NEW YORK (Reuters Health) – Tuberculosis preventive therapy (TBT) completion rates were higher for short-course isoniazid-rifapentine than for isoniazid alone among individuals with HIV on antiretroviral therapy (ART) in Africa, a randomized trial shows.
Further, repeating the annual short-course treatment did not improve efficacy.
As reported in the Annals of Internal Medicine, Dr. Gavin Churchyard of the Aurum Institute in Houghton, South Africa and colleagues randomized 4,104 individuals with HIV infection on ART without active TB (median age, 41; 69.5% women) to one of three preventive treatment groups: weekly rifapentine-isoniazid for 3 months (3HP), given annually once; the same treatment given annually twice; or daily isoniazid for 6 months.
Participants were screened for TB symptoms at baseline, 3 months and 12 months of each of the two study years, and at 12 and 24 months with chest radiography and sputum culture.
Pill counts were used to assess treatment completion.
At 12 months, treatment completion was 90.4% for rifapentine-isoniazid versus 50.5% for isoniazid alone (risk ratio, 1.78).
TB incidence was similar among participants receiving rifapentine-isoniazid twice or once (hazard ratio, 0.96).
The authors state, “If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness.”
Drs. Rebecca Berhanu and Karen Jacobson, both of Boston University and coauthors of a related editorial, commented on the study in an email to Reuters Health. They note that while there was no difference in TB incidence at 24 months with 3HP given once or twice, there also “was no difference in TB incidence at 12 months between the IPT and 3HP arms (1.12 versus 1.74/100 person years; HR 1.60), despite the much lower completion rates of IPT than 3HP.”
Possible reasons for the lack of effect, they say, include:
– TB incidence is dropping in the region overall and was lower than anticipated in the trial, leading to potential underpowering. “This lower disease rate mirrors the drop in HIV-associated TB seen in sub-Saharan Africa in the past decade, largely driven by increasing ART coverage and a marker of the success and maturity of ART treatment programs”;
– Missed subclinical TB at baseline that was not identified by symptom screen but detected at 12 months when all participants submitted a sputum for TB culture; and
– Trial participants were ART-experienced (median of > 4 years of ART) with relatively high CD4 counts (median 446-471 cells/microliter in the three arms). “Perhaps the effect of prolonged or repeated TPT is limited to people newly initiating ART? This was not seen in the subgroup analysis, but the trial was not powered to answer this question,” they note.
“TB reinfection will occur and may require repeat TPT, but that may not be for several years in ART-experienced populations,” Drs. Berhanu and Jacobson conclude.
SOURCE: https://bit.ly/3kgXxAy and https://bit.ly/3kiVb43 Annals of Internal Medicine, online August 23, 2021.
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