People Living With HIV (PLWH) are at high risk of active tuberculosis (TB). Guidelines both domestically and internationally suggest that PLWH with positive latent tuberculosis infection (LTBI) screening and those with a history of close contact with active TB should receive TB preventive treatment. However, commonly used preventive treatment regimens such as rifampin and rifapentine have potential drug interactions with HIV antiretroviral therapy (ART). A multi-center retrospective study from Taiwan, China, presented at the 12th International AIDS Society HIV Science Conference (IAS 2023) showed that ART based on integrase inhibitors (INSTIs) combined with rifapentine-based short-course TB preventive treatment does not affect the patient’s sustained HIV virologic suppression rate.
01
LTBI preventive treatment for HIV patients
Human Immunodeficiency Virus (HIV) infection is a high-risk factor for active TB. Co-infection of HIV and Mycobacterium tuberculosis (MTB) is considered a “deadly human syndrome.” Despite the significant progress in HIV antiretroviral therapy (ART), TB remains the most common cause of HIV-related deaths, with about one-third of AIDS patients dying from TB.
Domestic and international guidelines recommend TB preventive treatment for PLWH with positive LTBI screening and those with a history of close contact with active TB. Among these, the short-term preventive regimen of 3-month isoniazid/rifapentine combination (3HP) or the ultra-short-term regimen of 1 month (1HP) have shown higher completion rates. However, for PLWH who are on ART, attention should be paid to drug interactions (DDI) of rifamycin drugs like rifampin or rifapentine with ART. This is because rifamycins are strong inducers of hepatic enzyme P450 and interact with protease inhibitors (PIs) and non-nucleoside drugs (NNRTIs), and therefore should not be used in such ART-treated patients. Currently, there are few studies on the drug interaction between rifapentine and ART. WHO guidelines for LTBI management do not recommend the use of rifapentine-containing regimens for patients receiving dolutegravir (an INSTI).
02
Multi-center retrospective study from Taiwan，China
To evaluate the efficacy and safety of rifapentine-based short-course TB preventive treatment in PLWH on INSTI-based ART, this study retrospectively analyzed PLWH from August 2019 to October 2022 with positive or suspicious γ-interferon release assay (IGRA) results and excluded active TB. They received either 3HP or 1HP preventive treatment in combination with INSTI-based ART. The primary outcome was the sustained virologic suppression rate (PVL < 200 copies/mL) 3-6 months after LTBI treatment.
The study included 456 PLWH. Most were male (94.3%), with a median age of 43 years, 91.9% received INSTI-based ART, a median CD4 cell count of 651 cells/mm3, and 97.6% achieved PVL < 200 copies/mL. Among the PLWH on INSTI-based ART:
– 1HP/BIC group (1HP combined with bictegravir): 142 cases;
– 1HP/DTG group (1HP combined with dolutegravir): 46 cases;
– 3HP/BIC group (3HP combined with bictegravir): 28 cases;
– 3HP/DTG group (3HP combined with dolutegravir): 203 cases.
In the per-protocol (PP) population, the sustained virologic suppression rates of the four study groups were:
– 1HP/BIC group: 100% (125/125);
– 1HP/DTG group: 100% (44/44);
– 3HP/BIC group: 100% (17/17);
– 3HP/DTG group: 96.7% (178/184).
Completion rates were similar between the 1HP and 3HP groups (92.7% vs 90.0%). No PLWH stopped using INSTI-based ART before combination with rifapentine-based LTBI preventive treatment. The incidence of adverse events (AE) of any grade was also similar between the 1HP and 3HP groups (60.9% vs 57.4%), with most being Grade 1 (40.1%) or Grade 2 (13.4%) AEs. Although flu-like symptoms were the most commonly reported AE (40.1%), the 1HP group observed more skin-related AEs (17.8% vs 9.6%) compared to the 3HP group.
The results of this retrospective study indicate that ART regimens containing INSTIs combined with rifapentine-based short-course TB preventive treatment have good safety and maintain a high viral suppression rate.
▌References:
[1]Kuan-Yin Lin, et al. IAS 2023;
[4]Yang Qingluan, Ruan Qiaoling, Zhang Wenhong. Clinical Journal of Internal Medicine, 2019;
[3]Chinese Anti-Tuberculosis Association, 2021.
