In HIV/TB Co-infection, Initiate Antiretroviral Therapy Early

PHILADELPHIA, PA—Earlier initiation of antiretroviral therapy (ART) significantly lowered mortality in patients with HIV and tuberculosis (TB) co-infection, despite a higher incidence of immune reconstitution inflammatory syndrome (IRIS), according to data presented at IDWeek 2014.

Integrating ART and TB therapy can improve patient outcomes; however, what remains unclear is when ART should be initiated during treatment of active TB, which is the most common cause of mortality in those with HIV.

To determine whether optimal timing exists, Maryam Mahmood, MD, of the Internal Medicine Department, Reading Hospital, West Reading, PA, conducted a systematic review and meta-analysis to “compare the actual risks and benefits of early combined therapy balanced against the pooled risk of medication changes, IRIS, and death.”

Six randomized controlled trials of 2,303 adolescent and adult patients co-infected with HIV and TB were identified from 36 sites in 4 different continents. The trials compared early (within 4 weeks) vs. later (8–12 weeks) initiation of ART during TB therapy. Of the population studied, 62% were male and pulmonary TB was the most common site of infection. 

The primary outcome measure was all-cause mortality at 48 weeks; secondary outcomes were IRIS incidence, serious adverse effects (SAEs, including ART regimen change), HIV viral load, and mycobacterial clearance.

Dr. Mahmood found that compared with 8–12 weeks, initiation of ART within 4 weeks was associated with a non-significant decrease in overall mortality at 48 weeks (relative risk [RR] 0.81, 95% confidence interval [CI] 0.63–1.05; P=0.11). Specifically, earlier initiation of ART in patients with a CD4 count <50 cells/µL was associated with a 43% lower risk of mortality or developing a new AIDs-defining illness (RR 0.57; 95% CI 0.38–0.86; P=0.008), she reported.

There was, however, a twofold increase in risk of IRIS associated with early initiation of ART (RR 2.21, 95% CI 1.79–2.23; P>0.001). “Median time to development of IRIS ranged from 14 to 44 days, with no difference between the earlier and later ART groups,” Dr. Mahmood said.

Incidence of overall non-IRIS SAEs were similar, regardless of timing of ART initiation, which also did not affect the number of patients with a viral load of <400 copies/mL at 48 weeks or successful outcomes of TB therapy.

“These findings strengthen the evidence for early initiation of ART in HIV-associated pulmonary TB, particularly in those with advanced immune suppression,” Dr. Mahmood noted. What is needed next are studies to assess specific barriers to adapting integrated HIV/TB care and rapid initiation of ART so that they become routine clinical practice.