The advent of effective medications for treating HIV dramatically improved the outlook for both adults and children infected with HIV who had access to treatment, but the optimal timing for starting treatment remains controversial, particularly in children. A debate article in this week’s PLoS Medicine lays out the case for deferred treatment against the case for early initiation of treatment in children infected with HIV.

In laying out the case for deferred treatment, Dr Steven Welch (Consultant in Paediatric HIV and Infectious Diseases, Heartlands Hospital, Birmingham, UK) says that, “it remains rational to consider an individual child’s and family’s wishes and circumstances as well as the child’s risk of disease progression in deciding when to start treatment.” The hasty and injudicious use of antiretroviral medications in children, he argues, risks creating a cohort that has learned poor adherence habits, is infected with multi-drug-resistant viruses, and has been exposed to unnecessary cumulative drug toxicities.

Arguing the case for early initiation, Professor Di Gibb (Professor in Epidemiology and a Consultant Paediatrician at the Medical Research Council Clinical Trials Unit, London, UK), says that “deferring treatment initiation for as long as possible is no longer an option.” Professor Gibb lays out several reasons why she believes that early initiation is even more important in children than in adults—for example, children with HIV grow better if they receive antiretroviral medication.

Both authors point out that there has never been a clinical trial conducted on determining when to start antiretroviral medications in children, and they conclude by saying that the time has come to conduct such a trial.

Welch SB, Gibb D (2008) When should children with HIV infection be started on antiretroviral therapy. PLoS Med 5(3): e73.

Nearly half of all HIV-positive African adults who become infected with Salmonella die from what otherwise would be a seven-day bout of diarrhea. Now, UC Davis School of Medicine scientists have discovered how salmonella becomes lethal for AIDS patients. Their findings also implicate a mechanism by which HIV evades the powerful drugs used to treat AIDS.“We have found the defect in the immune response that allows Salmonella to cross the mucosal barrier of the gut, enter the bloodstream and infect other organs,” said Andreas Bäumler, a UC Davis professor of medical microbiology and immunology and co-author of the study.

The results of the study, which will be published online by Nature Medicine March 23, revealed that viral infection of the intestine results in the depletion of a type of white blood cell, called Th-17, in the gut mucosa. This T helper lymphocyte produces IL-17, a cytokine or chemical messenger that plays a crucial role in the inflammatory response, recruiting other immune system cells to the site of infection.

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Persons infected with a mutated HIV strain, transmitted from those who have the genetic advantages to control the virus, results in improved survival according to a recent study by South African researchers. The study, published March 21st in the open-access journal PLoS Pathogens, looked for genetic mutations in the infecting virus in 24 newly infected people in Durban, South Africa.

The study was conducted by CAPRISA (the Centre for the AIDS Program of Research in South Africa) researchers at the Universities of Cape Town, KwaZulu-Natal, Western-Cape and the National Institute of Communicable Diseases in South Africa. According to Professor Salim Abdool Karim, Director of CAPRISA, “It is significant that the mutations to HIV which occur in a person with advantageous genes leads to a low viral load, even when the virus infects a new person who does not have these ‘good’ genes. Low viral load is a goal of several HIV vaccines as it means that these HIV infected people will be clinically well for longer and be less likely to spread the virus.” … Continue Reading »

Researchers at the Scripps Research Institute have developed a new strategy for making an HIV vaccine. They found that upon HIV infection, the HIV virus binds to dendritic cells. Dendritic cells are immune system cells that act like guards in skin and organ linings. If a potential threat is detected, these cells travel to the lymphatic system to initiate an adaptive immune system response. Unfortunately, when these infected dendritic cells travel to the lymphatic system, they also unwittingly transport the HIV virus to its ultimate destination: the immune system’s T-cells.

Leveraging this discovery, the Scripps Research team’s experimental HIV defense works in two ways:

1. An artificial block called “glycodendrons” binds to the dendritic cells, preventing the HIV virus from binding.
2. The immune system creates antibodies to this artificial block which also recognizes HIV virus.

If the glycodendrons prove to stimulate a strong enough immune system response to preemptively stimulate the body to create antibodies, the Scripps researchers will have created the first successful HIV vaccine.

So far, the treatment has induced HIV antibodies in mice, and, in laboratory studies, has been able to block the virus from infecting immune cells.

Researchers at the University of Minnesota have recently solved the 3D structure of a protein that naturally protects people from the HIV virus. While scientists often know the chemical formula of most proteins, the 3D structure of a protein is often necessary to understand its function. This anti-HIV protein, APOBEC3G, is a “DNA binding protein” which seeks and mutates specific DNA sequences. Targets of APOBEC3G include many retroviruses, such as HIV, and retrotransposons, which are segments of DNA that can insert themselves randomly in a genome and induce mutations. Geneticists hypothesize that retrotransposons may be the remnants of ancient viruses or their evolutionary precursors. Transposons and remnants of transposons make up about 42% of the human genome.

Because an HIV viral protein, Vif, blocks APOBEC3G, HIV can replicate unchecked by the natural defense of the human immune system. Now that the structure APOBEC3G has been solved, hopefully new anti-HIV drugs may be developed which interrupt Vif from inhibiting APOBEC3G or modify APOBEC3G to resist Vif’s blocking mechanism.