/ 23 July 2009

Vaccine trials offer hope in fight against drug-resistant TB

Scientists attending the Fifth International Aids Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town highlighted the high mortality rates stemming from HIV and tuberculosis (TB) co-infection and warned of a potentially devastating drug-resistant TB epidemic.

However, they offered a glimmer of hope with new evidence of the effects of antiretroviral therapy (ART) on patient survival rates and six new vaccines currently in the pipeline.

Tuberculosis is considered a major driver of mortality for people living with HIV.

According to Gerald Friedland of Yale University, ‘HIV/Aids underlies the explosive growth of TB, and TB is the major cause of morbidity and mortality in people living with HIV.”

About 1,4-million of the 9,27-million people infected with TB worldwide are also infected with HIV, and 80% of the world’s co-infected live within sub-Saharan Africa, with 29% in South Africa alone.

Despite these grim figures, Friedland pointed to findings that demonstrate severely decreased mortality in co-infected people with the use of ART.

A study published in the Journal of Aids showed that with an increase in CD4 count, a measure of immune response, resulting from ART, TB treatment resulted in a 90% success rate.

Another study of Johannesburg miners showed that 30% of those with CD4 counts below 50 were co-infected, while only 5% of a those with a CD4 count above 350 were co-infected.

Friedland claimed ART use is essential to saving the lives of those co-infected. ‘Very important to survival is the administration of antiretroviral therapy, perhaps even more so than [TB drugs],” he said.

Studies on ART’s impact on TB comes amid several other findings presented at this week’s conference showing that early ART initiation greatly diminished mother-to-child transmission rates, and even assists in malarial survival for HIV-positive patients.

A call for early uptake of ART for all those living with the virus was also claimed to offer the key to worldwide eradication of the epidemic.

While promising studies were presented on controlling HIV and TB co-infection, the increasing worldwide occurrence of multi-drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) have spurned doctor’s fears of a global, largely untreatable epidemic.

Drug-resistant TB was first diagnosed in Tugela Ferry KwaZulu-Natal in 2005. Cases have since been found worldwide, but the disease remains most concentrated within sub-Saharan Africa.

Because drug-resistant tuberculosis is still relatively new, ‘the true burden of [the disease] is not known,” explained Friedland, who nevertheless considers it a ‘global threat”.

Friedland pointed to the high mortality rates among the first Tugela Ferry cases, with 98% of those dying just weeks after diagnosis, to demonstrate the potential impact of the disease.

‘We saw rapid mortality rates, [with] the median time of survival from when the culture was taken [just] 16 days,” he said.

Since the first diagnosis, ‘the epidemic has continued in Tugela Ferry,” Friedland said, with 250 cumulative cases between 2005 and 2007.

Mathematical modelling predicts 12 000 to 14 000 new cases of drug-resistant TB in Tugela Ferry alone within the coming years. The majority of those affected at the site also have HIV.

But ART may again offer an answer to the high rate of mortality in those co-infected. Friedland and colleagues used ART as part of a TB/HIV integration study at Tugela Ferry, finding that the mortality rate dropped from 40% to 12%.

In addition to the use of ART, scientists are currently working on the development of several vaccines to replace the current TB vaccine, BCG. These new vaccines could be used in both HIV-positive and HIV-negative persons.

According to Jerald Sadoff of the Aeras Global TB Vaccine Foundation, BCG, made between 1906 and 1921, is ‘the world’s most widely used vaccine, and probably the least effective — it neither works, nor is safe.”

The World Health Organisation recommends that HIV-positive infants not be vaccinated because of the high rate of complications.

A safer vaccine is ‘desperately needed”, Sadoff said. ‘We’re going to have a very hard time treating our way out of this epidemic — Modelling studies show that we won’t beat the pandemic without a vaccine.”

According to Sadoff, a new vaccine would save 14-million lives by the year 2050.

Vaccine trials are currently under way in Cape Town, with others still in the lab.

Referring to the six vaccine candidates, Sadoff said: ‘This is the most promising pipeline of new TB vaccines that we’ve ever had,” predicting that ‘we’ll have a new vaccine regimen for TB in the 2014 to 2016 time frame.”