Starting ART reduces TB risk for HIV-positive patients in South Africa

Starting antiretroviral therapy (ART) significantly reduces the risk of tuberculosis (TB) for patients in South Africa, investigators report in the online edition of AIDS. Overall, ART initiation was associated with a 45% reduction in TB risk, which was lower than the effectiveness observed in other research. The authors believe this difference is because of their rigorous methodology, which unlike earlier studies, took into account patients’ pre-treatment CD4 counts.

“The study shows that ART initiation was associated with a substantially reduced risk of TB in HIV-infected patients with CD4+ cell counts of 350 cells/mm or less,” write the investigators. “The results differ from previous studies in high TB burden countries including South Africa, in which effectiveness estimates were greater and in which effectiveness was not modified by CD4+ count.”

TB is the commonest AIDS-defining illness in Africa. However, there is some evidence that ART rollout is reducing TB incidence among HIV-infected patients in this region. South Africa has the worst HIV epidemic in sub-Saharan Africa with an estimated 6.3 million infected patients. A national ART programme was introduced in 2004, and by 2010 approximately 2.4 million patients had started HIV therapy. Data from government health services suggest that increasing access to ART has been accompanied by a fall in TB incidence. Moreover, a meta-analysis of eleven studies in low- and middle-income countries estimated that ART reduced TB risk or incidence by 65%.

Glossary

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

meta-analysis

When the statistical data from all studies which relate to a particular research question and conform to a pre-determined selection criteria are pooled and analysed together.

low income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. While the majority of the approximately 30 countries that are ranked as low income are in sub-Saharan Africa, many African countries including Kenya, Nigeria, South Africa and Zambia are in the middle-income brackets. 

However, this study had an important limitation in that it did not take into account patients’ pre-treatment CD4 counts.

To get a better understanding of the true impact of ART initiation of TB risk, an international team of investigators designed an observational cohort study involving approximately 74,000 individuals who received HIV care in Free State, South Africa, between 2004 and 2010. TB risk and incidence was compared between patients who started ART and those who did not. Results were modified to take into account factors known to be associated with TB risk, especially CD4 count.

Patients were eligible to start ART if they had a CD4 count below 200 cells/mm3, had stage IV HIV disease (AIDS), or were pregnant with a CD4 count below 350 cells/mm3.

Approximately 44,000 patients (62%) started ART and 30,000 (38%) did not (or initiated HIV therapy after an episode of TB). Factors associated with starting ART were gender (female vs. male, p < 0.001), CD4 count below 200 cells/mm3 (p < 0.001), higher body weight (p < 0.001), previous TB (p < 0.001) and enrollment in the later years of the study (p < 0.001).

Patients were followed for up to 6.5 years (median, 1.3 years). Individuals who started ART contributed 78,202 person-years of follow-up and during this time, 3858 first TB cases were recorded (incidence, 4.9 per 100 person years). There were 5669 first TB cases during approximately 63,000 person-years of follow-up among patients who did not start ART (incidence, 9.0 per 100 person years). The investigators therefore calculated that, overall, starting ART reduced TB risk by 45% (crude incidence rate ratio, 0.55; 95% CI, 0.52-57).

Factors associated with reduced TB risk included ART (p < 0.001), higher CD4 count (p < 0.001), female sex (p < 0.001), older age (p < 0.001) and enrollment in later study years (p < 0.001).

Further analysis showed that ART reduced TB risk at all CD4 counts below 350 cells/mm3 (28-56% reduction in risk). The biggest risk reduction associated with ART initiation was observed in patients with CD4 counts below 100 cells/mm3.

Starting treatment after 2006 was also associated with a significant reduction in TB risk.

“The study shows that ART was effective in preventing TB, although less effective than in previous studies, and that effectiveness increased with time,” conclude the authors. “The study supports further expansion of ART as a foundation of TB control in South Africa and other high TB burden countries.”

References

Bachmann MO et al. Effect of antiretroviral treatment on the risk of tuberculosis during South Africa’s programme expansion: a cohort study. AIDS, online edition. DOI: 10.1097/QAD.0000000000000806, 2015.