The existing BCG vaccine that came into the market in 1921, has limited effectiveness in preventing people from TB. Further, the BCG vaccine that is used to prevent childhood TB may not be safe for children living with HIV.

That is why Aeras Global TB Vaccine Foundation and other agencies including Bill & Melinda Gates Foundation are pushing hard to accelerate research and development of safe and effective TB vaccines.

Currently there are seven vaccine candidate products in different stages of the research pipeline around the world.

One phase-III clinical trial in Tanzania which was sponsored by a US University, studied adults who were living with HIV, to see if there was any reduction in disseminated TB in that population. The promising results were announced in October 2008. "Aeras' vaccine advisory committee has looked at this vaccine as a first step. Aeras is providing our manufacturing expertise to see if it can be made at a larger scale," said Peg Willingham, senior director, eternal affairs, Aeras Global TB Vaccine Foundation.

"In our research pipeline at Aeras we have six vaccine candidate products," added Willingham.

One vaccine candidate is being developed if it can replace existing BCG vaccine with a better, modern and more effective BCG vaccine. This candidate is expected to start phase-I clinical trial later this year.

"The BCG or the improved BCG alone would be strengthened by having a booster shot — a different vaccine that will make the effect last longer and be more effective," explains Willingham.

So we have five boosters and one improved BCG vaccine candidate products in the research pipeline, adds Peg.

By end of 2010, there will be two different TB vaccine candidates being tested in 3 different phase IIb clinical trials. Phase IIb is a mid-way safety and effectiveness trial between phases II and III.

"We are going to test them in different populations. Our objective is to see if the vaccine will work on people of all ages, people living with HIV, and those who have latent tuberculosis," said Willingham.

"In the TB vaccine field globally, currently there are nine vaccine candidate products in different stages of clinical trials and many others in earlier stages of development. They all look very safe currently and we have seen some very early preliminary results that are promising but you cannot say that a Phase I result in a few people will guarantee similar results in large scale phase III clinical trial," explained Willingham.

"With sufficient resources, a new TB vaccine could be ready by 2020," said Willingham.

These clinical trials will be conducted at the highest international standards of ethics and quality because the product developers aim to get product approval by the United States Food and Drug Administration (US FDA) and such agencies in different countries around the world.

Meawhile, there is an urgent need to up collaborative TB-HIV activities. There is convincing evidence that scaling up collaborative TB-HIV activities, improves TB and HIV program performances.

"In 2008, there were an estimated 9.4 million incident TB cases globally, more than at any other time in history. Of these, there were an estimated 1.4 million who were co-infected with HIV," said Professor (Dr.) Anthony Harries, senior adviser to International Union Against Tuberculosis and Lung Disease (The Union) at the pre-conference session of the XVIII International AIDS Conference (IAC) in Vienna, Austria.

"In 2008, there were 1.8 million estimated deaths from TB, of whom 0.52 million were co-infected with HIV, giving an HIV-TB case fatality rate of 37 percent," said Prof Harries. "The number of HIV co-infected TB cases is too high, and the number of HIV-associated TB deaths is too high," said professor Harries.

Good news is that experts know what should be done to benefit public health — promote and effectively implement collaborative TB-HIV activities without delay!

"The collaborative activities that are needed to reduce the joint burden of the two diseases are based around a) decreasing the burden of TB in people infected with HIV, b) decreasing the burden of HIV in patients with TB, and c) establishing mechanisms for collaboration between the two programs," said professor Harries.

To improve the response, professor Harries explains it in three parts:

A — For people living with HIV

B — For people with TB

C — Establishing mechanisms for collaboration between TB and HIV programs.

A — For people living with HIV

"In people living with HIV (PLHIV) we must prevent TB through two strategies - 1) the three "Is" and 2) early start of antiretroviral treatment (ART).

The three I’s comprises: 1) Intensified case finding (ICF) 2) Infection control, and 3) Isoniazid preventive therapy (IPT).

"In simple terms this means that every time a person with HIV comes to a health facility, we must screen for TB. If we diagnose TB, we need to treat it rapidly thereby breaking transmission" said professor Harries.

"We must focus on maximizing natural ventilation in our clinics, especially those that serve people living with HIV, through big windows, high ceilings, and open skylights. If we are assured there is no TB in our patients, then we must consider giving isoniazid preventive therapy to reduce the risk of TB. The Achilles heel of the "Three I's" is the capacity to make a reliable diagnosis of TB in people living with HIV and with current technology this capacity is limited" said professor Harries.

"In all regions of the world, implementation of three I's is dismal. According to country reports, in 2008, only 9 percent of HIV-infected people who should have been actively screened for TB were screened, and only 3 percent of eligible HIV-infected people who should have been offered IPT were given isoniazid" said professor Harries.

The "three I's" is a good strategy, and in all regions of the world it needs scaling up. "Early start of ART in line with recent WHO recommendations (starting ART at CD4 cell counts of 350 cells/ uL or less) provides a welcome opportunity for getting more patients on to ART before tuberculosis develops and in this way reducing the risk of TB through immune reconstitution" said professor Harries.

Mathematical modeling has shown that universal HIV testing every year and immediate start of ART can significantly reduce HIV transmission and at the same time significantly lower the risk for TB. This is postulated to work in two ways: immune reconstitution in individuals thereby lowering the individual risk of TB; and by a reduction in viral load, less HIV transmission and less HIV in the community.

"Early start of ART must be promoted everywhere and the model for universal HIV testing and immediate start of ART needs to be assessed for efficacy and feasibility in the field and considered for scaling up," said professor Harries.

B — For people with TB

People who might be having TB, need to be diagnosed for HIV too, and ensure that a comprehensive AIDS care package is given. In high burden countries, there is a need to test all TB patients for HIV (through provider initiated HIV testing) and of those HIV-positive we must provide immediate cotrimoxazole preventive therapy and ART as soon as possible. "The most recent WHO advice issued in November 2009, is to give ART to all HIV infected TB patients regardless of CD4 count and to give it as soon as possible after the anti-TB treatment," said professor Harries.

"Fewer HIV-positive TB patients in the WHO-Euro region were started on cotrimoxazole (61 percent) compared with Africa (73 percent) but this may relate to different criteria for use. In all regions around the world, less than one-third of HIV-positive TB patients were started on ART. In 2008, 110,000 of 1.4 million co-infected TB patients received ART — this is less than 10 percent," he said.

"There is a need to promote HIV testing in all diagnosed TB patients, and to ensure that HIV-infected patients start ART. TB suspects without confirmed TB also need to be HIV tested and those who are HIV-infected need to be referred to structured HIV care and treatment" advised Prof Harries.

C — Establishing mechanisms for collaboration between TB and HIV programs

Mechanisms for collaboration between TB and HIV programs need to be strengthened. "In one area particularly, we need to listen to what HIV-infected TB patients want, and crucially co-locate TB and HIV care services within the same health facility. This will remove major logistical obstacles and costs for co-infected patients particularly on transport issues," remarked professor Harries.

"Our slogan should be — one patient, two diseases, one healthcare facility," said professor Harries.

The XVIII International AIDS Conference (IAC) has the apt theme of "Rights Here, Right Now" and we do believe that rights of people co-infected with TB and HIV will be protected — right to healthcare with dignity.