Nuala McGrath

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.

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis:

In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.

Profile: The Karonga health and demographic surveillance system

The Karonga Health and Demographic Surveillance System (Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002–2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behaviour, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades.

Dispensing with marriage: Marital and partnership trends in rural KwaZulu-Natal, South Africa 2000-2006

This paper describes marriage and partnership patterns and trends in rural KwaZulu-Natal, South Africa from 2000-2006. The study is based on longitudinal, population-based data collected by the Africa Centre demographic surveillance system. We consider whether the high rates of non-marriage among Africans in South Africa reported in the 1980s were reversed following the political transformation underway by the 1990s. Our findings show that marriage has continued to decline with a small increase in cohabitation among unmarried couples, particularly in more urbanised areas. Comparing surveillance and census data, we highlight problems with the use of the ‘living together’ marital status category in a highly mobile population.

Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.

A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection

BACKGROUND Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. METHODS In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. RESULTS The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). CONCLUSIONS In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.

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.

Population Differences in Immune Responses to Bacille Calmette-Guérin Vaccination in Infancy

Bacille Calmette-Guérin (BCG) vaccination induces a marked increase in the interferon (IFN)-gamma response to Mycobacterium tuberculosis purified protein derivative (Mtb PPD) in UK adolescents, but not in Malawian adolescents. We hypothesized that Mtb PPD-induced IFN-gamma after BCG vaccination would be similar in infants from these 2 countries. Infants were vaccinated with BCG during the first 3-13 weeks of life. Three months after BCG vaccination, 51 (100%) of 51 UK infants had an IFN-gamma response to Mtb PPD, compared to 41 (53%) of 78 of Malawian infants, in whom responses varied according to their season of birth. We conclude that population differences in immune responses after BCG vaccination are observed among infants, as well as among young adults.

Age at first sex in rural South Africa

Objectives: To identify factors associated with sexual debut and early age at first sex (AFS) among young men and women (12–25 years) in a population with a high prevalence and incidence of HIV in rural South Africa. Methods: Longitudinal data from four rounds (2003–7) of a prospective population-based HIV and sexual behaviour survey in rural KwaZulu-Natal were used to investigate the distribution and predictors of earlier first sex. Survival analyses were used, and each analysis considered men and women separately. Results: Among the 4724 women and 4029 men who were virgins at the beginning of the period, the median AFS was 18.5 and 19.2 years, respectively. In multivariable models, factors associated with earlier AFS across gender were periurban residence (vs rural), ever use of alcohol and knowing at least one person who had HIV, while school attendance had a significant protective effect. Other factors were important for one gender only. Maternal death was significantly associated with earlier AFS for women, in the same way that paternal death was for young men, while mother’s membership of the same household significantly delayed AFS of young men. The analysis of early first sex confirmed the same factors to be important as in the overall analyses for men and women. Conclusion: Given the association of individual, household and community level factors with sexual debut, a multisectorial approach to prevention and targeting in youth programmes is recommended.

Gender, Migration and HIV in Rural KwaZulu-Natal, South Africa

Objectives Research on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which womens migration contributes to their high infection risk. Design Data on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15–49 and men aged 15–54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003–04. Methods Logistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations. Results Relative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49–1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07–3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23–1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02–1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12–1.32]) and 46% for female migrants (aOR = 1.46 [1.25–1.69]). Conclusions Higher risk sexual behavior in the context of migration increased womens likelihood of HIV infection.