Tuberculosis is the infection most likely to cause death in HIV patients, according to a series of articles in the October 20, 2011 issue of the New England Journal of Medicine. Treating the two infections simultaneously presents a challenge. Dr. M. Estee Torok and Dr. Jeremy J. Farrar explained that early treatment with antiretroviral drugs poses both risks and benefits.
Patients with HIV may not seek medical care until they develop symptoms of tuberculosis. Torok and Farrar reported, “current guidelines recommend that ART [antiretroviral therapy] be initiated 2 to 8 weeks after the initiation of tuberculosis therapy in all patients who present with HIV-associated tuberculosis.”
The optimum timing may depend on how advanced the HIV infection is, as measured by the CD4+ T-cell count.
When antiretroviral therapy is started early, within two weeks of tuberculosis therapy, the risks include:
1. Immune reconstitution inflammatory syndrome (IRIS). This is a worsening of tuberculosis symptoms after antiretroviral therapy is started.
2. Possible poor adherence to therapy because of the high pill burden. Four antibiotic drugs for tuberculosis, three antiretroviral drugs for HIV, and antimicrobial prophylactic drugs to prevent further opportunistic infection are standard. This regimen may be overwhelming for some patients.
3. Drug interactions and toxicities. Each drug has its own adverse effects, and the combination may be poorly tolerated.
On the other hand, early antiretroviral treatment can improve the immune response to tuberculosis and other opportunistic infections. Several studies have been performed to evaluate the trade-offs.
The CAMELIA (CAMbodian Early versus Late Introduction of Antiretrovirals) study showed the highest benefits for early antiretroviral treatment. Dr. Francois-Xavier Blanc and colleagues studied 661 patients with newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower.
The early treatment group started antiretroviral treatment two weeks after tuberculosis treatment, and the later treatment group started antiretroviral treatment eight weeks after tuberculosis treatment.
The early treatment group had significantly better survival over the follow-up period, with a median of 25 months. IRIS was significantly increased in the early treatment group, with six deaths, but overall this group had 59 deaths among 332 patients (18 percent), compared to 90 deaths among 329 patients (27 percent) in the later treatment group.
Torok and Farrar reported that the CAMELIA results may not apply to patients with more severe forms of tuberculosis, such as tuberculous meningitis, or to those with higher CD4+ T-cell counts.
References:
1. Torok ME et al, “When to start antiretroviral therapy in HIV-associated tuberculosis”, New England Journal of Medicine 2011 October 20; 365(16): 1538.
http://www.nejm.org/doi/full/10.1056/NEJMe1109546?query=TOC
2. Blanc FX et al, “Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis”, New England Journal of Medicine 2011 October 20; 365(16): 1471.
http://www.nejm.org/doi/full/10.1056/NEJMoa1013911
Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.
Reviewed December 8, 2011
by Michele Blacksberg RN
Edited by Jody Smith