Notes Washed Up in a Bottle

Don. W. MacCorquodale M.D. M.S.P.H.

Periodic Notes From the Field on Philosophy and Science.

HIV/AIDS PREVENTION

          Nearly a dozen potential preventive approaches generally characterized by simplicity, such as the female diaphragm and improving genital hygiene are currently under study (Cohen J.   Prevention cocktails:   Combining tools to stop HIV/S spread.   Science 2005; 309:   1002-1005).

Several weeks ago a study from South Africa was reported that showed that male circumcision reduced the risk of acquiring AIDS by 65%.   Each of the interventions could do more harm than good by leading people to take more sexual risks.  

          A study conducted recently looked at 8,000 men and women in four locales, two of which had much higher HIV prevalence than the others.   Circumcision and pre-existing infection with the genital herpes virus “seemed to account for much of the difference in prevalence.”   A second study of 15,000 adults in the Rakai District of Uganda studied “discordant” couples in which only the woman was infected with HIV.   If the male partner was circumcised, which occurred in 50 instances, the woman never transmitted the HIV virus to him.   Nearly 17% of the uncircumcised men had acquired the virus.  

          A specialist at the London School of Tropical Medicine and Hygiene has estimated that if the proportion of circumcised men increased from 10% to 100% in Ndola , Zambia , the prevalence of HIV in adults would drop from 27% to 7%.   The estimate assumes that circumcision affords but 50% protection.

          There are two ongoing trials using daily acyclovir to see whether suppressing the HSV-2 virus can reduce the transmission of HIV.   One trial includes 3,000 people who are not infected with the virus.   The other is recruiting 600 couples who are discordant for the HIV virus.   Acyclovir is the ideal drug for such studies since it is virtually nontoxic, and there is little danger that daily doses will result in drug resistant strains of the virus.

          If acyclovir treatment of HSV-2 is effective as an HIV prevention strategy, it would greatly affect the AIDS epidemic.   HSV-2 infects from 22% of adults in the United States “to a staggering 70% of women in southern Africa ” among HIV uninfected people.   More that 80% of HIV-infected adults are co-infected with the HSV-2 virus.  

          A graduate student at the London School of Hygiene used the four-city data to show that 15 years after HIV was introduced into those locales, HSV-2 accounted for over a third of the new infections with HIV.  

          Antiretroviral agents reduce viral loads, which suggest that anti-HIV medications might be useful for prevention as well as treatment.   This has not been proven.   Myron Cohen of the University of North Carolina is conducting a trial which hopes to enroll 1,750 discordant couples to test the approach.  

          Several monkey studies have shown that a drug called tenofovir works very well in pre-exposure prophylaxis, PreEP.   Researchers gave animals the drug and then tried to infect them with SIV, the simian virus similar to HIV.   Monkeys that had received the drug up to 2 days before the SIV “challenge” were not infected; however, a recent study at CDC showed that tenofovir treated monkeys became infected after repeated challenges.   Many researchers hope that PrEP will work to some degree in humans, and seven clinical trials are now evaluating the “safety and efficacy” of PreP.

          Cohen said recently that “the idea of doing circumcision on a mass scale is kind of daunting.   Providing pills is a bit simpler.”  

          Investigators are beginning to incorporate tenofovir and other antivirals into microbicides, gels or cream that are put into the vagina – or in one new study, the rectum.   Five efficacy trials are now underway with nonspecific formulations such as buffering agents and detergents.   These compounds must be used about an hour before intercourse.   In contrast, tenofovir and some other antivirals remain active longer and may only need to be used once a day.  

          Early detection of HIV infection offers an opportunity to prevent transmission of the virus when the risk is highest.   Typically, risk of transmission is highest before people even know they are infected.  

          Researchers at the University of North Carolina have used polymerase chain reaction, PCR, to detect HIV in blood pooled from thousands of people visiting STD clinics.   If the virus is detected, the researchers break the pool into smaller and smaller pools and eventually identify the individual patients infected with the virus.   This technique, which cost less than $4 per blood donor, identified 23 acutely infected people in North Carolina .  

          Nancy Padian at the University of California , San Francisco , is studying the possibility that using a diaphragm may prevent male-to-female transmission of HIV.   The diaphragm should prevent HIV from reaching the cervix and endocervix where most female infections occur.  

          King Holmes of the University of Washington , Seattle , is studying the possible role of basic hygiene of the penis in preventing HIV infection.   He is investigating whether wiping the penis with an ethanol-based gel can prevent the transmission of HIV, HSV-2, and other sexual transmitted organisms.  

          The author closed this review by observing “. . . if more of these unflashy biomedical alternatives prove their worth, they could powerfully slow HIV, which now affects another 14,000 people – half of them between 15 and 24 years old – each day.”  

          COMMENT:   I was fascinated by the ingenuity our research colleagues have shown by exploring so many approaches to HIV/AIDS prevention.   Unless acyclovir has come down in price appreciably, I don't think its use in developing countries will be feasible.   The drug is far too expensive.   Similarly, I rather doubt that testing pooled blood to ultimately identify individuals recently infected with HIV will be possible.   Again, it will be very expensive.  

          I was surprised and not a little shocked to learn that the HIV/AIDS epidemic is spreading at such an enormous rate.   In the past epidemics have tended to reach a peak and then, to decline.   The daily increase in the number of new infections suggests to me that the HIV/AIDS has not reached a peak and is unlikely to do so in the near future.

H5N1 INFLUENZA

          Birds are the natural hosts of influenza A, but most avian viruses are not transmitted to humans.   The current influenza A/H5N1 virus is more virulent than previous similar viruses, and it is associated with human infections.   Since it appeared in Hong Kong in 1997, the H5N1 virus has spread to most countries in South East Asia and to Russia and Kazakhstan , which directly threatens Europe (Ekdahl K.   H5N1 influenza and the implications for Europe .   Editorial.   BMJ 2005; 331:   413-414).

          The editorialist pointed out that there are three prerequisites for a pandemic:   a new viral subtype for which humans are immunologically naïve must be transmitted to humans; it must replicate and cause disease; and it must be efficiently transmitted among humans.   The H5N1 avian virus lacks the third step, but human to human transmission could occur through further mutation of the genome, or through “reassortment,” i. e., mixing with a virus of human origin in a co-infected host.

          It is difficult to assess the risk of a pandemic.   The current situation in South East Asia with low grade transmission to (and between) humans, may remain stable.   Alternatively, there might be a pandemic with a virus of unknown pathogenicity.  

          Europe would be vulnerable to a pandemic, and if 25% or more of the population were affected, food and fuel supplies would be severely threatened, unless appropriate preparations were made, including prophylaxis for key staff and plans within organizations for maintaining activities with a reduced work force.  

          WHO has produced guidelines for public health interventions, including appropriate surveillance and detection, stockpiling of antiviral drugs, and timely vaccine development.   WHO has also suggested non-medical interventions such as early self-isolation of cases and canceling of mass events.  

          Finally, the author of the editorial observed:   “A pandemic will occur in the future.”   He added that European institutions are preparing for an influenza pandemic, with the result that Europe will be better equipped to tackle seasonal influenza and other major public health crises.

            COMMENT:   The editorialist announced early on that “it is difficult to assess the risk of a pandemic, but concludes his editorial by announcing that “a pandemic will occur in the future.”   Curious.