Tuberculosis
(TB) is the most common opportunistic infection and the leading cause of death
in people with HIV worldwide. An extremely drug-resistant
form of the disease (XDR-TB) was described in South Africa last year, and has
now been reported throughout the world, including a recent case in an American
man who was quarantined after taking an international airline flight.
The
standard treatment for TB is a combination of antibiotics -- including drugs from
the rifamycin class -- taken for 6 months (4 drugs for the first 2 months, followed
by 2 drugs for the remaining 4 months). Past research has suggested that this
regimen is adequate for both HIV negative and HIV positive patients.
But
a new study reported in the June 1, 2007 American Journal of Respiratory and
Critical Care Medicine indicates that HIV positive TB patients are more likely
to experience relapse after 6 months of therapy and may benefit from longer treatment.
The
present study evaluated treatment outcomes for HIV-infected patients stratified
by duration of rifamycin-based TB therapy. The investigators retrospectively reviewed
data from all TB patients reported to the San Francisco Tuberculosis Control Program
between 1990 and 2001. Out of 700 total subjects, 264 (38%) were HIV positive,
315 (45%) were HIV negative, and 121 (17%) were not tested for HIV.
HIV
negative subjects and those with unknown HIV status with active TB were treated
for a mean duration of 8.4 months, while HIV positive patients were treated for
a mean 10.2 months. To avoid drug interactions, HIV
positive patients receiving concurrent HAART were treated with rifabutin instead
of rifampicin. Subjects were followed for up to 12 months after completion of
therapy.
Results
•
17%
of HIV positive patients and 37% of the HIV negative and unknown serostatus patients
received 6 months of rifamycin-based therapy.
•
Patients
with HIV were significantly more likely to receive longer courses of therapy.
•
The
relapse rate among HIV positive patients was 9.3 per 100 person-years (PY), compared
with 1.0 per 100 PY among HIV negative and unknown serostatus patients (P <
0.001).
•
HIV
positive subjects who received the standard 6-month course of rifamycin-based
therapy were significantly more likely to relapse than those treated for longer
durations (24 vs 7 per 100 PY; adjusted hazard ratio 4.33; P = 0.02).
•
HIV
positive individuals who received intermittent therapy were also more likely to
relapse than those treated on daily basis (adjusted hazard ratio 4.12; P = 0.04).
•
The
only factors independently associated with a higher risk of relapse were being
HIV positive and receiving intermittent therapy.
•
HIV
positive patients were significantly more likely to die while undergoing or within
12 months after TB treatment (relative risk 5.19; P < 0.001).
•
Concurrent
use of HAART was associated with a lower TB relapse rate, more rapid conversion
to negative TB sputum smears and cultures, and fewer side effects related to anti-TB
drugs.
•
None
of the patients on HAART were among those who experienced TB relapse.
•
HAART
was also associated with improved survival.
Conclusion
"HIV-infected
patients who received a 6-month rifamycin-based course of tuberculosis treatment
or who received intermittent therapy had a higher relapse rate than HIV-infected
subjects who received longer therapy or daily therapy, respectively," the
authors concluded. "Standard 6-month therapy may be insufficient to prevent
relapse in patients with HIV."
In order to avoid drug interactions
and immune reconstitution inflammatory syndrome, some guidelines
recommend that TB treatment should be completed before starting HAART in individuals
with high CD4 cell counts, or that HAART should delayed for 2 months in patients
with low CD4 counts. However, the researchers said their results "provide
compelling evidence to warrant the initiation of [HAART] during tuberculosis treatment
in selected patients."
In
an accompanying editorial, David Perlman and co-authors wrote that given the recent
emergence of XDR-TB, a reappraisal of treatment strategies for HIV positive TB
patients seems timely. Adequate treatment plays an important role in preventing
the emergence of drug-resistant TB bacteria.
Division of Pulmonary and
Critical Care Medicine, San Francisco General Hospital, University of California,
San Francisco, CA; Tuberculosis Control Section, Department of Public Health,
San Francisco, CA; Stanford University, Stanford, CA; Division of Mycobacterial
and Respiratory Infections, National Jewish Medical and Research Center, Denver,
CO.
06/15/07
References
P
Nahid, LC Gonzalez, I Rudoy, and others. Treatment Outcomes of Patients with HIV
and Tuberculosis. American Journal of Respiratory and Critical Care Medicine
175(11): 1199-1206. June 1, 2007.
DC Perlman, CC Leung, and WW Yew. Treatment
of Tuberculosis in HIV-infected Patients: We Need to Know More. American Journal
of Respiratory and Critical Care Medicine 175(11): 1102-1103. June 1, 2007.
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"HIV-infected
patients who received a 6-month rifamycin-based course of tuberculosis treatment
or who received intermittent therapy had a higher relapse rate than HIV-infected
subjects who received longer therapy or daily therapy, respectively," the
authors concluded. "Standard 6-month therapy may be insufficient to prevent
relapse in patients with HIV."
