Abstract
Tuberculosis remains the leading killer of people living with HIV (PLHIV) and HIV greatly increases the risk of reactivation tuberculosis (100 fold). Although tuberculosis prophylaxis therapy (TPT) could prevent TB reactivation in 60-90% but current regimen (INH 9 months:9H) is limited by poor implementation and low completion rate due to long duration, fear of INH resistance and dormant TB could not be killed by INH. We evaluated the safety and efficacy of a novel shorter TPT in Thailand, a high TB/HIV burden country. Methods: PLHIV on ART > 2 weeks and free of active TB are randomized to Arm A: 1 HP (isoniazid 300 mg plus rifapentine 450-600 mg once daily for 4 weeks) or Arm B: 3HP (isoniazid 700-900 mg plus rifapentine 750-900 mg once weekly for 12 weeks) from 14 hospitals in Thailand. The participants will be followed up for 3 years. The primary end point was the first diagnosis of TB or death from TB or unknown cause. This study is ongoing, plan to enroll 2500 PLHIV. However, it is affected by COVID 19 pandemic and also impurified of rifapentine. By the way, the impurified of the study drug has been approved from the US FDA that it has a few impurification so it causes a few effects to the develop cancer. This analysis is focused on 1st year with 644 PLHIV enrolled. Results: A total of 644 patients (86% male) were enrolled, 322 each were assigned to Arm A or Arm B. Median age was 30 (IQR 25-39) years, median baseline CD4 cells counts were 300 (201-415) cells/mm3, and 24% of them had baseline CD4< 200 cells/mm3. All received FDC of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/efavirenz (EFV) for a median 1.3 months. The median duration of follow-up was 1 year at the study entry. There were no active TB or death reported. Adverse event occurred 6.1% (Arm A = 6.5% and Arm B = 5.6%) as following hepatitis (elevated ALT) (Arm A=3.1% and Arm B 4%). Majority of hepatitis were asymptomatic cases, it was found during schedule blood testing. Rash occurred 0.8% (Arm A=1.2% and Arm B 0.3%). 1 case (Arm A) had numbness of feet. Serious side effect occurred among 10 cases (Arm A=0.9% and Arm B 2.1%. Totally 2 cases developed hypersensitivity reaction (rash and hepatitis), both of them were in Arm B. The percentage of treatment completion was 93.2% and 91.6% in Arm A and Arm B, respectively. At 48 weeks after starting TB drugs, 96% and 95.7% of Arm A and Arm B had HIV RNA <50 copies/ml, respectively. Conclusion: In the treatment of latent tuberculosis infection, both Arm A and Arm B resulted in better adherence, low percentage of discontinued treatments and highly efficacy to prevent active TB. No active TB or death were reported during 1 year.
