By Liz Highleyman

Tuberculosis acts as an opportunistic illness in people with HIV, and the widespread AIDS epidemic in South Africa is associated with a concurrent epidemic of TB, as well as outbreaks of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) disease.

HIV-related immune suppression increases the risk of developing active TB disease, and conversely, effective combination antiretroviral therapy (ART) has been shown to improve outcomes in HIV-TB coinfected individuals.

Township outside Cape Town (Photo: Liz Highleyman)

Clinic in Gugulethu (Photo: Liz Highleyman)

Keren Middelkoop from the Desmond Tutu HIV Centre in Cape Town and colleagues undertook a study to see whether ART would have a beneficial effect on TB rates at the population level. The investigators assessed HIV and TB rates over time in a township outside Cape Town with a population estimated at 15,000 people.

The community has a well-functioning TB prevention and treatment program based on short-course directly observed therapy (DOTS), and was included in an effort to roll out and scale up HIV treatment starting in the mid-2000s. All TB patients in the community are treated at a single clinic. National program guidelines for diagnosis and management of TB did not change significantly over the study period.

By 2008, nearly one-quarter of the HIV positive population was receiving antiretroviral drugs double the proportion on treatment in 2005 representing about 90% of patients who need ART according to local guidelines (based on a threshold of 200 cells/mm3 or symptomatic disease, including active TB).

The researchers reported that annual TB reporting rates increased significantly between 1998 and 2004, coinciding with an increased rate of HIV infections over the same period. TB notifications peaked in 2005, the year the widespread ART roll-out began possibly attributable to increased TB screening of individuals seeking ART and thereafter started to decline.

In 2005 and 2008, the researchers conducted cross-sectional surveys of random samples of adults in the community (762 people in 2005 and 1251 in 2008). The mean age was about 30 and men and women were equally represented. Participants received sputum smears to test for TB as well as oral HIV testing.

Based on the 2005 survey, the investigators previously reported a high prevalence of undiagnosed TB prior to widespread ART availability, with HIV positive individuals being more likely than HIV negative people to have undiagnosed TB. In a late-breaker oral presentation at this week's conference they reported follow-up date from the 2008 survey.

Results

	In the cross-sectional surveys, TB prevalence fell from 3% of sampled participants in 2005 to 1.8% in 2008.
	During this same period, HIV prevalence among surveyed individuals rose slightly, from 23% to 25%.
	Among HIV positive people, TB prevalence fell from 9.2% to 3.6% after the ART roll-out (P = 0.02).
	Among HIV negative individuals, however, the rate remained stable at around 1%.
	Similarly, previously undiagnosed TB cases among HIV positive people decreased from 5.2% to 1.3% (P = 0.01).
	Here too, the rate of undiagnosed among HIV negative participants stayed the same, at around 0.5%.
	TB notification rates for the population declined markedly from 2005 to 2008, but again the decrease was mostly attributable to HIV positive individuals.
	The overall TB reporting rate fell from about 2500 to about 2000 cases per 100,000 person-years (PY).
	Among HIV positive participants, the rate decreased from about 7000 to about 5300 per 100,000 PY.
	Among HIV negative people, the rate fell from about 1000 to about 500 per 100,000 PY.

"Wide-scale availability of ART appears to be associated with a decrease in prevalence of microbiologically confirmed TB in this community, predominantly in the HIV-infected population," the investigators concluded.

The researchers noted that there were no changes in TB program practices, death rates, or numbers of people leaving the community that could explain the decrease in TB seen in this study. TB-related mortality, in fact, decreased, especially among HIV positive people.

They added that the decline in TB could be attributable to a lower TB transmission rate (due to fewer infected individuals in the population), less reactivation of latent disease due to improved immune function, or some combination of these factors.

University of Cape Town; Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa; University of Cape Town, School of Public Health & Family Medicine and Department of Clinical Laboratory Sciences, Cape Town, South Africa; Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, National Health Laboratory Service, Cape Town, South Africa; University of Medicine and Dentistry of New Jersey, Public Health Research Institute, New Jersey; University of the Witwatersrand, Perinatal HIV Research Unit, Johannesburg, South Africa.

7/24/09

References

K Middelkoop, R Wood, L Myer, and others. Widespread ART is associated with decline in TB prevalence. abstract WeLBB105, 2009. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. July 19-22, 2009. Cape Town, South Africa (IAS 2009). Abstract WeLBB105.

K Middelkoop, R Wood, L Myer, and others. Can antiretroviral therapy contain a previously escalating TB epidemic in a high HIV prevalence community? 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. July 19-22, 2009. Cape Town, South Africa (IAS 2009). Abstract CDB041.

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