Clinical Manual for Management of the HIV-Infected ... - myCME.com

Rifabutin may be substituted for rifampin to avoid
rifampin-ARV interactions. Rifabutin has less
marked effects on the pharmacokinetics of other
drugs compared to rifampin, although its own
blood concentrations can be affected by certain
ARVs. See Table 3 for dosing recommendations for
coadministration of rifabutin with ARVs. Rifabutin is
expensive; some public health systems do not provide
rifabutin as part of TB treatment and it generally is not
available in resource-limited countries. The U.S. Food
and Drug Administration characterizes rifabutin in
pregnancy category B: it has been safe in animal studies
of pregnancy but has not been proven safe in humans.
For pregnant women who require both TB and ARV
therapy, the use of rifabutin rather than rifampin allows
the use of non-efavirenz-based ARV regimens.
Persons who are already taking ART when TB treatment
is begun should have their ARV regimens reassessed.
The appropriate dosages of rifampin or rifabutin
must be chosen and the ARV regimen may need to be
modified, at least until the completion of TB treatment.
In HIV/TB coinfected patients the optimal timing of
ART initiation in relation to TB therapy is not known.
For patients who are not taking ART at the time
they start TB therapy, many specialists recommend
postponing ART for the first 4-8 weeks of TB therapy.
This strategy decreases the pills burden, adherence
problems, the risk of drug adverse effects, and the risk of
IRS (see below). Some experts recommend that persons
with very low CD4 cell counts (350 cells/µL) may be
best served by completing TB treatment first and then
reassessing the need for ARVs.
Monitoring for efficacy
Ideally, every dosing of anti-TB therapy is observed
and documented by a health care agent or responsible
individual. A member of the health care team should
evaluate patients’ adherence at least weekly during
the initial phase or monthly during the continuation
phase. If gaps in medication use occur, the cause must
be evaluated and a plan to improve adherence must be
implemented.
Section 6—Disease-Specific Treatment | 6–71
During the treatment of pulmonary TB, monthly sputum
specimens should be obtained for smear and culture
until 2 sequential specimens are sterile on culture.
Patients with extrapulmonary and disseminated TB are
usually monitored clinically and with imaging studies.
Biopsies are not repeated but other specimens (cerebrospinal
and other body fluids) may be obtained for
repeat laboratory study including acid-fast bacilli smear
and culture, cell counts, and protein levels. Monitoring
of patients with extrapulmonary and disseminated TB
should be done in consultation with an expert.
Managing immune reconstitution syndrome
Patients in the initial months of treatment for active
TB who begin ART may experience a paradoxical
increase in signs and symptoms of TB (fever, dyspnea,
increased cough, enlarging lymph nodes, worsening
chest x-ray findings, increased inflammation at other
involved sites, or enlargement of central nervous system
tuberculomas). In many cases, this phenomena is caused
by an enhanced immune response against remaining
MTB organisms because of immunologic improvement
from ART. IRS often occurs within 2 weeks up to
several months after ARVs are begun and is usually
accompanied by a sharp decline in the HIV viral load
and at least a 2-fold increase in the CD4 cell count. TB
treatment failure (potentially due to an inappropriate
treatment regimen, inadequate adherence, or drug
resistance) must be ruled out and the possibility of
drug toxicity should be considered. If IRS is diagnosed,
TB and ARV treatment should be continued and
symptoms should be managed with nonsteroidal
anti-inflammatory drugs, or in severe cases, with a
short course of corticosteroids. See chapter Immune
Reconstitution Syndrome.)
Monitoring for toxicity
Antituberculous medications may have significant adverse
effects. Table 4 lists the most important adverse
reactions reported for the commonly used anti-TB
medications. Before initiating TB treatment, check
complete blood count with platelet count, serum creatinine,
liver function tests (aspartate aminotransferase
[AST], alanine aminotransferase [ALT], bilirubin,
alkaline phosphatase), and hepatitis B and C serology.
Newly diagnosed TB patients with unknown HIV status
should be encouraged to undergo testing for HIV infection.
Thereafter, all patients taking TB therapy should
be monitored monthly with a symptom review to assess
possible toxicity.