Ask the Doc: HIV Vaccine Trials and the Anal Pap Smear

Q: I heard another HIV vaccine trial was stopped early this year. What happened?

A: The HIV Vaccine Trials Network "505 Study" was closed early by the data safety monitoring board or "DSMB" in April 2013 because the vaccine strategy did not work to prevent HIV infection nor did it lower the amount of virus in individuals who received vaccine and subsequently became infected with HIV. The job of the DSMB is to look at results of a study and to decide if the intervention being studied is safe and/or is generating data that would indicate that, in this case, the vaccine is working.

"Study 505" enrolled 2,504 volunteers at 21 sites in 19 U.S. cities and included men who have sex with men and transgendered women. The vaccine strategy studied included 2 types of vaccines and intensive follow up and counseling. At a scheduled DSMB review of the study it was noted that there were 41 new HIV infections in the vaccine arm and 30 in the placebo arm. Based on a statistical review of these data, the DSMB decided that the study should be stopped early because the vaccine strategy was not working and that they projected that ongoing follow up would be unlikely to demonstrate that the vaccine worked to prevent HIV infection.

Another hope was that the vaccine would help reduce viral load in individuals infected with HIV by controlling replication of the virus by a vaccine-generated immune response. This also did not pan out, further confirming the decision to close the study. So what does this mean for an HIV vaccine? The truth is; it means that it is time for researchers to go back to the drawing board. It is likely that the vaccines and strategy used in the 505 study will not be looked to again as an approach to prevent HIV infection. More analysis of the study will need to be done, and participants will continue in follow up.

Unlike the STEP trial that was stopped by its DSMB in 2007, this vaccine strategy was not associated with a statistically significant increased risk of HIV infection. Several other vaccines are being studied now and will be evaluated in future studies by the HIV Vaccine Trial Network and other similar research networks in the future. The story of HIV vaccine research is full of challenges, hopes, and some failures, but as science pushes forward, clinical and lab scientists continue to work toward a vaccine.

Q: My doctor offered me an anal pap smear. I have never heard of this before! What is it testing for?

A: Men who have sex with men, specifically those with HIV are at increased risk of anal cancer. Many epidemiologic studies have indicated that rates of anal cancer are higher in gay and bisexual men. In response to this many clinicians and some expert panels/guidelines have recommended that MSM be screened for anal cancer precursors using an anal pap smear, analogous to the cervical pap smear that many women will have as a part of their health evaluation.

The anal pap is done using a Dacron swab inserted into the anus to scrape off a small number of cells that can be looked at by a laboratory technologist to identify any cellular changes called "dysplasia." This "dysplasia" is often related to changes caused by infection with human papilloma virus (HPV). This family of viruses has some members that cause warts and some that are associated with anal and genital cancer. If an anal pap smear is positive the next step in evaluation is a "high-resolution anoscopy" where a clinician uses a small plastic tube to look at the anal tissue in detail and obtain biopsies to look for high grade lesions that may be on their way to becoming anal cancer. If these lesions are identified, they can be treated in the hope that cancer will be prevented.

Given the increased risk of anal cancer in our population, getting checked out using this test is probably worthwhile. The decision to do an anal pap smear needs to be weighed against the availability of doctors and other providers that can do the anoscopy. In related news, talk to your doctor about the HPV vaccine; they may recommend that you get vaccinated to prevent warts and some strains of HPV related to anal cancer.