HIV-positive people with active tuberculosis are more likely to experience a relapse of the disease after receiving the same treatment typically used to manage HIV-negative TB patients, according to results from a large retrospective study published in the June 1 issue of the American Journal of Respiratory and Critical Care Medicine. The study suggests that six months of treatment may be insufficient to prevent a recurrence of the respiratory disease in people living with HIV.
Lead researcher Dr. Payam Nahid and his team set out to evaluate how well HIV-positive patients with active (culture-positive) TB responded to standard rifamycin-based treatment over time. The reason, according to Nahid, was that previous studies evaluating the optimal duration of TB therapy in HIV-positive patients, compared to those not infected with the virus, varied considerably and did not allow for any hard conclusions.
"Most of the studies have been highly controlled studies," said Nahid, who's also a clinician and assistant professor at the University of California, San Francisco. "The benefit of our study is that it looked at what actually happened in a real-life setting."
Nahid's "real-life setting" involved a case review of 700 tuberculosis cases reported to the San Francisco Tuberculosis Control Program from 1990 to 2001. Patients were followed for up to 12 months after they completed treatment. Of the patients included in the analysis, 264 were HIV infected, 315 were HIV negative, and the remaining 121 didn't have a confirmed HIV test result on file.
They found that the TB relapse rate among the HIV-infected patients was 6.6%, compared to 0.8% among the uninfected/status-unknown patients. This difference was statistically significant, meaning that it wasn't due to chance. Dr. Nahid's group also notes that this finding contradicts data from other studies that failed to spot a difference in relapse rates between HIV-positive and HIV-negative patients undergoing TB treatment.
HIV-positive patients who received the six-month TB drug regimen – using either the standard daily dosing or the alternative once-, twice-, or three-times weekly schedule – were four times as likely to experience a relapse, compared to those treated longer.
Dr. Nahid's team also found that tests of phlegm samples (cultures) for Mycobacterium tuberculosis – the bacteria responsible for the disease – became negative earlier in the course of TB treatment among HIV-positive patients who were taking antiretrovirals, compared to those who weren't.
"In our study, none of the patients receiving highly active antiretroviral therapy relapsed," noted Nahid. "But the sample size was not large enough to make a definitive statement." As the analysis included data from studies conducted before the widespread use of combination antiretroviral therapy, only 32 HIV-positive patients were on such treatment.
The fact that HIV and TB frequently go hand-in-hand is not lost on public health experts. Reuters reported on June 7 that Kevin de Cock, MD, head of the World Health Organization's (WHO) Department of HIV/AIDS, recently said at the 3rd South African ADS Conference that the linkage of TB testing and treatment with HIV treatment programs is imperative.
TB infection remains the most common opportunistic infection among people living with HIV globally. The WHO estimates that worldwide, there are more than 8 million new TB infections and nearly 2 million TB related deaths each year. They also estimate 10 million people all over the globe to be coinfected with tuberculosis and HIV.
When TB is not treated adequately, drug resistance can occur and, ultimately, be transmitted to others. In Dr. Nahid's study, HIV-infected patients were significantly more likely to develop drug resistance (4.2% vs. 0.5%) to rifampin.
Though diagnosed with latent TB infection – culture-negative infection that is not likely to spread to others – the recent case of Atlanta-based lawyer Andrew Speaker underscores the growing problem of multiple- and extensively drug-resistant TB. The fact that such highly drug-resistant forms of a curable disease are now being documented is a major source of concern to Dr. Nahid.
"We could have done something about this decades ago, but countries didn't do anything about it," said Nahid. "Our TB infrastructure has largely been ignored globally. It is believed not to be a problem."
An editorial that accompanies the San Francisco study, written by David C. Perlman, MD, of Beth Israel Medical Center in New York and colleagues of his in China, concurs with Dr. Nahid's assertion that there are many factors driving HIV and TB coinfections. They note that "both TB and HIV are associated with multiple adverse social factors, and social inequities are commonly associated with suboptimal health care infrastructures in many resource limited areas."
Nahid said that a huge problem is the lack of research for tools that shorten the diagnosis time, and for new treatments, noting that the "current drugs are 35 years old – compare that to HIV drugs and the difference is astounding."
Is TB something that U.S. residents with HIV need to worry about? In 2006, the U.S. Centers for Disease Control and Prevention (CDC) reported 13,767 cases of active TB. The overall rate of new TB infections continues to decline, including among people with HIV. From 2005 to 2006, the percentage of TB cases with HIV infection decreased 4.4% (from 13.0% to 12.4%).
"The biological reasons for HIV-positive people contracting TB are the same regardless of geographic location," said Nahid. "The U.S. is considered a low prevalence country. The incidence in the U.S. is hypothetically lower, but that risk of progressing to active TB infection is the same once you come into contact."
Sources:
Nahid P, Gonzalez LC, Rudoy I, et al. Treatment outcomes of patients with HIV and tuberculosis. Amer J Respir Crit Care Med 175:1199-1206, 2007.
Perlman DC, Leung CC, Yew WW. Treatment of tuberculosis in HIV-infected Patients. We need to know more. Amer J Respir Crit Care Med 175:1102-3, 2007.
