Anthony D. Harries

Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa

Two-thirds of the worlds HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8 and 26% of patients die in the first year of antiretroviral treatment, with most deaths occurring in the first few months. Patients typically access antiretroviral treatment with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count less than 50 cells/μl and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by antiretroviral treatment programmes, but more fundamentally on how advanced disease is at programme enrolment and the quality of preceding healthcare. In addition to improving delivery of antiretroviral treatment and providing it free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of antiretroviral treatment. Health systems delays in antiretroviral treatment initiation must be minimized, especially in patients who present with advanced immunodeficiency.

The impact of diabetes on tuberculosis treatment outcomes: A systematic review

BackgroundMultiple studies of tuberculosis treatment have indicated that patients with diabetes mellitus may experience poor outcomes.We performed a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes.MethodsWe searched PubMed, EMBASE and the World Health Organization Regional Indexes from 1 January 1980 to 31 December 2010 and references of relevant articles for reports of observational studies that included people with diabetes treated for tuberculosis. We reviewed the full text of 742 papers and included 33 studies of which 9 reported culture conversion at two to three months, 12 reported the combined outcome of failure and death, 23 reported death, 4 reported death adjusted for age and other potential confounding factors, 5 reported relapse, and 4 reported drug resistant recurrent tuberculosis.ResultsDiabetes is associated with an increased risk of failure and death during tuberculosis treatment. Patients with diabetes have a risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI, 1.36 to 2.12). The RR of death during tuberculosis treatment among the 23 unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted for age and other potential confounding factors. Diabetes is also associated with an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find evidence for an increased risk of tuberculosis recurrence with drug resistant strains among people with diabetes. The studies assessing sputum culture conversion after two to three months of tuberculosis therapy were heterogeneous with relative risks that ranged from 0.79 to 3.25.ConclusionsDiabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring.

Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi

Objectives:Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. Design and setting:A cross-sectional analytical study set in Thyolo district, Malawi. Methods:Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. Results:A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/μl and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (χ2 for trend = 96.1, P ≤ 0.001) and decreasing CD4 cell counts (χ2 for trend = 72.4, P ≤ 0.001). Individuals who were severely malnourished [body mass index (BMI) < 16.0 kg/m2] had a six times higher risk of dying in the first 3 months than those with a normal nutritional status. Conclusions:Among individuals starting ART, the BMI and clinical staging could be important screening tools for use to identify and target individuals who, despite ART, are still at a high risk of early death.

Preventing antiretroviral anarchy in sub-Saharan Africa

Combination antiretroviral therapy has dramatically improved the survival of patients living with HIV and AIDS in industrialised countries of the world. Despite this enormous benefit, there are some major problems and obstacles to be overcome.(1) Treatment of HIV-infection is likely to be lifelong.(2) Unfortunately, many HIV-infected individuals cannot tolerate the toxic effects of the drugs, or have difficulty complying with treatment which involves large numbers of pills and complicated dosing schedules. Poor adherence to treatment leads to the emergence of drug-resistant viral strains that need new combinations of drugs or new drugs altogether.

Scaling up interventions to achieve global tuberculosis control: progress and new developments

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination.

The HIV-associated tuberculosis epidemic-when will we act?

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.

Prevention of mother-to-child transmission of HIV and the health-related Millennium Development Goals: time for a public health approach

This article focuses on prevention of mother-to-child transmission (PMTCT) of HIV particularly in Malawi and discusses how the country is preparing to revise its policies for PMTCT of HIV and for antiretroviral therapy (ART) in response to WHOs 2010 guidelines. The authors propose offering all HIV-infected pregnant women lifelong ART which they see as a more feasible alternative to WHOs guidelines in addition to being more ethical. The article also describes the various benefits of their proposed plan and estimates the results and costs associated.

Moderate to severe malnutrition in patients with tuberculosis is a risk factor associated with early death

A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi to determine (i) the prevalence of malnutrition on admission and (ii) the association between malnutrition and early mortality (defined as death within the first 4 weeks of treatment). There were 1181 patients with TB (576 men and 605 women), whose overall rate of infection with human immunodeficiency virus (HIV) was 80%. 673 TB patients (57%) were malnourished on admission (body mass index [BMI] < 18.5 kg/m2). There were 259 patients (22%) with mild malnutrition (BMI 17.0-18.4 kg/m2), 168 (14%) with moderate malnutrition (BMI 16.0-16.9 kg/m2) and 246 (21%) with severe malnutrition (BMI < 15.9 kg/m2). 95 patients (8%) died during the first 4 weeks. Significant risk factors for early mortality included increasing degrees of malnutrition, age > 35 years, and HIV seropositivity. Among all the 1181 patients, 10.9% of the 414 patients with moderate to severe malnutrition died in the first 4 weeks compared with 6.5% of the 767 patients with normal to mild malnutrition (odds ratio 1.8, 95% confidence interval 1.1-2.7). In patients with TB, BMI < 17.0 kg/m2 is associated with an increased risk of early death.

Providing universal access to antiretroviral therapy in Thyolo, Malawi through task shifting and decentralization of HIV/AIDS care.

Objective  To describe how district‐wide access to HIV/AIDS care was achieved and maintained in Thyolo District, Malawi.