Rony Zachariah

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.

High acceptability of voluntary counselling and HIV-testing but unacceptable loss to follow up in a prevention of mother-to-child HIV transmission programme in rural Malawi: scaling-up requires a different way of acting.

Setting Thyolo District Hospital, rural Malawi.

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.

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.

Generic Fixed-Dose Combination Antiretroviral Treatment in Resource-Poor Settings: Multicentric Observational Cohort

Background:The use fixed-dose combination (FDC) is a critical tool in improving HAART. Studies on the effectiveness of combined lamivudine, stavudine and nevirapine (3TC/d4T/NVP) are scarce. Objective:To analyse 6861 patients in a large observational cohort from 21 Médecins Sans Frontieres (MSF) HIV/AIDS programmes taking 3TC/d4T/NVP, with subcohort analyses of patients at 12 and 18 months of treatment. Methods:Survival was analysed using Kaplan–Meier method and factors associated with progression to death with Cox proportional hazard ratio. Results:Median baseline CD4 cell count at initiating of FDC was 89 cells/μl [interquartile range (IQR), 33–158]. The median follow-up time was 4.1 months (IQR, 1.9–7.3). The incidence rate of death during follow-up was 14.2/100 person-years [95% confidence interval (CI), 13.8–14.5]. Estimates of survival (excluding those lost to follow-up) were 0.93 (95% CI, 92–94) at 6 months (n = 2,231) and 0.90 (95% CI, 89–91) at 12 months (n = 472). Using a Cox model, the following factors were associated with death: male gender, symptomatic infection, body mass index < 18 kg/m2 and CD4 cell count 15–50 cells/μl or < 15 cells/μl. Subcohort analysis of 655 patients after 1 year of follow-up (M12 FDC cohort) revealed that 77% remained on HAART, 91% of these still on the FDC regimen; 5% discontinued the FDC because of drug intolerance. At 18 months, 77% of the patients remained on HAART. Conclusions:Positive outcomes for d4T/3TC/NVP are reported for up to 18 months in terms of efficacy and safety.

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.

Offering integrated care for HIV/AIDS, diabetes and hypertension within chronic disease clinics in Cambodia

PROBLEM In Cambodia, care for people with HIV/AIDS (prevalence 1.9%) is expanding, but care for people with type II diabetes (prevalence 5-10%), arterial hypertension and other treatable chronic diseases remains very limited. APPROACH We describe the experience and outcomes of offering integrated care for HIV/AIDS, diabetes and hypertension within the setting of chronic disease clinics. LOCAL SETTING Chronic disease clinics were set up in the provincial referral hospitals of Siem Reap and Takeo, 2 provincial capitals in Cambodia. RELEVANT CHANGES At 24 months of care, 87.7% of all HIV/AIDS patients were alive and in active follow-up. For diabetes patients, this proportion was 71%. Of the HIV/AIDS patients, 9.3% had died and 3% were lost to follow-up, while for diabetes this included 3 (0.1%) deaths and 28.9% lost to follow-up. Of all diabetes patients who stayed more than 3 months in the cohort, 90% were still in follow-up at 24 months. LESSONS LEARNED Over the first three years, the chronic disease clinics have demonstrated the feasibility of integrating care for HIV/AIDS with non-communicable chronic diseases in Cambodia. Adherence support strategies proved to be complementary, resulting in good outcomes. Services were well accepted by patients, and this has had a positive effect on HIV/AIDS-related stigma. This experience shows how care for HIV/AIDS patients can act as an impetus to tackle other common chronic diseases.

Reasons for loss to follow-up among mothers registered in a prevention-of-mother-to-child transmission program in rural Malawi

This study was conducted to identify reasons for a high and progressive loss to follow-up among HIV-positive mothers within a prevention-of-mother-to-child HIV transmission (PMTCT) program in a rural district hospital in Malawi. Three focus group discussions were conducted among a total of 25 antenatal and post-natal mothers as well as nurse midwives (median age 39 years, range 22-55 years). The main reasons for loss to follow-up included: (1) not being prepared for HIV testing and its implications before the antenatal clinic (ANC) visit; (2) fear of stigma, discrimination, household conflict and even divorce on disclosure of HIV status; (3) lack of support from husbands who do not want to undergo HIV testing; (4) the feeling that one is obliged to rely on artificial feeding, which is associated with social and cultural taboos; (5) long waiting times at the ANC; and (6) inability to afford transport costs related to the long distances to the hospital. This study reveals a number of community- and provider-related operational and cultural barriers hindering the overall acceptability of PMTCT that need to be addressed urgently. Mothers attending antenatal services need to be better informed and supported, at both community and health-provider level.

Operational research in low-income countries: what, why, and how?

Operational research is increasingly being discussed at institutional meetings, donor forums, and scientific conferences, but limited published information exists on its role from a disease-control and programme perspective. We suggest a definition of operational research, clarify its relevance to infectious-disease control programmes, and describe some of the enabling factors and challenges for its integration into programme settings. Particularly in areas where the disease burden is high and resources and time are limited, investment in operational research and promotion of a culture of inquiry are needed so that health care can become more efficient. Thus, research capacity needs to be developed, specific resources allocated, and different stakeholders (academic institutions, national programme managers, and non-governmental organisations) brought together in promoting operational research.