Tuberculosis (TB) preventive treatment reduced the risk of developing active TB by 61% in people with HIV starting antiretroviral treatment, a large six-country study has found.
The study findings, published this month in The Lancet HIV, show that tuberculosis preventive treatment remains an essential element of HIV care in the era of universal antiretroviral treatment, say the study investigators.
Tuberculosis is a common opportunistic infection in people with HIV. A meta-analysis of studies carried out in sub-Saharan Africa between 2000 and 2022 estimated that approximately four in every hundred people with HIV develop TB each year. The study found that antiretroviral therapy reduced but did not eliminate the risk of developing TB.
Antiretroviral therapy improves immunity but TB-specific preventive treatment is needed to protect against the development of TB.
Tuberculosis preventive treatment (TPT) consists of a course of medication that clears latent TB infection. Tuberculosis bacteria can remain in the body, controlled by the immune system for many years after exposure, until a decline in immunity or malnutrition allows the development of active tuberculosis. People with HIV who have been exposed to TB and have a latent infection are especially vulnerable to the development of active tuberculosis.
The World Health Organization strongly recommends either a 6-month or 9-month course of isoniazid, or a 3-month course of isoniazid paired with rifapentine or rifampicin, as TB preventive treatment for all people with HIV. TPT should be started as soon as possible after entry into HIV care, once active TB has been ruled out.
Although clinical trials show that TPT reduced the incidence of tuberculosis by 32% - 62% depending on the population studied, all of these studies were carried out before universal HIV treatment became the standard of care. How much TPT reduces TB incidence in people receiving antiretroviral treatment was unclear.
To answer this question, an international research group devised a prospective cohort study to emulate a clinical trial. The study was designed to assess the effectiveness of TPT when initiated within eight weeks of starting antiretroviral treatment.
The study used data from electronic medical records in people with HIV starting antiretroviral treatment in six countries where the incidence of TB is high (Haiti, Kenya, Nigeria, Uganda, Ukraine and Zimbabwe). People starting treatment between January 2018 and December 2021 (December 2022 in Uganda and Zimbabwe) were eligible for inclusion in the study. Participants were followed for two years after TPT initiation, or until death or a diagnosis of active TB.
Glossary
active TB
Active disease caused by Mycobacterium tuberculosis, as evidenced by a confirmatory culture, or, in the absence of culture, suggestive clinical symptoms.
HIV
Human immunodeficiency virus, the virus which causes AIDS. There are two variants: HIV-1, and HIV-2. HIV-1 is by far the most common worldwide. See ‘subtype’ for more information.
incidence
The proportion of people who acquire an infection or develop a condition during a specified period of time. Incidence reflects newly acquired infections and conditions. See also ‘prevalence’.
on
Abbreviation of a Latin term meaning every night.
risk
Researchers used different methods to select the study population for each country, depending on national record-keeping systems and the number of people with HIV starting treatment. Whereas everyone starting treatment in Haiti (n=69,936) and Ukraine (n=57,851) was included in the study, researchers selected nationally representative samples in Nigeria (n=8,053), Uganda (65,936) and Zimbabwe (24,099). In Kenya (n=9,549), everyone receiving treatment through one PEPFAR implementing partner was included.
Overall, 56% of study participants in the six participating countries were female, 62% were aged 25-44 years, 44% had WHO stage 1 HIV (asymptomatic) and 59% took dolutegravir-based antiretroviral treatment. Study populations varied somewhat between countries in their demographic composition, reflecting differences in the HIV epidemics of the participating countries. The Ukrainian cohort had a higher proportion of male participants than others, and participants in Ukraine were more likely to be over 35 years old than in other countries. There were also differences between countries in HIV treatment regimen (participants in Haiti, Kenya and Nigeria were more likely to receive dolutegravir and less likely to receive efavirenz than participants in other countries). Approximately 40% of participants in Uganda and Ukraine did not receive TPT, compared with less than 6% in Nigeria.
The primary outcomes of the study were the incidence of tuberculosis (laboratory confirmed or clinically diagnosed), and death from any cause.
A pooled analysis of cohorts from all participating countries showed that starting TPT within eight weeks of antiretroviral therapy initiation reduced the risk of TB by 61% (adjusted hazard ratio 0.39, 0.34-0.43) and the risk of death by 45% (aHR 0.55, 0.51-0.58). TPT was associated with a reduced risk of TB and death for all countries apart from Nigeria, where the difference in outcomes was non-significant owing to the small sample size.
Demographic and HIV-related factors had negligible impact on the effectiveness of TPT in preventing TB, with the exception of enrolment year in Kenya.
Starting TPT within two weeks of initiating antiretroviral treatment improved the protective effect of TPT compared with starting within eight weeks, reducing the risk of developing TB by 68% in a pooled analysis.
The study investigators point out that TPT use was not widespread until PEPFAR committed to providing it for everyone in 2018. By 2023, 13 million had received TPT through PEPFAR-funded programmes. As funding for HIV care becomes constrained, “continued vigilance for TPT delivery to people with HIV will be crucial to ensure gains are sustained,” they conclude.
Supply chain management, integration of TPT into HIV care, improved access to point-of-care diagnostics for TB such as urinary TB-LAM, and education for professionals and stakeholders will continue to be critical for programme implementation. Further evidence on short TPT regimens will also aid implementation, the authors conclude.
References
Shah NS et al. Programmatic effectiveness of tuberculosis preventive treatment for people with HIV in six high-tuberculosis burden countries (PROTECT): a prospective cohort study and meta-analysis. Lancet HIV 13: e723-e734, 2026 (open access).
https://doi.org/10.1016/S2352-3018(26)00140-2
Full image credit: Loyce prepares her weekly pill box of Anti-Retroviral Treatment at her home in Chitungwiza. Morgana Wingard/Global Fund Advocates Network. Image available at the Global Fund under a Creative Commons licence CC BY-NC 4.0.
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