HIV Positive Tuberculosis Patients Need to Start Antiretroviral Treatment Early

Deaths among people infected with both tuberculosis (TB) and HIV could be halved if patients start antiretroviral therapy before they finish 6 months of TB treatment, according to results of a new study by researchers at the University of KwaZulu-Natal in South Africa.

TB is the most common opportunistic disease affecting people with HIV in South Africa. Some 353,000 people in the country were diagnosed with TB last year, about 70% of whom were also infected with HIV; in addition, extensively drug-resistant TB is a growing problem. Treatment for both HIV and TB requires multiple drugs, resulting in the potential for drug-drug interactions and increased side effects, including liver toxicity.

Given the public health concern about resistance to TB drugs, patients are typically started on multiple TB drugs simultaneously. Standard practice has been to start anti-HIV therapy a few months later, or even after the full 6 to 8 month course of TB treatment is completed.

According to World Health Organization (WHO) guidelines, only HIV patients with a CD4 count below 200 cells/mm3 -- who are at high risk for AIDS-related opportunistic illnesses -- should start antiretroviral therapy during TB treatment, leaving it unclear how best to manage coinfected individuals with higher CD4 counts.

To answer this question, researchers with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) studied the optimal time to start antiretroviral treatment in patients infected with both HIV and TB.

The open-label trial -- dubbed "Starting Antiretrovirals at Three Points in Tuberculosis," or SAPIT -- compared mortality rates among HIV-TB coinfected patients receiving integrated (concurrent) antiretroviral and TB treatment or sequential treatment for TB then for HIV. A total of 645 coinfected participants with a CD4 count below 500 cells/mm3 were randomly allocated into 3 groups:

• Those who started antiretroviral therapy after 2 months of TB treatment;

• Those who started antiretroviral drugs 2 to 6 months after starting TB treatment;

• Those who started antiretroviral therapy after completing a full 6 to 8 months of TB treatment.

Interim results from the study showed that the risk of death was 55% lower among patients who started antiretroviral therapy within 6 months, while they were still undergoing TB treatment. During follow-up, 26 of 214 people in the sequential treatment group died, compared with 24 of 431 participants in the 2 integrated treatment arms.

Based on these findings, the sequential treatment arm was halted and those patients were started on antiretroviral therapy; the study is still ongoing to compare the 2-month and 2 to 6-month integrated treatment arms.

As many as 10,000 deaths a year could be prevented in South Africa if HIV-TB coinfected patients were to start anti-HIV treatment sooner, said Salim Abdool Karim, CAPRISA director and principal investigator of the study. He estimated that last year there were 150,000 coinfected patients with CD4 counts between 200 and 500 cells/mm3 who potentially could have benefited from earlier antiretroviral therapy.

The findings underline the need to integrate HIV and TB services in clinics and hospitals, he added. "The study shows that integrating TB and HIV treatment and care saves lives."

9/26/08

Sources

Centre for the AIDS Programme of Research in South Africa. Important New Research Findings on Treatment of TB-HIV Co-Infection. Press release. September 19, 2008.

T Kahn. TB patients Need AIDS Drugs Early. Business Day. September 18, 2008.