Basia Zaba

Population-level effect of HIV on adult mortality and early evidence of reversal after introduction of antiretroviral therapy in Malawi

Summary Background Malawi, which has about 80 000 deaths from AIDS every year, made free antiretroviral therapy available to more than 80 000 patients between 2004 and 2006. We aimed to investigate mortality in a population before and after the introduction of free antiretroviral therapy, and therefore to assess the effects of such programmes on survival at the population level. Methods We used a demographic surveillance system to measure mortality in a population of 32 000 in northern Malawi, from August, 2002, when free antiretroviral therapy was not available in the study district, until February, 2006, 8 months after a clinic opened. Causes of death were established through verbal autopsies (retrospective interviews). Patients who registered for antiretroviral therapy at the clinic were identified and linked to the population under surveillance. Trends in mortality were analysed by age, sex, cause of death, and zone of residence. Findings Before antiretroviral therapy became available in June, 2005, mortality in adults (aged 15–59 years) was 9·8 deaths for 1000 person-years of observation (95% CI 8·9–10·9). The probability of dying between the ages of 15 and 60 years was 43% (39–49) for men and 43% (38–47) for women; 229 of 352 deaths (65·1%) were attributed to AIDS. 8 months after the clinic that provided antiretroviral therapy opened, 107 adults from the study population had accessed treatment, out of an estimated 334 in need of treatment. Overall mortality in adults had decreased by 10% from 10·2 to 8·7 deaths for 1000 person-years of observation (adjusted rate ratio 0·90, 95% CI 0·70–1·14). Mortality was reduced by 35% (adjusted rate ratio 0·65, 0·46–0·92) in adults near the main road, where mortality before antiretroviral therapy was highest (from 13·2 to 8·5 deaths per 1000 person-years of observation before and after antiretroviral therapy). Mortality in adults aged 60 years or older did not change. Interpretation Our findings of a reduction in mortality in adults aged between 15 and 59 years, with no change in those older than 60 years, suggests that deaths from AIDS were averted by the rapid scale-up of free antiretroviral therapy in rural Malawi, which led to a decline in adult mortality that was detectable at the population level. Funding Wellcome Trust and British Leprosy Relief Association.

Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy.

Objectives:To estimate survival patterns after HIV infection in adults in low and middle-income countries. Design:An analysis of pooled data from eight different studies in six countries. Methods:HIV seroconverters were included from eight studies (three population-based, two occupational, and three clinic cohorts) if they were at least 15 years of age, and had no more than 4 years between the last HIV-negative and subsequent HIV-positive test. Four strata were defined: East African cohorts; South African miners cohort; Thai cohorts; Haitian clinic cohort. Kaplan–Meier functions were used to estimate survival patterns, and Weibull distributions were used to model and extend survival estimates. Analyses examined the effect of site, age, and sex on survival. Results:From 3823 eligible seroconverters, 1079 deaths were observed in 19 671 person-years of follow-up. Survival times varied by age and by study site. Adjusting to age 25–29 years at seroconversion, the median survival was longer in South African miners: 11.6 years [95% confidence interval (CI) 9.8–13.7] and East African cohorts: 11.1 years (95% CI 8.7–14.2) than in Haiti: 8.3 years (95% CI 3.2–21.4) and Thailand: 7.5 years (95% CI 5.4–10.4). Survival was similar for men and women, after adjustment for age at seroconversion and site. Conclusion:Without antiretroviral therapy, overall survival after HIV infection in African cohorts was similar to survival in high-income countries, with a similar pattern of faster progression at older ages at seroconversion. Survival appears to be significantly worse in Thailand where other, unmeasured factors may affect progression.

The Spectrum projection package: improvements in estimating mortality, ART needs, PMTCT impact and uncertainty bounds

Background: The approach to national and global estimates of HIV/AIDS used by UNAIDS starts with estimates of adult HIV prevalence prepared from surveillance data using either the Estimation and Projection Package (EPP) or the Workbook. Time trends of prevalence are transferred to Spectrum to estimate the consequences of the HIV/AIDS epidemic, including the number of people living with HIV, new infections, AIDS deaths, AIDS orphans, treatment needs and the impact of treatment on survival. Methods: The UNAIDS Reference Group on Estimates, Modelling and Projections regularly reviews new data and information needs and recommends updates to the methodology and assumptions used in Spectrum. The latest update to Spectrum was used in the 2007 round of global estimates. Results: Several new features have been added to Spectrum in the past two years. The structure of the population was reorganised to track populations by HIV status and treatment status. Mortality estimates were improved by the adoption of new approaches to estimating non-AIDS mortality by single age, and the use of new information on survival with HIV in non-treated cohorts and on the survival of patients on antiretroviral treatment (ART). A more detailed treatment of mother-to-child transmission of HIV now provides more prophylaxis and infant feeding options. New procedures were implemented to estimate the uncertainty around each of the key outputs. Conclusions: The latest update to the Spectrum program is intended to incorporate the latest research findings and provide new outputs needed by national and international planners.

