News Tips from the 2005, 12th Conference on Retroviruses and Opportunistic Infections

NEWS TIPS FROM THE 2005, 12th CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS (CROI), FEB. 22 - FEB. 25, BOSTON, MASS.Listed below are several key presentations surrounding the 12th CROI from researchers affiliated with Johns Hopkins.

STUDY DOCUMENTS INITIAL DIFFERENCES IN SEXUAL TRANSMISSION OF HIV BETWEEN MALES AND FEMALES(Embargoed for release at 1:30 p.m. ET, Thursday, Feb. 24; Poster presentation #339, Hall D, Hynes Convention Center.)

A genetic analysis of viral RNA from 10 heterosexual couples, in which one partner has sexually transmitted HIV to the other, provides the first documentation of some differences in how the virus infects males and females. According to the Hopkins researchers who led the study, this initial research is essential to understanding why these differences occur and for future development of a vaccine or other preventive methods that could stop sexual transmission of HIV-1.

The couples in the study come from the Rakai Cohort, a Uganda-based population in a long-term study of HIV infection. The researchers tested each couple's viral RNA to determine which variants, or kinds of HIV-1 strain, were present in each man and woman. Variants of HIV-1 can be distinguished by differences in the gene (gp160) for their protein envelope. The findings showed that only a subset of HIV-1 variants in the initially infected partner was transmitted to the newly infected partner, and the predominant variant in males was not the kind that infected their female partners. And, women infected by men had a greater number of variants than men infected by women.

The selection of HIV-1 during sexual transmission: differences in gp160 diversity in male-to-female versus female-to-male transmission. Oliver Laeyendecker, Jordyn Gamiel, James Shepard, Xianbin Li, David Serwadda, Nelson Sewankambo, Fred Wabwire-Mangen, Francine McCutchan, Jonathan Toma, Wei Huang, Ronald Gray, Maria Wawer, and Thomas Quinn

DUAL TESTING BETTER FOR MONITORING NEW CASES OF HIV(Embargoed for release at 5:30 p.m. ET, Friday, Feb. 25; Oral presentation, Abstract #172, Ballroom A, Hynes Convention Center.)

Johns Hopkins researchers will present results showing that tighter, dual testing standards work better for accurately distinguishing between new and old cases of HIV. Current testing standards are based on a single test called the serological testing algorithm for recent HIV seroconversion, or STARHS for short. STARHS relies on differentiating newly infected from chronically infected individuals based on the quantity, or levels, of antibodies to HIV present in patients' blood. Normally, the antibody concentration to HIV increases over time during the first six months of infection. However, effective use of anti-retroviral therapy can depress viral counts in patients to undetectably low levels, which also lower the antibody-to-HIV concentration in the blood. This creates confusion for those responsible for monitoring new infections and spread of HIV. According to the researchers, large numbers of artificially "new" cases also have the potential to hamper measurements of how successful are global treatment efforts in Africa, where aid from the United States is set to make antiretroviral therapy more widely available.

The Hopkins team successfully determined new cases from old by adding the Affinity/Avidity test to the current STARHS protocol, the test widely used by the United States Centers for Disease Control and Prevention. This second test measures the strength of antibody-antigen binding in the immune system's response to HIV infection. An immature response from a new infection produces weak binding, whereas a mature infection involves strong binding. In a cross-sectional study of more than 1,500 patients showing up in the Hopkins Emergency Department from June to August 2001, the testing of blood samples by STARHS showed 11 cases of new infection, but dual testing with Affinity/Avidity showed only six. Information gathered from interviews with two of the five discrepant patients confirmed that these two were taking antiretroviral therapy, masking their old infection as new.

The effect of ART on cross-sectional incidence testing: the 2001 Johns Hopkins Hospital sero-survey as an example. Oliver Laeyendecker, Charlamine Henson, Bobbi Jo Hone, Richard Rothman, KerrunneKetlogetwe, Judy Shahan, Gabor Kelen, and Thomas Quinn

ARCHIVAL VIRUS STILL NECESSITATES LIFE-LONG ANTIRETROVIRAL THERAPY(Embargoed for release at 4 p.m. ET, Friday, Feb. 25; Symposium on key topics in anti-retroviral therapy, Main Auditorium, Hynes Convention Center.)

Johns Hopkins researcher and infectious disease specialist Robert Siliciano, M.D., Ph.D., will provide an update on the scientific rationale behind the use of antiretroviral therapy, focusing on the mechanisms that allow life-long persistence of HIV even in patients on potent medication. Siliciano, a professor of medicine at Hopkins and a Howard Hughes Medical Institute investigator, has recently found a second reservoir for HIV in the body, where it "rests" and is not affected by current therapies that prevent the virus from replicating.

While the Hopkins findings await publication, Siliciano says the additional viral population makes it unlikely that HIV can be eradicated from the body, even though current therapies effectively reduce the replicating virus to levels undetectable by standard clinical techniques. According to the Hopkins team, the so-called second reservoir of HIV harbors unique HIV variants, or kinds of the virus that have generated in a patient, distinct from those that persist in a previously discovered reservoir in resting, CD4-positive T-cells.

The reservoir for HIV in resting CD4 cells harbors all of the major variants and all have the potential to reemerge from this reservoir at later times. However, recently published data by the Hopkins team on blips in HIV levels concludes that this archival virus is not mutating to become drug-resistant.

Scientific rationale for antiretroviral therapy in 2005. Robert Siliciano