Weekly isoniazid (900mg) and rifapentine (900mg) for 12 weeks (3HP) has similar efficacy to 6 months of daily isoniazid (6H) as TB preventive therapy. We compared treatment completion rates and effectiveness of 3HP vs. 6H and the effectiveness of 3HP given annually vs. once among HIV-positive people. (NCT02980016)
HIV-positive people in South Africa, Ethiopia and Mozambique aged ≥2 years, without active TB and on antiretroviral therapy (ART) for ≥3 months or ineligible were randomized 9:9:2 to periodic (annual) 3HP (p3HP), 3HP, or 6H. Participants in the 3HP/p3HP and 6H arms were followed for 24 and 12months, respectively; all were seen monthly for the first three months of each participation year. Medication doses were directly observed at dispensing visits and otherwise self-administered. Participants in the 6H arm were dispensed 3 months treatment at month 3. Participants were screened for TB with symptoms, chest X-ray and sputum culture after 12 and 24 months. Completion of the initial treatment course in the combined 3HP/p3HP arms vs. 6H was compared using pill counts. TB incidence and all-cause mortality over 12 months was compared in the 3HP and 6H arms, and TB incidence, all-cause mortality, and permanent discontinuation of 3HP for adverse events over 24 months was compared in the p3HP and 3HP arms.
Between November 2016 and November 2017, 4593 participants were screened, 4027 enrolled and 4014 analysed. The median age was 41 years (19 (0.5%) <18 years), all were on ART, 70% were female, 38% were QuantiFERON-TB GOLD Plus positive; 63%, 22% and 15% were from South Africa, Ethiopia and Mozambique, respectively. Treatment completion in the combined 3HP (n=3610) and 6H (n=404) arms was 90.4% versus 50.5% (risk ratio: 1.79; 95%CI:1.62-1.79). TB incidence and mortality by study arm are shown in the table. TB incidence and mortality from month 0 to month 12 was similar in the 3HP and 6H arms. TB incidence over 24 months and from month 12 to month 24 was similar in the p3HP (n=1808) and 3HP (n=1802) arms. Over 24 months, TB incidence among QuantiFERON Plus positive participants, incidence of rifampicin resistant TB, and mortality were similar in the p3HP and 3HP arms. Treatment discontinuation in the p3HP and 3HP arms was 1.2% vs. 0.6% (OR2.11, 95%CI:0.95-5.02).
Treatment completion was higher in the 3HP arms vs. 6H. In high TB transmission settings, annual 3HP did not provide additional benefit to people receiving ART.