Instant Expert: Defeating HIV-New Scientist Magazine

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Instant Expert: Defeating HIV
03 September 2011

While there are good treatments for HIV, we have failed to devise effective ways of stopping new infections. Vaginal gels to block the virus during sex are some years off, and a vaccine is still remote. Of the other prevention methods available, none has a 100 per cent success rate. Partial protection could paradoxically raise transmission, by giving people false confidence and thus encouraging unsafe sex.

Prevention today

If vaccines and vaginal gels are still some years away, what can we do in the meantime? Supplying drug users with clean needles is a cheap way of slashing new infections among drug users. When it comes to sex, people should use condoms every time, according to the public health establishment. But lots of people don't, so we should be providing better information so people can make more nuanced choices. Among gay men, for example, transmission is less common when the infected person is the receptive partner in anal sex. Yet we do little to publicise this fact as it is at odds with the mantra of "use condoms every time".

There is good evidence that male circumcision cuts transmission by up to 60 per cent, at least for straight men in areas where HIV is rife, such as in sub-Saharan Africa. The foreskin is rich in cells that act as efficient receptors for HIV. Circumcision does not appeal to all, but it has the advantage of being a cheap and easy one-off procedure. It has been promoted among adult men in some African countries with high rates of HIV, and uptake has been enthusiastic. Circumcision is less likely to be effective for gay men, since it does not protect the receptive partner and many gay men switch between roles.

Existing anti-HIV drugs are being investigated as a method of preventing transmission in two different ways. One approach is for people who are HIV-positive to start taking the drugs while their CD4 count is still high, before they would need treatment for the sake of their own health. The drugs reduce the amount of virus in their body fluids, making it harder to pass on the virus. An earlier start to treatment seems to cut transmission by an impressive 96 per cent, at least within a clinical trial.

But there are other factors to consider. Widespread early treatment could promote the idea that unprotected sex is less risky and thus reduce condom use. Early treatment cannot stop transmission from people who are newly infected, unaware of it, and therefore not taking drugs - and also in their highly infectious first few weeks. Reduced condom use would also lead to a rise in other sexually transmitted infections, causing spikes in HIV infectiousness even for those on treatment. Over many years, even occasional spikes mean lots of opportunities for transmission. So overall, early treatment might actually lead to more new infections.

The second way drugs can be used as a form of prevention is when those taking them are uninfected, in so-called "pre-exposure prophylaxis" or PREP. This has had mixed results. Three trials have shown it works, in both gay men and straight people, but earlier this year, a trial in straight women in Africa had to be stopped early, because it was not preventing infections.

The approach has other problems. The trial showed that many people don't take their drugs daily, and that raises the chance that resistant strains of HIV will develop and spread - ones that won't respond to some of our most common treatments. PREP raises financial and political challenges too. Can we afford to put uninfected people on daily therapy just so they can have unprotected sex, especially when some infected people still don't have access to the drugs they need?

Vaginal gels to block HIV

Researchers are trying to develop microbicides, gels or pessaries used in the vagina or rectum that reduce the transmission of HIV during sex. They are politically popular because, unlike male condoms, they give women some control over protecting themselves from HIV.

The problem is finding something that works. Several compounds block HIV in the test tube, but fail to protect women in real life. Some have even increased infections, probably because they damage the vagina, allowing virus to reach immune cells in the underlying tissue.

Then last year a large trial showed that a microbicide based on the anti-HIV drug tenofovir gave some protection. Infections were cut by 39 per cent overall, and by 54 per cent in women who used the gel at least four out of five times they had sex.

The formulation was not ideal; the gel had to be applied both before and after sex. But it's a boost for the field, and more products are in development using other drugs and formulations. For example, a vaginal ring has been developed that releases a drug continuously, and need only be changed once a month.

Vaccines

An effective vaccine is eagerly sought-after, so why has there been so little progress? Conventional vaccines use viruses that are either weakened or killed to trigger an immune response without causing disease. This is too risky with such a lethal virus as HIV. We first tried basing a vaccine on the main HIV surface protein, called gp120, to stimulate antibodies. But the key parts of gp120 are physically protected from antibodies by overhanging "decoy" components that have a high mutation rate, so such vaccines tend to provoke antibodies that are ineffective.

While antibodies target free viruses in blood or bodily fluids, the other branch of the immune system is T-cells, which kill other human cells infected with virus. More than a dozen vaccines in development are designed to provoke T-cell-based immunity but this approach had a big setback in 2007 after the failure of the first large trial. This tested a weakened cold virus carrying three HIV genes, designed to "teach" T-cells to destroy HIV-infected cells.

Then in 2009 positive results came out of a large trial in Thailand of a combination of two products. The first shot was a T-cell vaccine based on the canary pox virus, then people got boosters with a modified version of gp120, designed to provoke effective antibodies.

While the results were hailed as some much-needed good news for the field, the effect was weak: a mere 30 per cent fewer infections in those who were vaccinated compared with those who got placebo shots. Many suspect it could have been a statistical fluke, because of several puzzling features in the data. These included the vaccine's protective effect being inexplicably weaker in those who had the full course of shots than in those who only got some.

That's not to say we should give up on finding a vaccine. A few rare individuals have been discovered who seem to have natural immunity to HIV, which suggests that an effective vaccine is possible, at least in theory. Powerful "neutralising" antibodies have also been found in nature and immunologists are trying to design special snippets of gp120 that could be given as a vaccine to prompt the body to produce these same antibodies. But both these approaches are many years away from the clinic.