NEW HIV VACCINE CANDIDATE RAISES INFECTION RISK

AGAIN, there appears to be no light at the end of the tunnel in the search for effective vaccine for Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) as evidence is mounting that an experimental vaccine to protect people against virus increases the risk of infection. The results of the study were made public at the AIDS Vaccine 2013 conference in Barcelona, Spain recently. Also, Russian scientists believes they have identified a new and more virulent strain of HIV. The subtype, known as 02_AG/A, is spreading rapidly and is now thought to account for more than 50 per cent of new HIV infections in Siberia.

The virus was first seen in the city of Novosibirsk in 2006 and is thought to be the most virulent subtype of the virus in Russia. The Moscow News reported that the new strain was discovered by scientists at the State Research Center of Virology and Biotechnology VECTOR in Siberia. Natalya Gashnikova, head of the retroviruses department at Vektor, said 02_AG/A could spread through the population much more quickly than the current main HIV strain found in Russia.

The number of HIV positive people in Novosibirsk has jumped from 2,000 in 2007 to 15,000 in 2012, according to Russia’s Federal AIDS Centre and 50 per cent of the new cases have been caused by 02_AG/A. The newly identified subtype is not confined to Siberia – cases have also been reported in Chechnya, in the south of Russia, and Kyrgyzstan and Kazakhstan. Also, some 100 000 more people living with HIV/AIDS in Brazil are set to receive life-saving antiretroviral therapy (ART) under a major new initiative that will offer early treatment to all HIV-positive adults.

It is estimated that between 430 000 and 520 000 people are living with HIV in Brazil - just over 300 000 of which are currently accessing treatment. The initiative will not only enable more people living with HIV to stay alive and well, it is also part of the government’s efforts to harness the preventative impact of antiretroviral therapy to stop new HIV infections. Antiretroviral therapy is a powerful HIV prevention option as studies have shown that it can reduce the risk of transmitting the virus to a sexual partner by up to 96 per cent.

This is not the first report of problems with the vaccine made by pharmaceutical giant Merck, based in White-house Station, New Jersey. In 2007, researchers prematurely cancelled two clinical trials after the vaccine- comprising a vector made from the common-cold virus adenovirus 5 (Ad5) modified to contain HIV genes - proved ineffective at preventing HIV.

In the larger of the two trials, called STEP, the vaccine seemed to increase the risk of infection, especially in men. But the risk declined over time and narrowed further when the researchers accounted for factors such as circumcision, sexual activity and previous infection with Ad5.

The second trial, in Phambili, South Africa, was shut down after little more than six months, and its 800 participants were told whether they had received the vaccine or a placebo. When a team led by Glenda Gray, a paediatrician at the University of the Witwatersrand in Johannesburg, South Africa, followed up earlier this year, it found that 119 of those patients had contracted HIV. Overall, people who had received the vaccine were significantly more likely to be infected than those who had received the placebo.

We are resuming a leading role in the response to the AIDS epidemic in the world. Currently, only two countries - the United States and France - recommend the use of early treatment. The Clinical Protocol document also sets out ways in which to clearly define and simplify treatment regimens, while strengthening adherence and the long-term effectiveness of antiretrovirals. There are plans to introduce a combined fixed dose, a 3-in-1 medication, as the preferred first-line regimen. This treatment is scheduled to be available in 2014.

 "Brazil is once again showing bold leadership in the response to AIDS - and is doing so in an open and inclusive manner, through public consultation," said UNAIDS Country Coordinator Georgiana Braga-Orillard. “The initiative will improve the lives of people living with HIV and reduce deaths due to AIDS across the country.” The report is now under public consultation until November 5 and will be finalized before the end of the year.

Gray said: “I spent most of this year trying to find a non-biological reason for these results. But when her team accounted for biological and lifestyle differences in their participants, it found that the vaccine recipients were still significantly more likely to have HIV. In a separate study, biostatistician Peter Gilbert of the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, Washington, analysed the STEP and Phambili trials together and found that the vaccine seems to raise the risk of infection by 41 per cent.

Gray said the findings are confusing, as the previous explanation for the increase in infection rate observed in the STEP trial had been that the vaccine briefly overstimulated recipients’ immune systems, making them more susceptible to HIV.

Some researchers question the results. Dan Barouch, a virologist at the Beth Israel Deaconess Medical Center in Boston, Massachusetts, is sceptical that the difference in infection risk was as great as Gray’s results indicate. He says the findings are difficult to interpret because most of the patients contracted HIV after they knew whether they had received the vaccine. People who received a vaccine might have been more likely to engage in risky sexual behavior. Hildegund Ertl, a vaccinologist at the Wistar Institute in Philadelphia, praised the statistical analysis used by the studies but says it is not clear why the vaccine increases risk.

It is an important question to answer: in April, the US National Institutes of Health in Bethesda, Maryland, shut down a third clinical trial of a different Ad5-based vaccine called HVTN 5051. There is no evidence that this vaccine increased the rate of HIV infection, but researchers plan to follow trial participants closely for the next few years, says Larry Corey, an FHCRC virologist who heads the group that conducted that trial as well as the STEP and Phambili tests.

Clinical trials of new HIV vaccines that use different adenoviruses are now beginning, and Gray says they should proceed with caution. Her group is beginning a clinical trial in South Africa that builds on one conducted in Thailand. The US Military HIV Research Program, based in Bethesda, Maryland, has found that a vaccine containing HIV fragments in a poxvirus reduced the risk of infection by 31 per cent in HIV infections in a general Thai population. Gray and her colleagues are also continuing to investigate what went wrong in the Ad5 trials so as to avoid similar failures in the future.

HIV can be divided into two main types - HIV-1 and HIV-2. HIV-1 is the more virulent of the two and is, therefore, responsible for the majority of cases. HIV-1 can also be divided into subgroups and the newly discovered 02_AG/A is a subgroup of HIV-1. All of the subgroups are transmitted from person to person through the same transmission methods - including unprotected sex and sharing needles - but some are easier to pass on than others. 02_AG/A is thought to be easier to transmit than some other subtypes.

United Nations (UN) figures show that the only regions where the number of HIV infections is increasing are Eastern Europe and Central Asia – 52 per cent of people with HIV in this area live in Russia. This is believed to be partly because there is little awareness of HIV in many parts of Russia and because Russian school offer very little sex education. The number of new HIV infections globally has plummeted by a third since 2001 and more than halved among children, the United Nations recently revealed.

Globally, 2.3 million people contracted the AIDS virus last year - down 33 per cent from 2001, while 260,000 children became infected - 52 per cent less than in 2001. Executive Director of Joint United Nations Programme on AIDS (UNAIDS), Michel Sidibe, said: “The annual number of new HIV infections continues to decline with especially sharp reductions in the number of children newly infected with HIV.”

Last year, 1.6 million people died of AIDS-related deaths, down from 1.8 million in 2011 and 2.3 million in 2005. The report showed that 9.7 million people in low and middle-income countries, the bulk of those infected, had access to HIV drugs last year, compared to only 1.3 million seven years earlier. While the hike is impressive, it falls short of a UN target announced two years ago to reach 15 million people by 2015.

Some 35.3 million people were living with the virus last year - about 70 per cent of them in sub-Saharan Africa - up from 30 million in 2001.