Diagnoses and treatment not keeping up with HIV/TB co-epidemic

Issue: December 2007

With rates of HIV/tuberculosis co-infection skyrocketing in sub-Saharan Africa, the Forum for Collaborative HIV Research recently released a report assessing the threat of the co-epidemic and the research needed to combat it. The report found that health systems are currently underfunded and ill-prepared to diagnose, treat and prevent the spread of HIV/TB.

“The overall message is that the HIV community has to start taking TB seriously, both in its research programs – which include clinical, operational and implementational research – as well as in the actual programs on the ground,” said Veronica Miller, PhD, executive director of the Forum for Collaborative HIV Research. “It is getting out of control, and unless the HIV community starts focusing in on this, we will be missing some opportunities for improving the situation.”

Scope of the co-epidemic

The need to focus on the HIV/TB co-epidemic is underscored by some startling numbers. According to the Forum’s report, WHO reported 8.8 million new cases of TB and 1.6 million TB-related deaths in 2005. Of those, 195,000 were in HIV-infected patients. In southern and eastern Africa today, at least 50% of new TB cases occur in HIV-infected patients. Rates of TB in children in the region have also been on the rise, with one South African study indicating that 23.4 of every 100 HIV-infected children develop TB every year.

Further complicating the issue are rising rates of both multidrug resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Although XDR-TB was confirmed in 17 countries in March 2006, the number rose to 41 countries as of October 2007. Estimates for MDR-TB and XDR-TB stand at 400,000 and 26,000 patients, respectively, but the Forum’s report stresses that sub-Saharan Africa and parts of Southeast Asia are underrepresented in these numbers. According to the report, “the emergence of resistant TB has also uncovered significant gaps in TB control strategies that threaten the future success of both TB and HIV programs.”

The combination of drug-resistant TB and HIV has proven to be potent. “The mortality rate from XDR-TB in combination with HIV is staggering, with more than 80% of patients dying rapidly,” Richard Chaisson, MD, said in a press release. “Despite the urgency and severity of the problem, we have neither the drug testing nor the surveillance tools in place to know the full extent of XDR-TB and HIV across large areas of Africa.” Chaisson is the director of CREATE (Consortium to Respond Effectively to the AIDS-TB Epidemic) and a professor at the Johns Hopkins Center for Global Health.

Areas of research

Regarding to research programs, Miller said the most important point now is to encourage collaboration between TB and HIV researchers. “In many situations the programs are separate streams,” she told Infectious Disease News. “You have the TB people and you have the HIV people, and they are not necessarily linked together.”

The report indicated that development of new diagnostic methods is among the top research priorities. Existing diagnostic tests for TB are antiquated and have low sensitivity, and many high-prevalence settings lack adequate laboratory capacity and the capability to detect drug resistant TB. Also, standard smear microscopy diagnostic testing has limited utility among patients with HIV; smear-negative pulmonary TB ranges from 24% to 61%. “In many African countries, although it might be possible to diagnose HIV within an hour using a rapid test, it typically takes three weeks to obtain a diagnosis from a sputum smear or a sputum culture,” the researchers wrote. “During that time, people with active TB, including MDR- and XDR-TB, may unknowingly continue to spread their infection.”

Another important area of research is epidemiology. Although the numbers that are known are disturbing, Miller said that epidemiological predictions for TB and HIV/TB co-infection are not yet known. Mapping of hotspots using procedures appropriate for outbreaks could lead to a better understanding of the true severity of the problem.

Infection control

One of the most prominent ways drug resistant TB spreads among patients with HIV is via nosocomial infection, and limiting this problem in antiretroviral therapy programs is crucial. “If you have an HIV-positive person going to a clinic to get their HIV drugs and doing everything they are supposed to do to take care of their HIV, and in the waiting room at the clinic you have someone with drug-resistant TB, then the other patients are at risk for catching it,” Miller said. “This is simply because of the lack of infrastructure in terms of dealing with TB.”

Finally, optimal treatments for HIV/TB co-infection have yet to be determined as well. There is strong evidence that isoniazid preventive therapy (IPT) combined with optimal ART is effective in latent TB infection, but among high burden countries in Africa only Botswana has adopted IPT at the national level. “A priority in this area is to address the exclusion of active TB before initiation of IPT to avoid suboptimal treatment of active TB that could lead to drug resistance,” the researchers wrote.

Research into TB drugs has moved at a relatively slow pace to this point, according to Miller, with drug trials failing to focus in on areas that need the most help. “As new TB drugs are developed, they need to be tested in patients with drug resistant TB much more quickly,” she said. “They need to be tested in HIV/TB co-infected people rather than just in treatment-naive TB patients in the western world.”

HIV/TB in children

All of these research needs are perhaps even more urgent in children with HIV/TB co-infection, as previous work has generally ignored this growing population. As in adults, TB exacerbates HIV-related mortality in children, and children who have HIV, but are not on ART show poor responses to TB therapy. The researchers noted that diagnosis of TB remains difficult in immunocompromised children, and optimal treatment has yet to be determined. “Nearly every infant with HIV suffers from pneumonia,” Mark Cotton, MD, said in a press release. “TB also causes acute pneumonia, but with our current tools it is hard to know what is and is not caused by TB. Children should be included in trials to evaluate new anti-TB drugs.” Cotton is a pediatrician and HIV researcher at Stellenbosch University in South Africa.

With all of these research needs and a need to combine the two previously distinct fields of HIV and TB research, putting funding and resources in the right hands is also an important issue. “We need ways to implement the two programs in such a way that they synergize with each other rather than making one or the other field feel threatened,” Miller said.

It has become clear that improved research programs and infection control are crucial in stemming the HIV/TB co-epidemic. “I think it can be reversed, but it will require rapid action in terms of the diagnostic infrastructure,” Miller said. “The sad part is that although TB was a problem previously, we had been getting it under control. This has completely pulled the rug out from underneath that progress.” – by Dave Levitan

For more information:

HIV-TB co-infection: Meeting the challenge. Report of the Forum for Collaborative HIV Research and TB/HIV Working Group of the STOP TB Partnership Symposium and Roundtable Discussions on HIV/TB. http://www.hivforum.org. Published Nov. 2, 2007. Accessed Nov. 21, 2007.