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Evolving HIV Strains Worry Indian Scientists

NEW DELHI, Nov 29 2012 (IPS) - While India has drastically reduced the spread of HIV over the past decade, new strains of the virus that cause acquired immunodeficiency syndrome (AIDS) are troubling medical scientists in this country.

The Joint United Nations Programme on HIV and AIDS, or UNAIDS, in its 2012 report, praises India for doing “particularly well” in halving the number of newly affected adults between 2000 and 2009.

But India – home to 2.4 million people living with HIV, one million of whom are on anti-retroviral (ARV) therapy – will need to pay attention to the proven fact that the Human Immunodeficiency Virus Type I (HIV-1), the most common and pathogenic strain of the virus, has been undergoing a process of fairly rapid viral evolution.

Of the various genetic families, HIV-1 subtype C is responsible for nearly 99 percent of infections in India and has a significant presence in China, South Africa and Brazil as well.

Now, scientists working at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) in Bangalore have found a family of five new strains of HIV-1 subtype C, two of which appear to be outstripping the standard viral strain.

The study is the first of its kind to identify that a major family of HIV-1 is undergoing evolutionary modification,” Prof. Ranga Udaya Kumar of the molecular biology and genetics unit at JNCASR told IPS.

Kumar said that although the studies at the Centre do not show the new strains to be “more pathogenic”, there are reasons to believe that they are “more infectious”.

The results of the JNCASR study were first published by the American Society for Biochemistry and Molecular Biology in the Nov. 6 edition of the peer-reviewed Journal of Biological Chemistry.

“The new viral strains appear to contain a stronger viral promoter,” said Mahesh Bachu, who led the team of researchers at JNCASR. A promoter is a region of DNA that codes for whichever protein the cell is trying to produce. In other words, a virus with a stronger promoter is expected to produce more ‘daughter viruses’ and spread faster in a host population.

“Importantly, in the laboratory experiments the new HIV strains were found to be making more daughter viruses compared to the standard viral strains,” Bachu said.

Retroviruses that cause AIDS reproduce by transcribing their ribonucleic acid (RNA) into DNA using an enzyme called reverse transcriptase. The resultant DNA inserts itself into a host cell’s DNA and is reproduced along with the cell and its daughters.

“In addition to making more daughter viruses, people infected with the new HIV strains seem to contain more virus in their blood,” Bachu told IPS, adding that data for the study was generated from 165 samples gleaned from hospitals in diverse parts of the country.

Collaborators in the study included the YRG Centre for AIDS Research and Education (YRG CARE) in Chennai; St John’s National Academy of Health Sciences, Bangalore; the National Institute of Mental Health and Neurological Sciences, Bangalore; and the All-India Institute of Medical Sciences (AIIMS) in New Delhi.

The clinical findings have been substantiated by laboratory experiments using viral, immune and molecular strategies, Bachu said. “A similar process of viral evolution has also been observed in South Africa, China and southern Brazil – countries that have the same family of HIV-1.”

Significantly, when Bachu and his team first observed the new strains, during earlier studies conducted from 2000 to 2003, their prevalence was quite low – approximately one to two percent of each of the five variants.

A decade later, the prevalence of three of the five new HIV-1 groups had multiplied, with one group increasing from two percent during the 2000-2003 period to 20-30 percent in 2010-2011.

According to Bachu, it is important that subjects infected with the newer 4-kappaB strains show more plasma virus in their blood than those infected with the existing 3-kappaB HIV strain.

“It is possible that a higher viral load permits an enhanced transmission advantage to 4-kappaB strains of HIV, contributing to successful spread of the new viruses,” Bachu said.

“The findings raise several questions with serious implications for viral fitness, evolution and disease management,” according to Kumar. “The most important of these concerns is the possibility of the new HIV strains altering the landscape of HIV demographics in India.”

Both Kumar and Bachu caution, however, that the JNCASR “data should be considered only as suggestive and not conclusive”.

JNCASR and its collaborators are now conducting observational clinical studies to determine if the new HIV strains are more infectious than the existing one.

“It is for clinical scientists to see if the new strains of HIV are likely to cause rapid disease progression to AIDS,” Dr. Nagalingeswaran Kumarasamy, chief medical officer at YRG Care, told IPS.

Kumarsamy said that, as things currently stand, there is no cause for alarm. “We need to further study the new strains and see, for example, if there is a need to start ARV therapy earlier than usual.”

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