in a context of shortage of health workers and a high level of task-shifting approach.

Factors associated with virological failure and suppression after enhanced adherence counselling, in children, adolescents and adults on antiretroviral therapy for HIV in Swaziland.

INTRODUCTION: This study explores factors associated with virological detectability, and viral re-suppression after enhanced adherence counselling, in adults and children on antiretroviral therapy (ART) in Swaziland. METHODS: This descriptive study used laboratory data from 7/5/2012 to 30/9/2013, which were linked with the national ART database to provide information on time on ART and CD4 count; information on enhanced adherence counselling was obtained from file review in health facilities. Multivariable logistic regression was used to explore the relationship between viral load, gender, age, time on ART, CD4 count and receiving (or not receiving) enhanced adherence counselling. RESULTS: From 12,063 patients undergoing routine viral load monitoring, 1941 (16%) had detectable viral loads. Children were more likely to have detectable viral loads (AOR 2.6, 95%CI 1.5-4.5), as were adolescents (AOR 3.2, 95%CI 2.2-4.8), patients with last CD4<350 cells/µl (AOR 2.2, 95%CI 1.7-2.9) or WHO Stage 3/4 disease (AOR 1.3, 95%CI 1.1-1.6), and patients on ART for longer (AOR 1.1, 95%CI 1.1-1.2). At retesting, 450 (54% of those tested) showed viral re-suppression. Children were less likely to re-suppress (AOR 0.2, 95%CI 0.1-0.7), as were adolescents (AOR 0.3, 95%CI 0.2-0.8), those with initial viral load> 1000 copies/ml (AOR 0.3, 95%CI 0.1-0.7), and those with last CD4<350 cells/µl (AOR 0.4, 95%CI 0.2-0.7). Receiving (or not receiving) enhanced adherence counselling was not associated with likelihood of re-suppression. CONCLUSIONS: Children, adolescents and those with advanced disease were most likely to have high viral loads and least likely to achieve viral suppression at retesting; receiving adherence counselling was not associated with higher likelihood of viral suppression. Although the level of viral resistance was not quantified, this study suggests the need for ART treatment support that addresses the adherence problems of younger people; and to define the elements of optimal enhanced adherence support for patients of all ages with detectable viral loads.

Outcomes of antiretroviral therapy over a 10-year period of expansion: a multicohort analysis of African and Asian HIV programs.

OBJECTIVE: Little is known about the evolution of program outcomes associated with rapid expansion of antiretroviral therapy (ART) in resource-limited settings. We describe temporal trends and assess associations with mortality and loss to follow-up (LTFU) in HIV cohorts from 8 countries. DESIGN: Multicohort study using electronic health records. METHODS: Analysis included adults in 25 Médecins Sans Frontières-supported programs initiating ART between 2001 and 2011. Kaplan-Meier methods were used to describe time to death or LTFU and proportional hazards models to assess associations with individual and program factors. RESULTS: ART programs (n = 132,334, median age 35 years, 61% female) expanded rapidly. Whereas 36-month mortality decreased from 22% to 9% over 5 years (≤2003-2008), LTFU increased from 11% to 21%. Hazard ratios (HR) of early (0-12 months) and late (12-72 months) LTFU increased over time, from 1.09 [95% confidence interval (CI): 0.83 to 1.43] and 1.04 (95% CI: 0.84 to 1.28) in 2004 to 3.29 (95% CI: 2.42 to 4.46) and 6.86 (95% CI: 4.94 to 9.53) in 2011, compared with 2001-2003. Rate of program expansion was strongly associated with increased early and late LTFU, adjusted HR (aHR) = 2.31 (95% CI: 1.78 to 3.01) and HR = 2.29 (95% CI: 1.76 to 2.99), respectively, for ≥125 vs. 0-24 patients per month. Larger program size was associated with decreased early mortality (aHR = 0.49, 95% CI: 0.31 to 0.77 for ≥20,000 vs. <500 patients) and increased early LTFU (aHR = 1.77, 95% CI: 1.04 to 3.04 for ≥20,000 vs. <500 patients). CONCLUSIONS: As ART expands in resource-limited settings, challenges remain in improving access to ART and preventing program attrition. There is an urgent need for novel and sustainable models of care to increase long-term retention of patients.

Impact and programmatic implications of routine viral load monitoring in Swaziland.

OBJECTIVE: To assess the programmatic quality (coverage of testing, counseling, and retesting), cost, and outcomes (viral suppression, treatment decisions) of routine viral load (VL) monitoring in Swaziland. DESIGN: Retrospective cohort study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012 to March 31, 2013). RESULTS: Of 5563 patients eligible for routine VL testing monitoring in the period of study, an estimated 4767 patients (86%) underwent testing that year. Of 288 patients with detectable VL, 210 (73%) underwent enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months. Testing coverage was slightly lower in children, but coverage of retesting was similar between and age groups and sexes. Of those with a follow-up test, 126 (62%) showed viral suppression. The remaining 78 patients had World Health Organization-defined virologic failure; 41 (53%) were referred by the doctor for more adherence counseling, and 13 (15%) were changed to second-line therapy, equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four patients (32%) were transferred out, lost to follow-up, or not reviewed by doctor. The "fully loaded" cost of VL monitoring was $35 per patient-year. CONCLUSIONS: Achieving good quality VL monitoring is feasible and affordable in resource-limited settings, although close supervision is needed to ensure good coverage of testing and counseling. The low rate of switch to second-line therapy in patients with World Health Organization-defined virologic failure seems to reflect clinician suspicion of ongoing adherence problems. In our study, the main impact of routine VL monitoring was reinforcing adherence rather than increasing use of second-line therapy.

Clinical staging of HIV-related illness in Mozambique: performance of nonphysician clinicians based on direct observation of clinical care and implications for health worker training.

INTRODUCTION: In Mozambique, clinical staging may be the primary determinant of HIV/AIDS treatment decisions, and the task of staging commonly falls to nonphysician clinicians (técnicos de medicina). Two years after the first Mozambican técnicos were trained in HIV/AIDS care, the quality of their performance in clinical staging was unknown. METHODS: Expert clinicians observed 127 clinical encounters conducted by a randomly selected national sample of 44 técnicos and compared observed clinical staging decisions to World Health Organization and Mozambican national norms. They also reviewed relevant Mozambican in-service training curricula in HIV/AIDS care. RESULTS: Observers agreed with fewer than half (44.1%) of the técnicos' stage-defining diagnoses. Misclassification or misdiagnosis of 3 complaints (weight loss, fever, and diarrhea) accounted for the majority of the observed errors. Review of health worker curricula determined that observed staging errors reflected content errors and omissions in the técnicos' in-service HIV/AIDS training and constraints in local laboratory and imaging capacity. DISCUSSION: In response to these findings, the Mozambican Ministry of Health has revised the técnicos' scope of work and has developed new guidelines, curriculum materials, and training strategies to improve the quality of clinical staging and opportunistic infection diagnosis in Mozambique.