The World Health Organisation (WHO) is attempting to curb tuberculosis-related deaths in HIV-positive patients by promoting the use of isoniazid preventive therapy (IPT), a prophylactic treatment used to help prevent active TB infection.
Updated guidelines, released by the WHO on World Aids Day on December 1, state that IPT should be used for six months by all children and adults living with HIV, regardless of whether or not they are pregnant, receiving antiretroviral therapy (ART), have previously completed TB treatment, or how sick they are from their HIV infection.
Despite being included in WHO guidelines since 1998 and South African guidelines since 2002, globally only 0.1% of those living with HIV and eligible for IPT had access to the therapy as of this year. Fears over promoting drug-resistant strains of tuberculosis, a constrained public health care sector, limited integration of TB and HIV care, and inadequate training for health workers are all central to low access.
IPT, used since the 1950s, is proven to prevent TB in those who have been exposed to the bacterium or are vulnerable to infection. It is not recommended for those with active TB; they require more comprehensive treatment.
TB remains the number one killer of people living with HIV, with 70% of TB patients co-infected with the virus. Because of their weakened immune systems, people living with HIV are up to 37 times more likely to be infected with TB than those who are not. One-quarter of HIV-positive people will die of TB. South Africa has some of the highest rates of both in the world.
Treat first, test later
Given the large number of deaths associated with TB and HIV co-infection, coupled with difficulties in testing for the bacterium within resource-constrained settings, the updated WHO recommendations suggest that people living with HIV in countries with high infection rates such as South Africa do not need to be tested for TB before receiving prophylactic treatment, but instead can be assessed by health workers based on whether they have a cough, fever, night sweats and/or weight loss.
In the absence of these symptoms, active TB is unlikely and patients should begin six months of IPT. If possible, tuberculin skin tests should be used in addition to symptom screening, but it is not a requirement.
Inability to test for active TB prior to IPT initiation has been cited as a major barrier worldwide, and particularly in South Africa, given the large HIV-TB caseload and low access to health care. The WHO has called for research to consider the potential effects of accidentally administering IPT to a person with undiagnosed active TB.
The organisation’s updated guidelines also reflect South African research indicating that the therapy should be given to those on ART, which has not been recommended previously. A study released in November by the Consortium to Respond Effectively to the Aids/TB Epidemic (Create) showed that IPT use in those newly initiated on ART reduced mortality by 50%.
The study observed 3 270 gold miners living with HIV and showed that those who started IPT at the same time as ART had less advanced HIV disease, higher CD4 counts (a marker of immune response) a lower viral load, and higher levels of hemoglobin, a protein that enables red blood cells to carry oxygen through the body.
IPT and ART go together
According to Gavin Churchyard, executive director of the Aurum Institute for Health Research and one of the study authors: “ART in itself [leads to] a major reduction in death, and adding IPT on that reduces it further — we already knew that IPT with ART reduces the risk of TB, [but] this is the first time that anybody has shown that it reduces mortality.
“This has profound public health implications. We have a drug that is readily available and is cheap, safe and effective. It must be used on a much wider scale.”
In addition to the new WHO recommendations, updated South African guidelines released in June of this year no longer discourage IPT for those receiving ART.
Both the WHO guidelines and Create research point to widespread misconceptions about resistance and side effects associated with IPT, as well as the medication’s effectiveness. Another Create study released in November notes that clinicians are often unwilling to prescribe IPT despite it being recommended by the WHO and included in national guidelines, primarily because of fear of promoting drug-resistant TB.
The authors of the study note: “The primary barrier for IPT implementation is lack of knowledge and experience of — healthcare providers. Prescribers [are] unaware of the benefits of IPT and unclear about guidelines. In addition to overcoming operational barriers, a change in healthcare-worker perception is needed. Prescribers should be made aware of the consensus from current literature that IPT does not promote — resistance.”
Few side effects from IPT
Another Create study adds to a wealth of evidence that fears of IPT adversely impacting patients are largely unfounded. The study, released in November, shows that side effects from IPT use are generally mild and occur in a small percentage of the population: of 24 221 individuals enrolled, only 130, or 0.54%, had adverse side effects, primarily rash, peripheral neuropathy (nerve damage), clinical hepatotoxicity (liver damage) and convulsions.
In contrast, 62.6% of the population reported feeling “much better” after starting IPT, with a majority citing increased appetite after a month of treatment as the major side effect. One death resulted from side effects, or .004% of the study population. The authors state: “Clinical criteria can be established to screen patients for serious toxicity risks and safely monitor patients while they are on IPT.”
According to Churchyard, a patient-empowered approach, matched with nurse-initiated IPT and increased training for clinicians, is needed to ensure that IPT reaches a wider population.
“We need to make [doctors] accountable to the patients. Patients should be — saying ‘we want this intervention. We’ve been told by the WHO that it’s been safe — we want this — and you have to give this to us’. People are denying interventions [that] are effective and safe. We have to do a much better job.”