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Treatment and prevention needed to stave off transmission of HIV and STDs
Increased interventions are needed to improve prevention of HIV/AIDS and STDs worldwide.
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One of the academic organizations to which I belong is the American Epidemiological Society, an eclectic group of old boys and girls (literally) whose only function is to hold an annual meeting. It is an interesting mix of infectious disease and chronic disease epidemiologists, most of whom love to talk and critique the work of their colleagues. Several outstanding talks are the norm for these annual meetings, and this year’s meeting, held in March, was no exception.
The presentation that most captured my attention was entitled “Preventing Sexual Transmission of HIV and Other Sexually Transmitted Infections: Science, Morals, Ethics, Culture and Politics.” There is only one person in the world who could present that talk, of course, and that is King Holmes, MD, PhD, of the Center for AIDS and STDs, departments of global health and medicine, University of Washington.
Global issues
I’m going to devote this space to a brief summary of Holmes’ presentation, for he made a number of key points in understanding the global issues involved.
The first point Holmes made was called “The ART Gap,” which simply demonstrated, on the basis of experience in five African countries, that treatment alone without preventive services is a losing battle. Interventions to prevent STD transmission may be applied at the level of individuals, groups or entire communities. The interventions studied have included behavioral interventions, treatments, vaccines, vaginal microbicides and male circumcision. After a thorough review of the STD/HIV prevention literature, the following summary points emerged.
Behavioral-based interventions: There were 14 behavioral-based, randomized, controlled trials with objective STD outcomes. Most showed significant self-reported behavioral change, but only five reported a significant effect on STD rates. Of five randomized, controlled trials conducted in adolescents, only one reduced STDs. The effects in these studies were modest at best, and sustainability proved to be a common problem.
Abstinence-only programs for HIV prevention: The Cochrane Collaborative Review Group noted in July 2004 that “programs promoting abstinence were found to be ineffective at increasing abstinent behavior and were possibly harmful; more rigorous research is needed to determine the effectiveness of abstinence programs on HIV risk.” As of March 2007, no such rigorous research had been reported; no trial has measured HIV incidence or objective measures of STD diagnosis. Thus, when the moral or political debate is stripped away, there is simply no evidence to support effectiveness of abstinence-only programs.
Condom use: Where previously there was only limited evidence of efficacy, today there is abundant evidence of efficacy not only for HIV prevention, but also for a number of other STDs. To summarize the evidence, condoms are 80% to 95% effective in preventing HIV transmission, at least 50% effective in preventing Chlamydia trachomatis and gonococcal infection, and 30% to 70% effective in preventing herpes simplex virus-2 transmission. Condom effectiveness in preventing transmission of trichomonal infection and bacterial vaginosis is modest but still significant. They are about 25% effective in preventing syphilis, but strikingly more effective (70%) in preventing HPV transmission among women and men who have sex with men. These data are all the more striking when one recalls the intrinsic bias toward a null effect because of recall difficulty, selective condom use, incorrect use and breakage.
STD immunizations: There has been significant progress in this approach to prevention, save, of course, for HIV prevention. Hepatitis B vaccine was the first vaccine to prevent an STD, as well as the first cancer vaccine. In the 25 years since hepatitis vaccine was introduced, there has been steady improvement in vaccine penetration in the target populations, yet there is still room for improvement in target populations such as MSM. Only 32% of 3,000 MSM in one study seven years ago reported receiving one or more doses of hepatitis B vaccine, and only 17% had measurable anti-hepatitis B surface antigen alone.
HPV vaccine and the debates surrounding its use have been well-covered in both professional and lay media during the past year and need not be reiterated. Suffice it to say that, stripped of all the moral and political issues that surround its use, it is a superb vaccine that is highly effective in preventing HPV transmission. In Holmes’ words, “HPV vaccine is a slam dunk!”
HIV vaccines, of course, are another matter. Neither of the two VAXGEN rgp 120 trials showed efficacy in preventing HIV-1 infection or in ameliorating HIV-1 disease progression. There are presently two additional HIV-1 preventive vaccines in advanced clinical trials.
Topical vaginal microbicides: There had been a lot of optimism about this preventive modality because it could have a potentially huge impact in the African subcontinent. The N-9 gels appear only to make matters worse. Two recent trials of cellulose phosphate gels have been stopped because of either deleterious effect or no effect. The optimism has at least temporarily given way to disillusionment, but phase-3 trials with several other topical microbicides are underway.
Preventive treatment: Treatment of sex partners to prevent infection or re-infection of the susceptible partner has shown effectiveness in studies of trichomoniasis, HSV-2 and gonorrhea. However, the impact of antiretroviral drugs and/or HSV suppression on the risk for transmission to a susceptible partner is not clear. At the community level, there have been two trials in Africa to reduce HIV transmission; only one of them showed evidence of reduced HIV transmission rates, and long-term follow-up has been lacking. This is an area still under active study.
Male circumcision: By this time, there have been three large, randomized, controlled trials of male circumcision in Africa; at least two of them were stopped prematurely because of clear evidence of efficacy. The success of this mode of HIV infection prevention raises a number of challenges and opportunities. Male circumcision could have a huge effect on the AIDS epidemic, especially if it is protective in women as well as men, with a duration of more than 10 years. Scale up could be a big issue, as there would be a critical need for specialized surgical services. Behavioral disinhibition could potentially offset some of the benefits, so integration with other preventive programs would be desirable.
Thus, of the several rigorously designed and evaluated randomized, controlled trials of STD prevention, perhaps about half worked. Male circumcision has emerged as a promising preventive measure. Since the hepatitis B vaccine trials in the late 1970s, no preventive intervention has reduced the HIV/STD risk among MSM. Few of the preventive interventions that are actually effective have been widely implemented.
Holmes concluded his presentation by pointing out that, in addition to highly active antiretroviral therapy, to have a significant effect on the global HIV epidemic, we greatly need highly active retrovirus prevention.
Finally, I would like to express my gratitude to King Holmes for so generously sharing his slides with me.