Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV?

Objectives: HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa.

Systematic review of TST responses in people living with HIV in under-resourced settings: implications for isoniazid preventive therapy.

Background: People living with HIV (PLWH) who have positive tuberculin skin tests (TST) benefit from isoniazid preventive therapy (IPT) whereas those testing TST-negative do not. Revised World Health Organization guidelines explicitly state that assessment of TST is not a requirement for initiation of IPT. However, it is not known what proportions of patients will benefit from IPT if implemented without targeting according to TST status.

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

Introduction: 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.

Methods: We defined the different steps making up the care pathway and quantified losses at each step between acquisition of HIV infection and retention in care on antiretroviral therapy (ART).

Frailty in HIV-infected adults in South Africa.

Objectives: Some evidence suggests that HIV infection is associated with premature frailty-a syndrome typically viewed as being related to ageing. We determined the prevalence and predictors of frailty in a population of HIV-infected individuals in South Africa.

Design: Case-control study of 504 adults more than the age of 30 years, composed of 248 HIV-infected adults and 256 age- and gender-matched, frequency-matched HIV-seronegative individuals.

Cryptococcal antigen screening and preemptive therapy in patients initiating antiretroviral therapy in resource-limited settings: a proposed algorithm for clinical implementation.

HIV-associated cryptococcal meningitis (CM) is estimated to cause over half a million deaths annually in Africa. Many of these deaths are preventable. Screening patients for subclinical cryptococcal infection at the time of entry into antiretroviral therapy programs using cryptococcal antigen (CRAG) immunoassays is highly effective in identifying patients at risk of developing CM, allowing these patients to then be targeted with "preemptive" therapy to prevent the development of severe disease.

PEPFAR support for the scaling up of collaborative TB/HIV activities.

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control.

Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis.

Background: Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide.

HIV and tuberculosis--science and implementation to turn the tide and reduce deaths.

Introduction: Every year, HIV-associated tuberculosis (TB) deprives 350,000 mainly young people of productive and healthy lives.People die because TB is not diagnosed and treated in those with known HIV infection and HIV infection is not diagnosed in those with TB. Even in those in whom both HIV and TB are diagnosed and treated, this often happens far too late.

Feasibility, yield, and cost of active tuberculosis case finding linked to a mobile HIV service in Cape Town, South Africa: a cross-sectional study.

Background: The World Health Organization is currently developing guidelines on screening for tuberculosis disease to inform national screening strategies. This process is complicated by significant gaps in knowledge regarding mass screening. This study aimed to assess feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service.

Diagnostic yield of tuberculosis using sputum induction in HIV-positive patients before antiretroviral therapy.

Adults (n = 602) enrolling in a South African antiretroviral treatment clinic underwent culture-based screening for tuberculosis (TB), regardless of symptoms. For those unable to spontaneously expectorate a 'spot' sample (n = 124), sputum induction with nebulised hypertonic saline was used to obtain a first sample and also to rapidly obtain a second sample from all patients. Collection of both samples typically took 10-15 min.

Indoor social networks in a South African township: potential contribution of location to tuberculosis transmission.

Background: We hypothesized that in South Africa, with a generalized tuberculosis (TB) epidemic, TB infection is predominantly acquired indoors and transmission potential is determined by the number and duration of social contacts made in locations that are conducive to TB transmission. We therefore quantified time spent and contacts met in indoor locations and public transport by residents of a South African township with a very high TB burden.

Methods: A diary-based community social mixing survey was performed in 2010.

Diagnosis of extrapulmonary tuberculosis using the Xpert(®) MTB/RIF assay.

Evaluation of: Tortoli E, Russo C, Piersimoni C et al. Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis. Eur.

Reducing deaths from tuberculosis in antiretroviral treatment programmes in sub-Saharan Africa.

Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5 and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB.

Cytomegalovirus retinitis associated with HIV in resource-constrained settings: systematic screening and case detection.

Although cytomegalovirus (CMV) can cause a wide spectrum of multi-system disorders in HIV-infected patients, retinal disease is by far the most common clinical manifestation and may lead to blindness if untreated. We discuss the rationale for systematic case detection for CMV retinitis (CMVR) within the HIV-affected population, focusing particularly on resource-limited settings. The gold standard for detection of CMVR is indirect ophthalmoscopy performed by a trained ophthalmologist.

Clinical significance of lipoarabinomannan detection in urine using a low-cost point-of-care diagnostic assay for HIV-associated tuberculosis.

Objective: A low-cost point-of-care urine assay for lipoarabinomannan (LAM) used for screening patients prior to antiretroviral therapy (ART) rapidly diagnoses a proportion of tuberculosis (TB) cases. We determined the characteristics and outcomes of such patients.

Methods: Adults enrolling in a South African township ART clinic were systematically screened for pulmonary TB by testing paired sputum samples using microscopy, liquid culture and Xpert MTB/RIF in a centralized laboratory.

Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review.

Detection of Mycobacterium tuberculosis antigens in urine is attractive as a potential means of diagnosing tuberculosis (TB) regardless of the anatomical site of disease. The most promising candidate antigen is the cell wall lipopolysaccharide antigen lipoarabinomannan (LAM), which has been used to develop commercially available enzyme-linked immunosorbent assays. Although highly variable diagnostic accuracy has been observed in different clinical populations, it is now clear that this assay has useful sensitivity for diagnosis of HIV-associated TB in patients with advanced immunodeficiency and low CD4 cell counts.

High diagnostic yield of tuberculosis from screening urine samples from HIV-infected patients with advanced immunodeficiency using the Xpert MTB/RIF assay.

We determined the diagnostic yield of the Xpert MTB/RIF assay for tuberculosis (TB) when testing small volumes of urine from ambulatory HIV-infected patients before starting antiretroviral therapy in South Africa. Compared with a gold standard of sputum culture, the sensitivity of urine Xpert among those with CD4 cell counts of <50, 50-100, and >100 cells per microliter were 44.4%, 25.

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities.

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made.

Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community.

Background: Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community.

Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control.