HIV infection: progress on several fronts at once

The Conference on Retroviruses and Opportunistic Infections was held in Seattle (USA) - the largest forum dedicated, among other things, to HIV, and the fight against it was the focus of the event.

The pathos of the meeting defined progress made on several fronts after the virus had baffled scientists with its unknowability for nearly three decades. A host of new techniques have been proposed, from flushing latent HIV out of cells to extracting immune cells from the body, altering them so that they become resistant to the virus, and implanting them back.

The stumbling block remains the fact that HIV “lies” in “reservoirs” of latent infection, and even strong drugs cannot reach it. “We first need to bring the virus out of latent state, and only then will we help the immune system deal with it,” said Kevin De Cock, director of the Center for Global Health at the U.S. Centers for Disease Control and Prevention.

HIV, which emerged more than 30 years ago, has already infected more than 33 million people. Thanks to preventive measures, early detection, and new antiretroviral drugs, AIDS is no longer a death sentence. However, cost, side effects, drug resistance, etc., make lifelong use of antiviral drugs less than ideal. That’s why the International AIDS Society officially declared its mission last year to find a panacea.

The first human trials of vaccines designed to prevent and treat the infection ended in disappointment. The HIV “provirus,” embedded in the host cell’s DNA, remained inaccessible. Unfortunately, one such provirus is sometimes enough for the infection to subsequently spread throughout the body. The matter is complicated by the fact that HIV has “reverse transcriptase,” meaning it constantly mutates, and the immune system simply cannot keep up with it. The vaccine induces the formation of antibodies that recognize and bind to very limited types of the virus’s surface.

"Developing a vaccine has been incredibly difficult," said John Coffin of Tufts University in the US. "But in recent years the pendulum has swung back." He is referring to recent advances in molecular technologies that are allowing researchers to gain deeper insight into the mechanism of HIV infection.

For example, Dennis Burton of the Scripps Research Institute (USA) reported on the results of a study showing that "broadly neutralizing antibodies" are capable of recognizing HIV and penetrating it (work in this direction has been going on for years). And Merck & Co. presented data showing that its cancer drug Zolinza, also known as vorinostat, can cope with latent HIV infection. The main thing here is that the virus can be reached. And which molecules should be used is another question.

At the same time, Philip Gregory of Sangamo BioSciences is developing a gene therapy: white blood cells with the CD4 glycoprotein are removed from the body, the CCR5 gene that allows them to become infected with HIV is switched off, and then returned. The cells remain that way forever and produce offspring with the same characteristics.

The first trial of this method has yielded mixed results: out of six patients, only one was cured, and that one had a natural genetic mutation. Future tests will begin with HIV-infected people undergoing a course that reduces the number of lymphocytes in the bone marrow so that CD4 GM cells can take up more space there.

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