Isoniazid preventive therapy for people with HIV

Tuberculosis is the leading cause of death among people with HIV in resource-constrained settings.

Research conducted by the School has shown that isoniazid preventive therapy (IPT), long known to be effective against TB in people who do not have HIV, can also help prevent TB in HIV-positive people, contributing key evidence underpinning World Health Organization (WHO) guidelines.

Professors Alison Grant, John Porter and Peter Godfrey-Faussett have spent many years studying IPT, with Porter conducting trials between 1992 and 1998 to determine the efficacy of isoniazid on the HIV positive population in Kenya and Zambia. The results of the Kenyan trial were inconclusive but the Zambian trial showed that twice-weekly isoniazid for six months reduced the incidence of TB among people with HIV.

Based on these findings, Godfrey-Faussett led the development of new WHO guidelines on IPT use and undertook research on it use in integrated TB and HIV primary care services.

Further research among South African gold miners led by Grant demonstrated the effectiveness of IPT among people with HIV when implemented in routine clinical care. More than 1500 HIV-positive men were included in the study, which found that 300mg of isoniazid daily for six months reduced TB incidence by 38% overall, and by 46% among individuals with no history of TB.

In the Thibela TB trial Grant and Dr Katherine Fielding, with Gavin Churchyard of the Aurum Institute, South Africa and other colleagues, led a cluster-randomised study of community-wide IPT among nearly 80,000 gold miners in South Africa. Prior to enrolment nurses screened participants for active TB and increased risk of isoniazid toxicity. Although the intervention did not reduce TB at population level, key findings were that adverse events due to IPT were extremely rare and nurses could safely administer IPT based on clinical monitoring.

Despite the fact that WHO has been recommending isoniazid since 1998 implementation of the therapy was initially very slow, with only 25,000 HIV-positive people receiving it in 2005. This research has played an important role in promoting IPT uptake, particularly in South Africa. The results were presented at the AIDS 2012 conference in Washington, and in 2013, were published in the New England Journal of Medicine.

Grant and Godfrey-Faussett have been part of WHO IPT guideline development groups, reviewing new scientific evidence and feeding the School’s research into guidelines. New recommendations have included that isoniazid should be offered to individuals regardless of previous TB history, and that people living with HIV should be screened for active TB using a tool which was developed by a team including several School researchers and drawing heavily on School-run studies.