TB prophylaxis benefits HIV patients
Treatment with the anti-tuberculosis agent isoniazid appeared to protect HIV-infected individuals who live in areas where tuberculosis is highly prevalent -- at least for the short-term, two research teams found.
In one study, HIV-infected patients who took isoniazid for a year had a 37% reduced risk of coming down with tuberculosis, said Molebogeng Rangaka, MBChB, of the University of Cape Town in South Africa and the London School of Hygiene and Tropical Medicine reported in a late-breaker presentation studies at the International AIDS Conference.
In the second study, a retrospective analysis determined that a 6-month course of isoniazid therapy reduced the risk of tuberculosis by 48% over 18 months, according to Tadresse Teferi Mekonen, MD, HIV clinical mentor at the International Training & Education Center for Health in Windhoek, Namibia.
Rangaka and colleagues in South Africa recruited more than 1,300 patients for their prospective trial, assigning 667 of them to placebo. The rate of tuberculosis in that group was 3.6 cases per 100 person years. That compared with 2.3 cases per 100 person years among the 662 patients who were assigned to receive isoniazid – a reduction of 37% (P=0.03).
There was no statistically significant difference in survival – 21 deaths occurred in the placebo group, 16 in the isoniazid patients (P=0.32)
Elevated liver enzymes were observed in 1.3% of placebo patients and 2.9% of isoniazid patients (P=0.05).
The researchers undertook the pragmatic, randomized, placebo-controlled clinical trial in e-Khayelitsha, Cape Town, a community of 600,000 people with a high prevalence of both diseases. The tuberculosis rate is 1,600/100,000 people. An antenatal HIV clinic shows an HIV prevalence of 33.3%, Rangaka said.
"Twelve months of isoniazid prevention treatment reduced the incidence of all tuberculosis diagnoses among patients concurrently on antiretroviral therapy," Rangaka said.
Participants were followed for 3 years. The patients in both study groups had comparative CD4-positive cell counts. Both groups also received highly active antiretroviral therapy.
In the isoniazid patients, no tuberculosis events were recorded among 482 patients; 69 developed a tuberculosis event; 111 transferred out of the program or were lost to follow-up, There were 84 events among the placebo patients; no events occurred in 469 patients; 114 transferred out of the program or were lost to follow up.
The median age of the patients in the study was 34 years; about three-quarters of the patients were women; more than 40% of the patients had a previous tuberculosis diagnosis. The median time on antiretroviral medication was about a year.
In the second study, Mekonen and colleagues reviewed health records of 1,100 patients treated at Okongo Hospital in northern Namibia. "Among our adult patients receiving isoniazid preventive therapy, about 95% were free of tuberculosis infection after 18 months, compared with 65% of patients who did not undergo isoniazid treatment," he told MedPage Today at his poster presentation.
He said that 6 months of isoniazid preventive therapy reduced the cumulative cases of tuberculosis by 48% (P<.0001). But, Mekonen also observed, after 18 months, the protective effect of 6-months of isoniazid waned.
After 2 ½ years the difference in protection was no longer statistically significant, and by 3 ½ years there was no apparent benefit to having receiving the preventive treatment.
The median time between stopping of isoniazid therapy and the observation of tuberculosis infection was 30 months, he said.
"This may indicate the need for re-prophylaxis in patients residing in tuberculosis endemic setting," Mekonen said.
He said northern Namibia is the population center of the country and has high prevalence of both HIV and tuberculosis.
The overall risk of death was about 10%, with 99 deaths occurring in the group not receiving preventive therapy, and only 11 deaths occurring in those on preventive treatment (P<.0001).
The study included 1,115 individuals who were followed for 3770.8 person years. About 82% of the individuals were on antiretroviral therapy; 67.3% of the patients were women.
None of the patients in this study had been previously diagnosed with tuberculosis and none had previously received prophylaxis. They were treated at the hospital from March 2005 to February 2009 and were followed until November 30, 2011.
The researchers analyzed their data in several different models, but in every case, prophylactic treatment was statistically significantly beneficial – up to 18 months. The univariate analysis favored prophylaxis (P=.0004).
Adjusting for sex favored prophylaxis (P=.0001); if the sample was corrected for sex and weight (P.0001), or if the analysis was based sex, weight, and WHO clinical stage, (P<.0001) prophylaxis proved a benefit.
Rangaka and Mekonen had no disclosures.
Primary source: XIX International AIDS Conference 2012
Source reference:
Teferi T, et al "WEPE066 - Effect of primary isoniazid preventive therapy on tuberculosis incidence rate among HIV-positive adults enrolled in HIV care in northern Namibia: a retrospective cohort study," IAC 2102; Abstract.
Additional source: XIX International AIDS Conference 2012
Source reference:
Rangaka M, et al "THLBB03: Randomized controlled trial of isoniazid preventive therapy in HIV-infected persons on antiretroviral therapy," IAC 2012; Abstract.
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