Determinants of time to antiretroviral treatment initiation and subsequent mortality on treatment in a cohort in rural northern Malawi.

BACKGROUND: To optimise care HIV patients need to be promptly initiated on antiretroviral therapy (ART) and subsequently retained on treatment. In this study we report on the interval between enrolment and treatment initiation, and investigate subsequent attrition and mortality of patients on ART at a rural clinic in Malawi. METHODS: HIV-positive individuals were recruited to a cohort study between January 2008 and August 2011 at Chilumba Rural Hospital (CRH). Outcomes were ascertained, up to 7 years after enrolment, through follow-up and by linkage to ART registers and the Karonga Health and Demographic Surveillance System (KHDSS). Kaplan-Meier methods and Cox regression were used to examine ART initiation after enrolment, mortality after ART initiation, and attrition after ART initiation. RESULTS: Of the 617 individuals recruited, 523 initiated ART between January 2008 and January 2015. Median time from HIV testing to commencement of ART was 59 days (IQR: 10-330). By a year after enrolment 74.2 % (95 % CI 70.6-77.7 %) had initiated ART. Baseline clinical data at ART initiation and data on attrition was only available for the 438 individuals who initiated ART during active follow-up, between January 2008 and August 2011. Of these individuals, 6 were missing Ministry of Health numbers, leaving 432 included in analyses of attrition and mortality. At 4 years after ART initiation 71.3 % (95 % CI 65.7-76.2 %) of these patients were retained on treatment at the CRH and 17.2 % (95 % CI 13.8-21.4 %) had died. Participants who had a lower CD4 count at enrolment (≤350 cells/µl), enrolled in 2008, or tested for HIV at the CRH rather than through serosurveys, initiated treatment faster. Once on treatment, mortality rates were higher in patients who were HIV tested at the CRH, male, older (≥35 years), missing a CD4 count, or underweight (BMI < 18.5) at ART initiation. CONCLUSIONS: Through linkage to the KHDSS and ART registers it was possible to continue follow-up beyond the end of the initial cohort study. Annual mortality after ART initiation remained considerable over a period of 4 years. Greater access to HIV and CD4 testing alongside initiation at higher CD4 counts, as planned in the test and treat strategy, could reduce this mortality.

Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi.

BACKGROUND: The emerging burden of cardiovascular disease and diabetes in sub-Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed. RESULTS: Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors. CONCLUSIONS: It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males.

Mortality trends in the era of antiretroviral therapy: evidence from the Network for Analysing Longitudinal Population based HIV/AIDS data on Africa (ALPHA).

BACKGROUND: The rollout of antiretroviral therapy (ART) is one of the largest public health interventions in Eastern and Southern Africa of recent years. Its impact is well described in clinical cohort studies, but population-based evidence is rare. METHODS: We use data from seven demographic surveillance sites that also conduct community-based HIV testing and collect information on the uptake of HIV services. We present crude death rates of adults (aged 15-64) for the period 2000-2011 by sex, HIV status, and treatment status. Parametric survival models are used to estimate age-adjusted trends in the mortality rates of people living with HIV (PLHIV) before and after the introduction of ART. RESULTS: The pooled ALPHA Network dataset contains 2.4 million person-years of follow-up time, and 39114 deaths (6893 to PLHIV). The mortality rates of PLHIV have been relatively static before the availability of ART. Mortality declined rapidly thereafter, with typical declines between 10 and 20% per annum. Compared with the pre-ART era, the total decline in mortality rates of PLHIV exceeds 58% in all study sites with available data, and amounts to 84% for women in Masaka (Uganda). Mortality declines have been larger for women than for men; a result that is statistically significant in five sites. Apart from the early phase of treatment scale up, when the mortality of PLHIV on ART was often very high, mortality declines have been observed in PLHIV both on and off ART. CONCLUSION: The expansion of treatment has had a large and pervasive effect on adult mortality. Mortality declines have been more pronounced for women, a factor that is often attributed to women's greater engagement with HIV services. Improvements in the timing of ART initiation have contributed to mortality reductions in PLHIV on ART, but also among those who have not (yet) started treatment because they are increasingly selected for early stage disease.

Use of antenatal clinic surveillance to assess the effect of sexual behavior on HIV prevalence in young women in Karonga district, Malawi.

BACKGROUND: Antenatal clinic (ANC) surveillance is the primary source of HIV prevalence estimates in low-resource settings. In younger women, prevalence approximates incidence. Sexual behavior monitoring to explain HIV distribution and trends is seldom attempted in ANC surveys. We explore the use of marital history in ANC surveillance as a proxy for sexual behavior. METHODS: Five ANC clinics in a rural African district participated in surveillance from 1999 to 2004. Unlinked anonymous HIV testing and marital history interviews (including age at first sex and socioeconomic variables) were conducted. Data on women aged <25 years were analyzed. RESULTS: Inferred sexual exposure before marriage and after first marriage increased the adjusted odds of infection with HIV by more than 0.1 for each year of exposure. Increasing years within a first marriage did not increase HIV risk. After adjusting for age, women in more recent birth cohorts were less likely to be infected. CONCLUSIONS: Marital status is useful behavioral information and can be collected in ANC surveys. Exposure in an ongoing first marriage did not increase the odds of infection with HIV in this age group. HIV prevalence decreased over time in young women. ANC surveillance programs should develop proxy sexual behavior questions, particularly in younger women.