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Studies Further Identify Risks for TB While on HAART

By Alan McCord

September 2008

Globally, diagnosing and treating tuberculosis (TB) in people living with HIV is becoming more difficult, as multi-drug resistant and extensively resistant strains become more common. This difficulty is often worsened by the lack of testing resources, access to drugs, and health care infrastructures. In spite of these complex issues, it's becoming more imperative to properly screen and treat individuals at risk for TB disease. Several studies on TB/HIV co-infection reported results at the International AIDS Conference.

Risk Factors for TB Within First 3 Months on HAART

This retrospective study examined data from 12 cohorts of 9,937 HIV-positive people in North America. Researchers compared the risk of TB within and after the first 3 months on HAART. No one who had TB before or in the same month of starting HIV therapy (HAART) was included. However, those with earlier AIDS-defining conditions, except TB, were included.

Four cases of TB were found within the first 3 months on HAART, while 38 cases of TB were found afterwards. The risk factors found for the 4 were low CD4 counts (below 100 cells) and high viral loads (above 250,000). No differences were seen by age, sex, race, place of disease (inside vs. outside lungs), TB status (positive vs. negative), and type of HAART that was used.

These results show the need for health providers to thoroughly screen (and treat as needed) people who have low CD4 counts and high viral loads when starting HIV therapy. These are not radically new suggestions for assertive screening and treatment of opportunistic infections (OIs), as many OIs occur at these levels. What's clearer is that the risk for TB disease in these individuals is more pronounced before and within the first three months on HAART.

When to Start HAART After a TB Diagnosis

The best time to start HAART after a diagnosis of TB remains somewhat unclear. The Brazilian THRio study examined a large group of individuals for length of survival after a TB diagnosis. It compared the impact of HAART over time as well as its timing on survival.

This retrospective study examined the records of more than 15,000 people with HIV. The study identified three groups for comparison: starting vs. not starting HAART after a TB diagnosis; starting HAART during vs. after TB treatment; and starting HAART within 60 days, 61-180 days, and over 180 days of a TB diagnosis. Men comprised 66% and women 34% of the study.

A total of 660 were diagnosed with TB and 461 of them had started HAART. Those who started HAART after a TB diagnosis had a significantly lower risk of death than those who didn't start HAART. Those who completed their full treatment for TB were also less likely to die and had better outcomes than even those on HAART alone. However, the results showed that timing the start of HAART had no significant effect on survival, nor did the three ranges of time studied.

These results are not surprising, as it has often been shown that taking HAART as prescribed improves health outcomes and helps resolve opportunistic infections (OIs) such as TB. This would also include completing any therapy for an OI such as TB. Interestingly, however, these study results contrast with another study's results (directly below) that show starting HAART sooner after a TB diagnosis lowers the rate of death.

Starting HAART and Its Impact on Survival

A small retrospective study from Iran examined 69 people with both HIV and TB over 5 years. Two groups were compared. The first had CD4 counts below 200 and started HAART after 8 weeks on TB therapy. The other group started HAART either 2 weeks after starting TB therapy (if CD4 counts were below 100) or 8 weeks after starting TB therapy (if CD4 counts were 101-200 cells). The study looked at the response to TB therapy, liver function and the development of IRIS (immune reconstitution inflammatory syndrome) or new OI.

Results showed that the two groups were comparable in terms of drug reactions and the development of IRIS or a new OI. However, the second group -- who in general started HAART earlier after taking TB therapy -- showed fewer deaths. These data conflict with results found in the study directly above, though this may or may not be significant. Because this was a smaller study, the fewer deaths may not represent a conclusion that could be made to a larger population.

Final Thoughts

Worldwide, 2 billion people are infected with TB, while 9.2 million new cases of TB disease occur and 2 million die each year. Resource-poor areas of the world find it difficult and often impossible to adequately detect and treat those living with both HIV and TB. The newer, harder-to-treat strains of TB further complicate medical decisions.

From the studies mentioned above and others, two lab markers are associated with higher risk for TB disease. These are high viral load of 250,000-350,000 or more and low CD4 cell counts below 100. In these individuals with advanced HIV disease, it's wise to aggressively screen for TB infection and disease just before and within the first 3 months of starting HAART.

It's clear from many studies that being on HAART helps resolve TB infection and disease, provided that the treatments for both are taken as prescribed. However, the best time to start both (such as 2 weeks or 8 weeks apart, for example) is still not clear. These results do point to more aggressive screening of those at risk for TB right before and after starting HAART. These tools include not only PPD skin tests, anergy tests and chest x-rays, but also and perhaps more importantly sputum samples and cultures that show actual bacteria.

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