An expanding range of ways to outwit the virus

From diaphragms to vaccines, technologies old and new are being used against the HIV epidemic, in the hope that science will succeed where attempts to alter human behaviour have not done as well as anticipated. MALE CIRCUMCISION An old, if controversial, custom showing signs of effectiveness against the spread of HIV is male circumcision. The procedure is thought to work by removing the microclimate that exists under the foreskin, which can provide a comfortable environment for bacterial and fungal growth, and thus an enabling environment for HIV to enter the body. Slicing off a man's foreskin appears to reduce his chances of contracting HIV by up to 65 percent, according to a study carried out near Johannesburg, South Africa's economic hub. The difference was so noticeable that the clinical trial was stopped early, because it was considered unethical not to offer the uncircumcised men in the control group the chance of having the operation. More than 30 studies around the world have suggested that circumcision can offer some protection against HIV, but this is the first time a randomised, controlled study has been undertaken. Two similar trials are underway in Uganda and Kenya. The results are expected later this year, and if they support the Johannesburg study, male circumcision is likely to be added to the cocktail of prevention mechanisms. Botswana recently passed legislation to promote counselling about the procedure for all mothers of male infants. Research in Rakai, Uganda, is seeking to discover whether circumcising men already infected with HIV will reduce the risk of their uninfected partners catching the virus. Nevertheless, the World Health Organisation (WHO) and UNAIDS cautioned in a statement: "If male circumcision is confirmed to be an effective intervention to reduce risk of acquiring HIV, this will not mean that men will be prevented from becoming infected with HIV during sexual intercourse through circumcision alone. It will therefore be essential that it be part of a comprehensive prevention package, which includes correct and consistent condom use, behaviour change, and voluntary counselling and testing." USING DRUGS TO PREVENT HIV Sexually transmitted infections (STIs), and particularly the "genital" forms of herpes (herpes simplex virus-2), appear to strongly increase the chances of transmission of HIV. As a result, there is an interest in giving acyclovir, a relatively safe antiviral that works against herpes, as a prophylactic. International studies are looking at the impact of daily acyclovir on new infection rates among HIV-negative people, and also among sero-discordant couples where only one person is carrying the virus. Herpes is highly infectious - 70 percent of HIV-negative women in southern Africa are thought to have it, and this rises to over 80 percent among HIV-positive women. Using antiretrovirals to prevent, rather than treat, HIV infection is another prevention technique being developed. Although this approach had been discussed for years, fears of encouraging the development of drug-resistant HIV slowed research. The registration of tenofovir, a relatively safe drug with a long half-life (allowing for once a day dosing, which should improve adherence and consistency in drug levels) and a high resistance barrier (it is difficult for HIV to evolve to become drug resistant and remain viable) has led to a renewed surge of interest. Several clinical trials are underway in African countries. Another avenue to curbing the spread of HIV is to detect people who are very newly infected. People in the "acute" stage of HIV infection are hyperinfectious, carrying extremely high levels of HIV in their blood that would not otherwise be seen until the terminal stages of AIDS. It is extremely difficult to detect the virus during this acute stage, not least because the usual antibody tests may not register the new infection. Research in Malawi found that five percent of men attending clinics for treatment of STIs, who were given the all-clear after standard HIV tests, were actually in the acute stage of the infection. A study in Johannesburg found that similar figures - one in 200 people attending an STI clinic - were being falsely diagnosed as HIV-negative. Detecting hyperinfectious individuals and intervening to prevent them from spreading the virus during that time - and hopefully in the future - could have a major impact on the spread of the epidemic. FEMALE CONTROLLED METHODS OF PROTECTION The diaphragm is an old contraceptive technology doing new work as a prevention tool. By covering the woman's cervix, it appears to protect the cells in that region, where many female HIV infections occur. Research is underway in Zimbabwe and South Africa into the diaphragm, which has the advantage of being female-controlled. Unlike male and female condoms, women's partners do not have to know that a diaphragm is being used. A problem with barrier methods, such as the diaphragm and condom, is that they are of no use to a woman who wants to have children, yet still protect herself against HIV. This is where microbicides, substances which women insert into the vagina before sex, have a role to play. This year has seen the launch of the world's largest microbicide trial, with 10,000 women in South Africa, Tanzania, Uganda and Zambia taking part in the study. It has been estimated that if 20 percent of women in 73 developing countries used a microbicide that was just 60 percent effective, it would prevent 2.5 million new infections over three years. Microbicides are a very female-friendly intervention because women can use them without the knowledge or approval of male sexual partners. The hope is to develop contraceptive and non-contraceptive forms, so that women will be able to control their reproductive choices, as well as their health. Microbicides could also protect them against other sexually transmitted infections, in contrast to more targeted interventions like vaccines. After years of lagging behind in the funding stakes, microbicides appear to be making headway, with several big international trials taking place. South African researchers are optimistic that first-generation products will be commercially available in about five years. VACCINES - A SILVER BULLET? Although approximately 30 human clinical trials of an HIV vaccine are being conducted, there is unlikely to be a publicly available vaccine within the next decade, or even two. Part of the problem in creating vaccines is the mutability of the virus, which means that different clades (subtypes) dominate in different parts of the world. Scientists fear that a vaccine that works against one clade may not be successful against another. Researchers are also handicapped by the fact that they cannot ethically use weakened but live HIV in their vaccines for fear of infecting trial participants. The first two large-scale efficacy trials into an HIV vaccine finished in 2003, with both vaccines failing to prove their worth. Efficacy, or stage III, trials are the final testing stage and require large numbers of volunteers. Increasingly, researchers from, and in, developing countries are participating in vaccine trials - five years ago only one African country had carried out such a test; today nine are involved. South Africa has seen the start of its first Phase II (extended safety) clinical trials. But the problem with all bio-medical interventions is that unless they are almost 100 percent effective and permanent, they can lose effectiveness over time. Prevention technologies have to counter not only the virus, but also the human tendency for people to assume they are safe, and pursue risky behaviours that might otherwise have been avoided.