Progress report: researchers make strides in global battle against HIV

Scientific advances may aid in stemming spread of disease

By Rebecca Bowers

This article originally appeared in the May 2007 issue of Contraceptive Technology Update. Consulting Editor Robert A. Hatcher, MD, MPH, Author Rebecca Bowers, Associate Publisher Coles McKagen, and Senior Managing Editor Joy Dickinson report no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.

Good news on the research front: Results from a major study indicate that treating genital herpes may help keep the AIDS virus under control in women with both infections and may reduce the spread of HIV as well.1 In the laboratory, scientists have successfully mapped a spot on the surface of HIV that may be vulnerable to an assault by antibodies, which could lead to development of an effective vaccine.2

Progress needs to continue at a rapid pace. In 2005, an estimated 4.1 million people worldwide were newly infected with HIV, mostly through heterosexual intercourse.3 At the end of 2003, an estimated 1,039,000 to 1,185,000 people in the United States were living with HIV/AIDS, with 24%-27% undiagnosed and unaware of their HIV infection.4

Why are scientists focusing on the virus that causes genital herpes (herpes simplex virus-2, HSV-2) in relation to HIV? HSV-2 infection almost doubles the risk of HIV acquisition; results from a meta-analysis indicate.5 Data from Rakai, Uganda, in HIV-discordant couples suggest that, on a per-contact basis, HSV-2 increases the risk of HIV acquisition fivefold.6

The problem is compounded when looking at the prevalence of the disease:

  • Approximately one out of five sexually active adults in the United States is HSV-2-seropositive.
  • In studies in Latin America and Peru, 60% of HIV-uninfected men who have sex with men are HSV-2-seropositive.
  • The rate rises even higher among HIV-infected women in parts of sub-Saharan Africa, South Africa, and Zimbabwe, where the HSV-2 prevalence is 70%.7

To conduct the trial among women coinfected with HIV and HSV-2, scientists from the Centre Muraz in Burkina Faso, the University of Montpellier (France), and the London (UK) School of Hygiene & Tropical Medicine enrolled 140 Burkina Faso women who were infected with the herpes and AIDS viruses. The women received valacyclovir or placebo pills for three months. Study findings indicate that having the herpes virus increased the replication of HIV and also revealed that the quantity of HIV in the blood and in the vagina was reduced by continuous anti-herpes treatment over three months.1

What is the next step?

These findings open new avenues for the prevention of HIV transmission and for the management of patients coinfected by the two viruses, says Philippe Mayaud, a scientist at the London School of Hygiene & Tropical Medicine and co-author of the current paper.

What are the next steps in HSV-HIV research? On the HIV transmission front, scientists will need to demonstrate that the effect seen on infectiousness or transmissibility of the virus actually translates into decreased transmission, says Mayaud. Several trials are ongoing, and results should be available within the next 18 months, he reports. Modeling studies will need to explore the population level impact of these therapies to assess their public health benefit, he notes.

When it comes to HIV disease progression, research should focus on the potential usefulness of using anti-HSV treatment during HIV disease, says Mayaud. For those infected with HSV-2, long-lasting therapies should be developed that do not depend on long-term intake of tablets, Mayaud believes. Safe and effective vaccines that would at least control the replication of HSV— if not prevent it altogether — would go a long way to prevent the transmission of HSV and HIV, he states.

"Such vaccines are currently not available," Mayaud says. "This should be an important priority area of research."

Progress on the HIV vaccine front has been challenged by the nature of the shape-shifting virus. Scientists led by a team at the National Institute of Allergy and Infectious Diseases (NIAID) now say they have been able to identify a key portion of an HIV surface protein as it looks when bound to an infection-fighting antibody.2 The protein component is stable and appears vulnerable to attack from a specific antibody, known as b12, that can broadly neutralize HIV, researchers report.2

The HIV virus mutates rapidly and continuously, which stymies attempts by the immune system to identify and destroy it. To further compound the problem, the virus is covered by sugary molecules, which prevent antibodies from slipping in and blocking the proteins the virus uses to latch onto a cell and infect it.

NIAID researchers have been able to decipher how the b12 antibody is able to bind to an unchanging surface on the tip of the HIV virus. They used an X-ray snapshot of the antibody as it locked into the target site on the virus, then used chemical blocks to provide a 3-D map of the target site.2 The resulting "map" may give researchers valuable clues in designing an effective vaccine. By understanding the structure of the virus, researchers may be able to improve on nature by designing an antibody that binds better than b12 and is easier for humans to produce.

Tongqing Zhou, PhD, a staff scientist in the NIAID's Vaccine Research Center's Structural Biology Section and lead author of the current research, says, "The detailed atomic level information from the HIV gp120:b12 structure tells us how a 'good' antibody works by attacking this weak link in the HIV armor, and it will guide us in the rational design of a future vaccine."

The next step in science is to use the information in designing and creating vaccines that will stimulate the immune system to generate large amounts of antibodies that would replicate or surpass b12's virus-killing power, says Zhou. However, the creation of such vaccines and the animal/human test processes may take a long time, and there will be many technical bumps ahead, he notes.

References:

  1. Nagot N, Ouédraogo A, Foulongne V. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med 2007; 356:790-799.
  2. Zhou T, Xu L, Dey B, et al. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 2007; 445:732-737.
  3. UNAIDS. 2006 Report on the Global AIDS Epidemic. Geneva; 2006.
  4. Glynn M, Rhodes P. Estimated HIV prevalence in the United States at the end of 2003. Presented at the National HIV Prevention Conference. Atlanta; June 2005. Abstract 595.
  5. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: A meta-analysis. J Infect Dis 2002; 185:45-52.
  6. Corey L, Wald A, Celum CL, et al. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: A review of two overlapping epidemics. J Acquir Immune Defic Syndr 2004; 35:435-445.
  7. Celum CL. Herpes simplex virus type 2 (HSV-2) & HIV: Interactions and Interventions. Presented at Herpes Simplex Virus Type 2 in HIV-Coinfected Patients: Prevention, Diagnosis, and Managements. Live web conference, June 16, 2005. Accessed at: www.medscape.com/viewarticle/507825.