Katharina Kranzer

Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review

Objective:To characterize patient and programmatic factors associated with retention in care during the pre-antiretroviral therapy (ART) period and linkage to ART care. Design:Systematic literature review. Methods:An electronic search was conducted on MEDLINE, Global Health, Google Scholar and conference databases to identify studies reporting on predictors, barriers and facilitators of retention in care in the pre-ART period, and linkage to care at three steps: ART-eligibility assessment, pre-ART care and ART initiation. Factors associated with attrition were then divided into areas for intervention. Results:Seven hundred and sixty-eight citations were identified. Forty-two studies from 12 countries were included for review, with the majority from South Africa (16). The most commonly cited category of factors was transport costs and distance. Stigma and fear of disclosure comprised the second most commonly cited category of factors followed by staff shortages, long waiting times, fear of drug side effects, male sex, younger age and the need to take time off work. Conclusion:This review highlights the importance of investigating interventions that could reduce transport difficulties. Decentralization, task-shifting and integration of services need to be expedited to alleviate health system barriers. Patient support groups and strategic posttest counselling are essential to assist patients deal with stigma and disclosure. Moreover, well tolerated first-line drugs and treatment literacy programmes are needed to improve acceptance of ART. This review suggests a combination of interventions to retain specific groups at risk for attrition such as workplace programmes for employed patients, dedicated clinic and support programmes for men and younger individuals.

Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: A prospective study

In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnerships New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.1001063

Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub-Saharan Africa: a systematic review

Recent years have seen an increasing recognition of the need to improve access and retention in care for people living with HIV/AIDS. This review aims to quantify patients along the continuum of care in sub‐Saharan Africa and review possible interventions.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

Urine lipoarabinomannan assay for tuberculosis screening before antiretroviral therapy diagnostic yield and association with immune reconstitution disease.

Objective:To assess the utility of urine lipoarabinomannan (LAM) detection as a diagnostic screening test for tuberculosis (TB) in HIV-infected patients with advanced immunodeficiency and high prevalence of sputum smear-negative pulmonary disease. Design:Cross-sectional survey. Methods:Unselected adults enrolling for antiretroviral therapy (ART) in a South African clinic were screened for TB with two sputum samples for fluorescence microscopy and mycobacterial liquid culture. LAM was measured in urine samples using a commercially available enzyme-linked immunosorbent assay. Results:Sputum culture-positive TB was diagnosed in 58 patients (median CD4 cell count = 78 cells/μl) out of 235 patients screened (TB prevalence = 0.25). Cultures were identified as positive after a mean of 24 days (SD = 9 days). The sensitivity of sputum microscopy was just 0.14 (specificity = 1.00), whereas that of LAM in concentrated urine was 0.38 (P < 0.01; specificity = 1.00). In those with CD4 cell counts of less than 50, 50–100 and more than 150 cells/μl, the LAM assay sensitivities were 0.67, 0.41 and 0.13, respectively. Corresponding values for the combined use of the LAM assay and microscopy were 0.67, 0.53 and 0.21, respectively. Among TB patients, detectable LAM was very strongly associated with low CD4 cell counts and advanced clinical stage. All patients who developed TB immune reconstitution disease (n = 5) had detectable urinary LAM at baseline. Conclusion:The LAM assay has substantially superior sensitivity to sputum microscopy as a routine diagnostic TB screening test among patients with CD4 cell counts less than 100 cells/μl. In one half of such patients, this assay could reduce the mean time to diagnosis by approximately 3 weeks. Furthermore, detectable urinary LAM may predict the development of TB immune reconstitution disease.

Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa

Background Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART. Methodology Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis. Findings Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period. Conclusion Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.

Interventions to improve or facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART in low- and middle-income settings--a systematic review.

Several approaches have been taken to reduce pre‐antiretroviral therapy (ART) losses between HIV testing and ART initiation in low‐ and middle‐income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre‐ART care and initiation of ART in low‐ and middle‐income settings.

Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources

Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy.

Changes in programmatic outcomes during 7 years of scale-up at a community-based antiretroviral treatment service in South Africa.

Objectives:To assess sustainability of programmatic outcomes in a community-based antiretroviral therapy (ART) service in South Africa during 7 years of scale-up. Methods:Prospective cohort of treatment-naive patients aged ≥15 years enrolled between 2002 and 2008. Data were analyzed by calendar period of ART initiation using time-to-event analysis and logistic regression. Results:ART was initiated by 3162 patients (67% women; median age, 34 years) who were followed-up for a median of 2.4 years (interquartile range, 1.2-3.8). After 6 years, the cumulative probability of death and loss to follow-up (LTFU) was 37.4%. The probabilities of transfer-out to another ART service and of virological failure were 21.6% and 23.1%, respectively. Low mortality risk and excellent virological and immunological responses during the first year of ART were not associated with calendar period of ART initiation. In contrast, risk of LTFU and virological failure both increased between successive calendar periods in unadjusted and adjusted analyses. The number of patients per member of clinic staff increased markedly over time. Conclusions:Successful early outcomes (low mortality and good immunological and virological responses) were sustained between sequential calendar periods during 7 years of scale-up. In contrast, the increasing cumulative probabilities of LTFU or virological failure may reflect decreasing capacity to adequately support patients during long-term therapy as clinic caseload escalated.

Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis

Summary Intensified case finding is the regular screening for evidence of tuberculosis in people infected with HIV, at high risk of HIV, or living in congregate settings. We systematically reviewed studies of intensified case finding published between January, 1994, and April, 2009. In 78 eligible studies, the number of people with tuberculosis detected during intensified case finding varied substantially between countries and target groups of patients. Median prevalence of newly diagnosed tuberculosis was 0·7% in population-based surveys, 2·2% in contact-tracing studies, 2·3% in mines, 2·3% in programmes preventing mother-to-child transmission of HIV, 2·5% in prisons, 8·2% in medical and antiretroviral treatment clinics, and 8·5% in voluntary counselling and testing services. Metaregression analysis of studies that included only people with HIV showed that for each increment in national prevalence of tuberculosis of 100 cases per 100 000 population, intensified case finding identified an additional one case per 100 screened individuals (p=0·03). Microbiological sputum examination of all individuals without prior selection by symptom screening yielded an additional four cases per 100 individuals screened (p=0·05). Data on the use of serial screening, treatment outcomes in actively identified cases of tuberculosis, and cost-effectiveness, however, were lacking. Concerted action is needed to develop intensified case finding as an important method for control of tuberculosis.