Two and a half decades of research have produced increasing returns in combating the HIV/Aids epidemic, with dramatic improvements in treatment and greater awareness of potential ways to stop the spread of the virus. What has not kept pace is the ability to get these medical interventions to people in need. No matter how powerful a drug or a procedure is, it is useless to those who cannot access it. The HIV/Aids pandemic has social and economic drivers that also need to be factored into interventions.
Circumcision
Barring the post-coital shower, male circumcision has been the hottest topic in HIV prevention in the past year or so. A study conducted in Orange Farm outside Johannesburg found that circumcising men reduced their chances of catching HIV by about two-thirds.
Further research in Uganda and Kenya confirmed the effectiveness of removing male foreskins, which contain high levels of cells preferentially targeted by HIV, and create a micro climate for this and other sexually transmitted infections. This month saw United Nations’ agencies urge countries with high HIV prevalence to offer male circumcision as part of a package of prevention strategies, including counselling to remind men and their partners that circumcision only offers partial protection.
A question hangs over the extent of behavioural disinhibition — increase in sexually risky behaviour — that might occur when men believe they are safer from HIV and whether it will outweigh the protective effects over time.
Although the procedure confers a significant degree of protection, there are potential problems. In particular, men who have sex before their wound has fully healed appear to be at higher risk of transmitting and contracting HIV.
Research is ongoing into the benefits and potential risks of male circumcision, both for the men and for their sexual partners. There is a vocal and sometimes highly emotive anti-male circumcision lobby that questions the ever-growing evidence of the benefits of the procedure.
Antiretroviral therapy
They don’t cure HIV, but antiretrovirals (ARVs) have become ever more successful at extending people’s lives. Recently a Danish study found that a 25-year-old starting ARV treatment has a life expectancy of 35 years. The development of new drugs is reducing side effects and the ‘pill burden†— the number of pills that must be taken each day — which makes it easier for people to adhere to therapy.
Until relatively recently there were just three classes of drugs and resistance to one often meant a degree of resistance to the whole group.
There is now a host of new ARVs in the pipeline, including many that affect the life cycle of the virus at different stages. This means they are not affected by any resistance to older medicines that may have developed.
The discovery that a genetic mutation renders some people virtually immune to HIV, because it prevents HIV from attaching to the CCR5 receptors on cell surfaces, has led to research into CCR5 inhibitors.
Delivery of paediatric ARV treatment has lagged behind, even though children often show dramatic responses to the drugs. In the United States about 98% of HIV-positive children are expected to live to adulthood, and to have life spans close to those of their uninfected peers. In some areas of Africa half of HIV-positive infants are expected to die before they turn two.
Fewer ARVs are registered for paediatric use, partially because of ethical concerns about conducting clinical trials on children. While there is a huge need for paediatric ARVs in developing countries, the market in developed countries is small because prevention measures mean that few infants are infected with HIV via their mothers.
Prevention of mother-to-child transmission
Mother-to-child transmission of HIV (MTCT) from pregnant and breastfeeding mothers to their infants has created a paediatric HIV epidemic. Worldwide it is thought that MTCT was the cause of most of the estimated 700 000 new HIV infections of children in 2005. But in developed countries MTCT has almost been eradicated by a combination of multiple ARV drugs, Caesarean deliveries and avoidance of breastfeeding.
Attention is now focusing on the merits and demerits of starting pregnant women on antiretroviral therapy (ART) earlier than non-pregnant women.
Research is also being done into potential benefits of offering short-term ART during pregnancy, and breastfeeding, to women who may be too healthy to need to start lifelong therapy. HIV transmission occurs through breastfeeding, but the alternative of formula feeding is often hazardous to infants because of the much greater risk of infection from inadequately sterilised equipment and water. Recent research from South Africa has confirmed that exclusive breastfeeding of children by HIV-positive mothers — meaning the infant receives no other fluids or solids — can reduce the chances of the child catching HIV and cut illness and death from other infant killers such as diarrhoea.
Tuberculosis
HIV/Aids has contributed to the spread of the active tuberculosis (TB) epidemic, which, in turn, has become the biggest opportunistic killer of people with HIV in South Africa. The continued spread of multi-drug resistant TB and the emergence of its more intractable derivative, extensively-drug resistant TB, is, in part, due to high levels of HIV/Aids. Most South Africans have latent TB, which activates when the immune system is sufficiently weakened. Inadequate diagnosis, treatment, facilities, and monitoring services mean that many people fail to successfully complete the initial six-month TB treatment, which can lead to drug resistance.
Although research is under way for better diagnostic tests, vaccines, and antibiotics against the bacillus, the cupboard is still relatively bare at a clinical level, compared with the amount of resources available against HIV.
As a result much work is being done on improving the use of existing technologies and medicines. In particular, healthcare workers are looking at improving the continuum of care between TB and HIV services so that people co-infected with the two pathogens are treated and monitored effectively and with minimum disruption to patients’ lives.
Vaccines
Much hope is pinned on the creation of vaccines that prevent the spread of HIV, but the appearance of a commercially available intervention is years away. A sign of the difficulty facing researchers, and the magnitude of the epidemic, is that a vaccine would be considered good enough for use if it were just 30% effective in preventing new infections.
Part of the problem is the length of time needed to run clinical trials to test the safety and efficacy of a vaccine. The vaccines being trialed now are based on knowledge of the virus and the immune system that existed several years ago. Current cutting-edge research is only going to be translated into large-scale human-efficacy trials years down the line.
The South African Aids Vaccine Initiative lists eight clinical trials in South Africa, including Phambili, the country’s first large-scale HIV vaccine test. The researchers hope the vaccine will trigger a sufficient immune response to wipe out potential HIV infections before they are able to settle into a new host. Alternatively, or additionally, the vaccine may be able to slow progression of HIV infection into Aids once people are infected.
Microbicides
Microbicides are a female-centred approach because of the power they could allow women over their reproductive health. Creating microbicides has proved more difficult than expected with two particularly severe setbacks.
Earlier this year a multinational clinical trial into the Ushercell microbicide, which included sites in South Africa, was stopped prematurely after it appeared that the anti-HIV gel may have increased the risk of infection among women. Researchers are still trying to understand these findings, because the gel had passed previous safety tests in humans.
Microbicides, which can take the form of gels, creams, films, sponges, or devices that release the active ingredients, are nicknamed ‘chemical condoms†because many were designed to create a physical barrier against HIV within the vagina. Later generation microbicides, such as vaginal rings that slowly release an antiretroviral, are designed to target the virus itself.