When plagues collide

Individually, unchecked HIV and Mycobacterium tuberculosis are sufficient to cripple whole communities, eroding society at many levels. Together, they represent epidemics of huge proportion, as Professor Gary Maartens outlined in his inaugural lecture last week, When Plagues Collide: HIV and Tuberculosis.

Maartens is surprisingly upbeat for someone who works at the interface of these diseases where tuberculosis accelerates the progression of HIV and the patient's risk of developing a new AIDS illness by as much as 60%.

But he finds the field "exciting and fascinating". Appointed to the Chair of Clinical Pharmacology in 2004, succeeding Professor Peter Folb, Maartens is a dyed in the wool researcher.

He and collaborator Dick Chaisson of the John Hopkins University in Baltimore were recently awarded an R01 grant by the National Institutes of Health. They are working to understand the adherence by HIV-positive patients to their medication, using Direct Observed Therapy (DOT), with the aid of patient-nominated sponsors.

His inaugural lecture, however, gave a tour of HIV and TB from a broader, more personal perspective.

"TB has always been a very common problem for Africans and was the leading cause of death on the continent, even before HIV entered the picture."

Tuberculosis levels were pretty much under control until a surge in the 1980s. By the 1990s, rates were climbing, particularly in eastern and southern Africa. Now, the rates are soaring, mainly due to the rise of HIV.

"In South Africa, the case load has increased three to six fold, a difficult situation when the country's health care professionals are leaving in droves and the system is overburdened," Maartens said.

Over six million South Africans are infected with HIV and the risk of getting TB grows exponentially as the immune system declines.

The HIV pandemic presents a massive challenge to global TB control. Not only does HIV increase the risk of reactivating latent tuberculosis infection, it also increases the risk of rapid TB progression soon after infection or reinfection.

"This epidemic is not confined to short-lived outbreaks, like the Marburg virus, or haemorrhagic fever, in a north Angolan town. It is not something that is measured in months but in years," Maartens reflected.

A Medical Research Council study published in 2003 showed 63% of patients with TB were infected with HIV. This figure was over 80% in KwaZulu-Natal and 30% to 40% in the Western Cape.

The mortality of untreated HIV-associated TB is very high, with many patients dying within a few months.

The HIV/TB interface also makes TB more difficult to diagnose. Usually, a simple and inexpensive sputum test would suffice. But with the HI virus playing havoc with the immune system, the results sometimes come up negative. And with HIV, the pace at which TB symptoms develop is faster.

In a normal picture, 2 to 3% of patients develop primary TB after being exposed to bacteria. Most people, around 97%, have what is called latent TB infection; we've been exposed to the virus but we don't develop symptoms. Seven percent of people have what is called reactivation TB.

With HIV, the collision factor between the plagues becomes startlingly evident. Primary infection rates rise to 30%. The 7% lifetime risk becomes an annual 10% risk, compounding the picture.

To complicate things, anti retroviral and TB treatments interfere with one another, affecting the way the body metabolises drugs.

"Anti retrovirals are broken down very quickly in the body, which results in the patient absorbing a low level of the drug."

There is also the complication of shared toxicity between the drugs used to treat TB and HIV. Some drugs interact, reducing efficacy and resulting in reduced drug activity.

"To make life fun, some can induce activity, others can reduce it," Maartens added.

People with HIV are also at high risk of dying from other opportunistic infections during the six to eight months of TB treatment.

"They die with TB rather than from TB," Maartens commented.

But there is no doubting the efficacy of anti retrovirals, which make the biggest impact among patients with HIV.

"A Khayelitsha community study showed that a regimen of anti retrovirals reduced the incidence of TB in HIV-positive patients by 59%."

The magic word, however, is adherence.

"Adherence is important in all therapies, but even more so with anti retrovirals. Anything below an 80% adherence rate spells bad news and even deaths through TB," Maartens noted.

Plagues and medication aside, there are also peculiar human factors at play in the treatment of TB and HIV. Health care workers, Maartens explained, belonged to different camps, embodying markedly different "cultures".

"The health care workers dealing with TB tend to be very community-oriented. It's a system based on nursing care, a culture very resistant to change. For HIV, health care is based on a greater component of individual care. It is patient-centred, focused on human rights, with lots of drugs and regimens, and characterised by rapid treatment changes.

"We have a long way to go before the two cultures can meet to stop the epidemics clashing."

(The next inaugural lectures will be presented by Professor Richard Hift of the Clinical Skins Centre on September 21, and Professor Raj Ramesar, Department of Clinical Laboratory Sciences in the Division of Human Genetics, on September 28.)