New protease inhibitor

Darunavir is a new protease inhibitor recently approved in Europe for treatment of people with HIV who have already experienced the failure of more than one protease inhibitor-containing drug combination.

The drug is being targeted at people who have already taken several HIV drug combinations.

In people with lots of treatment experience, it can be hard to achieve an undetectable viral load because of cross-resistance between drugs in the same class (eg between protease inhibitors).

Darunavir, which was designed to bind more tightly to the HIV protease `pocket` than other drugs in its class, is thought to have a much higher resistance barrier than other protease inhibitors, and so may be active in the face of high-level resistance to other drugs in its class.

People with resistance to numerous drugs have the best chance of successful control of HIV viral load if they can combine a drug in a new class with at least one other drug that is still fairly effective against HIV.

This makes darunavir an important potential partner for drugs in new classes, such as the imminent integrase and chemokine inhibitors, but also other classes in the pipeline such as maturation inhibitors.

A study published last week shows that darunavir is especially effective when it is used with a drug from a class which is new to the patient. In this study, the drug in a new class on offer was enfuvirtide (T-20, Fuzeon), the first HIV fusion inhibitor.

Fifty-eight per cent of people in the POWER 1 & 2 studies who combined enfuvirtide with darunavir had a viral load below 50 copies after 48 weeks on the combination, compared with 11% who did not receive enfuvirtide.

In another study reported recently, of the new integrase inhibitor raltegravir, showed that 90% of patients who received raltegravir with darunavir or enfuvirtide achieved a viral load below 400 copies/ml after 16 weeks, compared with 74% who received neither darunavir or enfuvirtide (T-20).

All these findings are very encouraging for people who are very treatment-experienced. They show that, in theory, people who may have very high levels of drug resistance are able to benefit from drugs in a new class if they can take darunavir, because that protease inhibitor can provide vital back-up.

What we know less about is how resistance emerges to darunavir in people whose viral load won’t fall below the limits of detection, and whether they lose the benefit of that drug quickly if it is just added to a combination of other drugs which have a weak effect on HIV.

This makes it all the more important for people who are highly treatment-experienced to consider using it with one of the drugs in a new class – either raltegravir (an integrase inhibitor), maraviroc (a chemokine inhibitor) or enfuvirtide (a fusion inhibitor). Enfuvirtide is already licensed; maraviroc and raltegravir are available through early pre-licensing access programmes in the United States and some countries in Europe (including the UK).

HIV transmission and the law

A man in Scotland was sentenced to nine years in prison last week for transmitting HIV and hepatitis C to his female partner.

It was the first time that anyone has been successfully prosecuted for the sexual transmission of hepatitis C, and the second successful Scottish prosecution for the sexual transmission of HIV.

There have now been a number of prosecutions in the United Kingdom for `reckless` HIV transmission. The prosecutions have caused widespread concern among HIV-positive people, doctors and people involved in HIV prevention, partly because of the nature of the scientific evidence being used to `prove` transmission, but also because of the stigmatising effect that such cases are having.

Next week NAM will publish a new book, Criminal HIV Transmission, aimed at individuals who work within – or are in contact with – the criminal justice system. Until now, no single resource has provided an overview of the issues; NAM’s new book aims to bride that gap. The book should be useful to anyone who requires up-to-date information in clear, layman’s language about the science – medical, clinical, social, epidemiological, and forensic – of HIV transmission as it relates to the criminal law.

Herpes and HIV transmission

HSV-2, the virus that causes genital herpes, greatly increases the risk of becoming infected with HIV in women, even when women who carry HSV-2 have no symptoms of genital herpes, a large study in Tanzania has found.

Genital herpes is a condition that may disappear after an initial attack, only to flare up later. It causes painful ulcers in the vagina, the anus or the penis, and may require treatment indefinitely, especially in HIV-positive people, in order to prevent reactivations.

Other studies have shown that Individuals with HSV-2 are more likely to acquire HIV infection and that recent infection with HSV-2 greatly increases the risk of HIV infection.

HIV-negative women without detectable genital ulcers caused by HSV-2 may nevertheless have microscopic ulcerations for a large proportion of the time, greatly increasing their risk of HIV infection.

HIV-positive women who receive daily anti-herpes treatment with the drug valaciclovir had lower levels of HIV in their genital fluids, implying a reduced risk of transmission.

Two studies in HIV-positive women using the anti-herpes drug aciclovir showed a modest reduction in HIV levels in genital fluids.

All these studies suggest that HSV-2 has a leading role in promoting vulnerability to HIV infection, especially in women, and that its suppression can reduce the risk of female-to-male HIV transmission.

In men who have sex with men, HSV-1 (the herpes virus which causes cold sores) also appears to increase the risk of becoming infected with HIV, although the reason for this is not well understood.

New from NAM