Large-scale impact of ART on mortality in Brazil, South Africa: big successes but mind the gaps

Studies from two developing countries that have prioritised the scale-up of ART further demonstrated the potential for treatment to have a dramatic impact on HIV-related mortality in resource-limited settings today at the Eighteenth International AIDS Conference in Vienna.

However, the studies also showed that some groups are benefiting less from ART due to late presentation for care, poverty and marginalisation, and that TB remains a major challenge to ART programmes.

In Brazil, which in 1996 became the first developing country to provide free universal access to ART, researchers analysed patient data from four national information systems and concluded that treatment access accounted for the declines they found in HIV-related mortality. A second Brazilian study documented increasingly higher survival rates among HIV-positive children diagnosed between 1983 and 2002.

Additionally, a South African study found a dramatic reduction in deaths in a cohort of more than 40,000 platinum miners after the introduction of ART in mid-2003.

The first Brazilian study used regression analysis to assess the impact of access to ART on four exposure categories: injecting drug users (IDUs), men who have sex with men (MSM), heterosexual males and heterosexual females. All individuals whose records were included in the study were diagnosed with HIV between 1998 and 2008.

The full cohort included 382,012 people, 17% of whom acquired HIV through injecting drug use. During ten years of follow-up, 121,346 people died. After ART became available in 1996, declines were seen in HIV-related mortality rates for both men and women, and for all exposure categories.

Injecting drug users continue to benefit less from universal access to antiretroviral therapy in Brazil. Monica Malta, Oswaldo Cruz Foundation, Brazil

Some notable differences were found among the groups studied. Heterosexual women were diagnosed earlier and presented the lowest case-fatality rate, followed by MSM, heterosexual men and IDUs.

After adjusting for sex, ethnicity, age at AIDS diagnosis and baseline CD4 cell count, researchers observed that IDUs had the highest risk of death after ten years of follow-up (aHR 1.77 compared to MSM) (p<0.001). Non-white individuals also had a higher risk of death (aHR 2.65).

Injecting drug users continue to benefit less from universal access to antiretroviral therapy in Brazil, said Monica Malta of Brazil’s Oswaldo Cruz Foundation, presenting the results.

The other Brazilian study drew on data from two retrospective cohort studies of children under age 13 diagnosed with AIDS  in 1993-1998 (n=914) and 1999-2002 (n=920). Both samples were randomly drawn from all reported cases nationally.

The pooled data indicated that the probability of survival to 60 months increased by 4.5-fold from 1983 to 2002. For the 1983-1987 period, 60-month survival was 19.7% (11.2 to 30.0%; n=16), and for the next four-year period, it was 27.3% (22.9 to 31.9%; n=265).

In 1993-1994, 60-month survival rose to 39.7% (33.4 to 45.9%; n=196). It reached 59.5% in 1995-1996 (52.8 to 65.6%; n=221); 68.2% in 1997-1998 (61.6 to 73.9%; n=216); 86.5% in 1999-2000 (83.0 to 89.3%; n=470); and 90.2% in 2001-2002 (87.0 to 92.7%; n=450).

Kaplan-Meier analysis showed that the majority of mortality in children diagnosed after 1999 occurred in the first two years after diagnosis, indicating the higher risk of HIV-related mortality during early life and the importance of early diagnosis and treatment of children with HIV. Brazil recommended treatment for all children with HIV under one year of age in 2009.

Presenter Luiza Matida said that, while the data showed that it is possible to provide high-quality ART services for children in a country as large and diverse as Brazil, the country faced two major challenges in the years ahead: sustaining high-quality care, and meeting the needs of adolescents as the population of children with HIV grows up.

The South African study analysed retrospective data from a cohort of 41,290 male platinum miners in the North-West province, using data from employees at one mine which provided free health care, including voluntary counseling testing, TB treatment and from mid-2003, free antiretroviral drugs.

HIV prevalence among the employee cohort was very high, estimated at approximately 27% in 2002. The study tracked mortality among all semi-skilled and unskilled employees and for up to one year after employees left the workforce due to medical retirement.

The study accumulated 280,918 person-years of follow, and observed 3277 deaths, an average mortality rate of 11.9 per 1000 person-years of follow-up. Forty-eight per cent of the deaths were due to AIDS, and 24% due to violence or personal injury.

Between 1992 and 2003, mortality increased greatly to a peak of 20 per 1000 person-years, driven almost entirely by AIDS-related deaths, then – following the introduction of ART in 2003 – there was initially a sharp drop in mortality to 12 per 1000 person-years by 2006. In 2007 and 2008, however, mortality was once again on the rise, to 15 per 1000 person-years.

Between 2003 and 2008, 45% of deaths were attributed to HIV-related causes. Only 29% of individuals who died were known to have been taking ART. Nearly half of the men who died had never registered with the mine’s medical service. Qualitative research suggested a high degree of resistance among miners to medical care. There was common denial of HIV status, or the risk of HIV infection, and many men told researchers they did not believe that antiretroviral drugs worked. The fear of taking time off work and losing wages was also a reason for not using medical services, they said.

But another potential contributing factor to the rising death rate may have been the high death rate from TB. Nearly half the deaths that occurred in the period 2003 to 2008 were TB-related, and the mine company’s main response to the findings has been to focus on integrating its HIV and TB care and prevention much more closely, said Megan Lim of University College, London, presenting the findings.

Lim M et al. The impact of HIV/AIDS and antiretroviral therapy on mortality in South African platinum miners, 1992-2008. 18th International AIDS Conference,  abstract TUAC0104, Vienna, 2010.

Malta M et al. Survival benefit of universal HAART access in Brazil: a ten-years nation-wide comparison. 18th International AIDS Conference, abstract TUAC0102, Vienna, 2010.

Matida LH et al. Positive impact on survival for children with AIDS in Brazil: combined analysis of two national studies, 1983-1998 and 1999-2002. 18th International AIDS Conference, abstract TUAC0103, Vienna, 2010.

Presentations by the speakers and their related abstracts are available on the official conference website.