HIV and Mortality of Mothers and Children: Evidence From Cohort Studies in Uganda, Tanzania, and Malawi

Background: The steady decline in child mortality observed in most African countries through the 1960s, 1970s, and 1980s has stalled in many countries in the 1990s because of the AIDS epidemic. However, the census and household survey data that generally are used to produce estimates of child mortality do not permit precise measures of the adverse effect of HIV on child mortality. Methods: To calculate excess risks of child mortality as the result of maternal HIV status, we used pooled data from 3 longitudinal community-based studies that classified births by the mothers HIV status. We also estimated excess risks of child death caused by increased mortality among mothers. The joint effects of maternal HIV status and maternal survival were quantified using multivariate techniques in a survival analysis. Results: Our analysis shows that the excess risk of death associated with having an HIV-positive mother is 2.9 (95% confidence interval = 2.3–3.6), and this effect lasts throughout childhood. The excess risk associated with a maternal death is 3.9 (2.8–5.5) in the 2-year period centered on the mothers death, with children of both infected and uninfected mothers experiencing higher mortality risks at this time. Conclusion: HIV impacts on child mortality directly through transmission of the virus to newborns by infected mothers and indirectly through higher child mortality rates associated with a maternal death.

Estimating Incidence from Prevalence in Generalised HIV Epidemics: Methods and Validation

Background HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence. Methods and Findings Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured. Conclusions It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.

The effects of high HIV prevalence on orphanhood and living arrangements of children in Malawi, Tanzania, and South Africa

Using longitudinal data from three demographic surveillance systems (DSS) and a retrospective cohort study, we estimate levels and trends in the prevalence and incidence of orphanhood in South Africa, Tanzania, and Malawi in the period 1988–2004. The prevalence of maternal, paternal, and double orphans rose in all three populations. In South Africa—where the HIV epidemic started later, has been very severe, and has not yet stabilized—the incidence of orphanhood among children is double that of the other populations. The living arrangements of children vary considerably between the populations, particularly in relation to fathers. Patterns of marriage, migration, and adult mortality influence the living and care arrangements of orphans and non-orphans. DSS data provide new insights into the impact of adult mortality on children, challenging several widely held assumptions. For example, we find no evidence that the prevalence of child-headed households is significant or has increased in the three study areas.

Estimating the net effect of HIV on child mortality in African populations affected by generalized HIV epidemics

Summary:For a given prevalence, HIV has a relatively higher impact on child mortality when mortality from other causes is low. To project the effect of the epidemic on child mortality, it is necessary to estimate a realistic schedule of “net” age-specific mortality rates that would operate if HIV were the only cause of child death observable. We assume that this net pattern would be independent of mortality from other causes. We used African studies that measured the survival of HIV-infected children (direct data) or survival of children of HIV-infected mothers (indirect data). We developed a mathematic procedure to estimate the mortality of infected children from indirect data sources and obtained net HIV mortality patterns for each study population. The net age-specific HIV mortality pattern for infected children can be described by a double Weibull curve fitted to empiric data; this gives a functional representation of age-specific mortality rates that decline after infancy and rise in the preteens. The fitted curve that we would expect if HIV were the only effective cause of death shows 67% net survival at 1 year and 39% at 5 years. The curve also predicts 13% net survival at 10 years using constraints based on survival of infected adults.

Uptake of HIV voluntary counselling and testing services in rural Tanzania: implications for effective HIV prevention and equitable access to treatment

Objective  To describe the associations between socio‐demographic, behavioural and clinical characteristics and the use of HIV voluntary counselling and testing (VCT) services among residents in a rural ward in Tanzania.

Doubts, denial and divine intervention: understanding delayed attendance and poor retention rates at a HIV treatment programme in rural Tanzania.

Abstract Irregular or delayed attendance at HIV treatment clinics among HIV-positive individuals can have negative implications for clinical outcomes and may ultimately undermine the effectiveness of national treatment programmes. This study explores factors influencing attendance at HIV clinic appointments among patients in a rural ward in north-west Tanzania. Forty-two in-depth interviews (IDI) and four focus group discussions were conducted with HIV-infected persons who had been referred to a nearby antiretroviral therapy (ART) clinic, and IDI were undertaken with 11 healthcare workers involved in diagnosis, referral and care of HIV-positive patients. The Health Belief Model was applied to explore the role of health-related beliefs and the perceived barriers and benefits associated with regular clinic attendance. Perceived susceptibility to HIV-related illnesses emerged as an important factor influencing clinic attendance, and was often manifest through expressions of acceptance or denial of HIV status and knowledge of HIV disease progression. Denial of HIV status was often associated with using alternative healers, and could occur prior to, during, or after starting ART. Perceptions of illness severity also influenced HIV clinic attendance, and often evolved in relation to changes in physical symptoms. Barriers to clinic attendance frequently included health systems factors, while physical and social benefits encouraged regular clinic attendance. Self-confidence in being able to sustain clinic attendance was often determined by patients’ expectations or experiences of family support. These findings suggest that multi-faceted interventions are required to promote regular HIV clinic attendance, including on-going education, counselling and support in both clinic and community settings. These interventions also need to recognise the evolving needs of patients that accompany changes in physical health, and should address local beliefs around HIV aetiology. Decentralisation of HIV services to rural communities should be considered as a priority to redress the balance between perceived barriers to, and benefits of accessing HIV treatment programmes.

The four-parameter logit life table system.

Summary Brasss model life table system, which is a two parameter system based on the logit transformation of survivorship values, has been widely and successfully used to describe age patterns of mortality in many populations. As more reliable information has become available for populations with mortality patterns which differ in important ways from the assumed standard pattern of mortality, a more flexible model system is needed. This paper shows how Brasss system can be expanded into a four-parameter model, and evaluates the performance of the new system by examining how well it can fit observed life table data.