New tuberculosis protocol helps HIV patients

Tuberculosis is the main cause of death among people infected with HIV. According to the World Health Organization (WHO), ten million new cases of tuberculosis were reported worldwide in 2017, and 300,000 deaths by tuberculosis occurred among People Living with HIV/AIDS (PLHA). In this scenario, two measures to reduce the risk of active tuberculosis in this population are extremely important: immediate onset of Combined Antiretroviral Therapy (CART) and Treatment of Latent Tuberculosis Infection (TLTI), a condition in which individuals are infected by tuberculosis but show no signs of active disease. A one-month duration TLTI can be an alternative to the treatment preconized by WHO: isoniazid (INH) for six to nine months – and has the potential to revolutionize the prevention strategy for the tuberculosis/HIV coinfection. The study, whose results were recently published in The New England Journal of Medicine (NEJM), is co-authored by Rodrigo Escada, a researcher in the Laboratory of Clinical Research on STDs and AIDS, at the Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz).

Described in the article One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis, the research took place in the Laboratory of Clinical Research on STDs and AIDS at the INI/Fiocruz and in 44 other centers in 10 countries in Africa, Asia, the Americas and in the Caribbean, following three thousand volunteer subjects with HIV infection. The subjects in the study were randomly distributed to receive either rifapentine and INH for four weeks or INH for nine months, and were later monitored for three years and three months, on average. For Escada, one of the greatest merits of the research was showing that the new strategy is as efficient as the therapy that is currently recommended by WHO. “The patients in the group that used the short-term treatment showed less adverse effects and significantly higher compliance - 97% against 90% in the group that was given INH for 9 months”, he highlights.

Prevention of tuberculosis and other bacterial infections

“People living with HIV/AIDS have up to 27 times higher risk of acquiring tuberculosis than the general population. The treatment of latent tuberculosis infection not only reduces the incidence of the active disease, it also reduces the risk of serious diseases related to HIV,” Escada explains, then emphasizes the importance of talking about the resistance against isoniazid prescription as TLTI. “In 2017, for example, only one million PLHA, from the 30 million eligible for treatment of latent infection worldwide, were given the drug. Lack of faith in the efficiency of the treatment and fear of non-compliance, of toxicity and of interaction with CARTs are the main causes for the low prescription rates of TLTI by physicians”, he complains. For the researcher, a necessary strategy is to raise awareness regarding the adoption of TLTI as early as possible, preferably at the moment of the HIV diagnosis.

In this sense, applying a questionnaire developed by WHO for tracking of active tuberculosis at the moment of triage would be a rapid, simple and effective measure to rule it out, immediately beginning the administration of isoniazid as TLTI for patients with CD4 lymphocyte count (main indicator of immunodeficiency levels in PLHA) lower than 350, even without evidence of latent tuberculosis (i.e. with tuberculin test, known as PPD, negative or untested), as recommended by the Brazilian Ministry of Health. “Patients who show none of the symptoms of active tuberculosis infection can be given INH immediately.  However, it should be emphasized that the questionnaire for tracking of active tuberculosis must be applied to every consultation of PLHA, especially those using isoniazid as treatment for latent tuberculosis, and the need to apply the test should not be ruled out. It is important that the test is done on a yearly basis on patients who have been given INH, if the result is either negative or if the patient was untested and, if the result is positive, the treatment against latent infection should be repeated”, the researcher alerts.

Next steps

The study described did not include pregnant or nursing women, children below 13 years old or people without HIV infection among the volunteer subjects. “In addition, we had few patients with CD4 count below 200, those with a higher risk of presenting more serious forms of tuberculosis. In these cases, we are not able to confirm, at the moment, that the short treatment for latent tuberculosis infection in this protocol is as effective as the one preconized by WHO for these profiles, but new studies are underway”, he concluded.