Page 163 - HIV/AIDS Guidelines

and CAMELIA studies, respectively, and 74% of participants at 2 years in the STRIDE study.

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Mortality rates in patients with MDR or XDR TB and HIV coinfection are very high. Retrospective case control
studies and case series provide growing evidence of better outcomes associated with receipt of ART in such
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coinfected patients, but the optimal timing for initiation of ART is unknown. However, given the high rates and
rapid mortality, most experts recommend that ART be initiated within 2 to 4 weeks after confirmation of the
diagnosis of drug resistance and initiation of second-line TB therapy (BIII).

All HIV-infected pregnant women with active TB should be started on ART as early as feasible, both for
maternal health and to prevent perinatal transmission of HIV (AIII). The choice of ART should be based on
efficacy and safety in pregnancy and take into account potential drug-drug interactions between ARVs and
rifamycins (see Perinatal Guidelines for more detailed discussions). 11
TB meningitis often is associated with severe complications and high mortality rate. In a randomized study
conducted in Vietnam, patients were randomized to immediate ART or to therapy deferred until 2 months
after initiation of TB treatment. A higher rate of severe (Grade 4) adverse events was seen in patients who
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received immediate ART than in those who deferred therapy (80.3% vs. 69.1%, respectively; P = 0.04). In
this study 59.8% of the immediate ART patients and 55.5% of the delayed ART patients died within 9
months. However, in the United States, where patients may be more closely monitored and treated for severe
adverse events such as central nervous system (CNS) IRIS, many experts feel that ART should be initiated as
for other HIV/TB-coinfected patients (CIII).

Drug Interaction Considerations
A rifamycin is a crucial component in treatment of drug-sensitive TB. However, both rifampin and rifabutin
are inducers of the hepatic cytochrome P (CYP) 450 and uridine diphosphate gluconyltransferase (UGT) 1A1
enzymes and are associated with significant interactions with most ARV agents including all PIs, non-
nucleoside reverse transcriptase inhibitors (NNRTIs), maraviroc (MVC), and raltegravir (RAL). Rifampin is
a potent enzyme inducer, leading to accelerated drug clearance and significant reduction in ARV drug
exposure. Despite these interactions, some observational studies suggest that good virologic, immunologic,
and clinical outcomes may be achieved with standard doses of efavirenz (EFV) 13-14 and, to a lesser extent,
nevirapine (NVP) 15-16 when combined with rifampin. However, rifampin is not recommended in combination
with all PIs and the NNRTIs etravirine (ETR) and rilpivirine (RPV). When rifampin is used with MVC or
RAL, increased dosage of the ARV is generally recommended. Rifabutin, a weaker enzyme inducer, is an
alternative to rifampin. Because rifabutin is a substrate of the CYP 450 enzyme system, its metabolism may
be affected by the NNRTI or PI. Tables 14, 15a, 15b, 15d, and 15e outline the magnitude of these interactions
and provide dosing recommendations when rifamycins and selected ARV drugs are used concomitantly. After
determining the drugs and doses to use, clinicians should monitor patients closely to assure good control of
both TB and HIV infections. Suboptimal HIV suppression or suboptimal response to TB treatment should
prompt assessment of drug adherence, subtherapeutic drug levels (consider therapeutic drug monitoring
[TDM]), and acquired drug resistance.

Rifapentine is a long-acting rifamycin that can be given once weekly with INH for the treatment of active or
latent TB infection. Similar to rifampin and rifabutin, rifapentine is also a CYP3A4 inducer. No systematic
study has been performed to assess the magnitude of the enzyme induction effect of rifapentine on the
metabolism of ARV drugs and other concomitant drugs. Significant enzyme induction can result in reduced
ARV drug exposure, which may compromise virologic efficacy. Rifapentine is not recommended for
treatment of latent or active TB infection in patients receiving ART, unless given in the context of a clinical
trial (AIII).

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents J-15

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