Page 161 - HIV/AIDS Guidelines

HIV disease. It may be associated with a higher HIV viral load and more rapid progression of HIV disease. 3

Active pulmonary or extrapulmonary TB disease requires prompt initiation of TB treatment. The treatment of
active TB disease in HIV-infected patients should follow the general principles guiding treatment for
individuals without HIV (AI). Treatment of drug-susceptible TB disease should include a standard regimen
that consists of isoniazid (INH) + a rifamycin (rifampin or rifabutin) + pyrazinamide + ethambutol given for
4
2 months, followed by INH + a rifamycin for 4 to 7 months. The Guidelines for Prevention and Treatment of
4
Opportunistic Infections in HIV-Infected Adults and Adolescents include a more complete discussion of the
diagnosis and treatment of TB disease in HIV-infected patients.

All patients with HIV/TB disease should be treated with ART (AI). Important issues related to the use of
ART in patients with active TB disease include: (1) when to start ART, (2) significant pharmacokinetic drug-
drug interactions between rifamycins and some antiretroviral (ARV) agents, (3) the additive toxicities
associated with concomitant ARV and TB drug use, (4) the development of TB-associated IRIS after ART
initiation, and (5) the need for treatment support including DOT and the integration of HIV and TB care and
treatment.

Antiretroviral Therapy in Patients with Active Tuberculosis
Patients Diagnosed with Tuberculosis While Receiving Antiretroviral Therapy

When TB is diagnosed in a patient receiving ART, the patient’s ARV regimen should be assessed with
particular attention to potential pharmacokinetic interactions with rifamycins (discussed below). The
patient’s regimen may need to be modified to permit use of the optimal TB treatment regimen (see Tables
14–16 for dosing recommendations).

Patients Not Yet Receiving Antiretroviral Therapy

Until recently, when to start ART in patients with active TB has been a subject of debate. Survival is
improved when ART is started early following initiation of TB therapy, but a delay in initiating ART often
was favored because of the potential complications of high pill burden, additive toxicities, drug interactions,
adherence, and the potential for development of IRIS.Recent studies primarily conducted in resource-limited
settings, including three randomized controlled trials, have helped clarify the question of when to start ART
in patients with active TB. 5-8
The SAPiT study conducted in South Africa convincingly demonstrated that starting ART during rather than
after concluding treatment for TB can significantly reduce mortality. In this study, ambulatory HIV-infected
3
patients with smear-positive TB and CD4 counts <500 cells/mm were randomized to one of three treatment
arms: integrated therapy with ART initiated either during the first 4 weeks of TB therapy or after the first 8
weeks of TB treatment (i.e., during the continuation phase of TB therapy) or sequential therapy with ART
initiated after the conclusion of standard TB therapy. The median CD4 cell count of participants at study
3
entry was 150 cells/mm . The sequential therapy arm was stopped when an early analysis demonstrated that
the mortality rate in the combined two integrated arms was 56% lower than the rate in the sequential therapy
arm. Treatment was continued in the two integrated arms until study completion. 5
With the completion of SAPiT and 2 other randomized controlled trials, CAMELIA and STRIDE, the question
on the optimal time to initiate ART during TB therapy has been addressed. Findings from these trials now serve
as the basis for the Panel’s recommendations on when to start ART in patients with active TB.

In the final analysis of the SAPiT trial, there were no differences in rates of AIDS or death between the 2
integrated arms of the study (patients who started ART within 4 weeks after initiating TB treatment vs. those
who started ART at 8–12 weeks [i.e., within 4 weeks after completing the intensive phase of TB treatment]).

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents J-13

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