ARVs and HIV prevention in 2003

The use of antiretroviral drugs to prevent HIV transmission is now

widespread in many countries and settings. This is a situation in which a single drug at a relatively low dose, or dual therapy, may be preferable to using combination therapy. (There are precedents for this with other diseases. For example, isoniazid used to prevent latent TB becoming active TB, or low doses of antimalarial drugs used for prophylaxis.) To do this safely and on a large scale requires increased levels of access to voluntary counselling and testing, often including the use of rapid tests, to make sure that ARVs are not given inappropriately to positive people.

The one area where there can be no scientific argument about the efficacy of ARVs in prevention is mother-to-child transmission, although arguments about funding and services to deliver it will continue.

Other uses - such as provision of ‘post-exposure prophylaxis’ to health care workers accidentally exposed to blood during their work - are already widespread in Europe and the Americas and are likely to expand during 2003. This is happening despite lack of definitive proof that such treatment is effective and despite some doubts raised by animal studies (Benlhassan-Chahour; Le Grand).

Where feasible, and where the prevalence of HIV in the community justifies it, many health workers are now committed to extending the same option to people who have suffered rape or sexual abuse. At the International Conference on AIDS in Barcelona there were reports from Congo Brazzaville (Belanger), Thailand (Grisurapong), Brazil (Rosa), Argentina (Oliva; Perez) and the USA (Min; Salazar; Scaturro), and the provision of ARVs for this purpose is now official South African policy.

In 2003, new information from clinical trials of ARVs used to prevent adult infection may bolster or change these programmes and lead to urgent consideration of different models for HIV prevention. In particular, the emergence of tenofovir as an alternative to nevirapine or AZT/3TC for HIV prevention, may have profound effects on the way we think about using ARVs.

Mother to child transmission

Uptake of antiretroviral drugs (ARVs) to prevent mother-to-child transmission of HIV has been painfully slow, even where the drugs are provided free of charge. It is clear that the real barriers – including financial ones - are in the lack of access to voluntary counselling and testing, including private space in very busy public clinics, lack of training for health care staff, and - above all - a perceived lack of social support for women who test HIV positive.

At the same time as these problems are addressed, there must be a critical evaluation of the methods used to prevent HIV transmission. Clinical studies are already under way, to look at a series of issues with massive public health implications, including:

• the scope for using antiretrovirals, either given to HIV positive mothers as combination therapy or to HIV negative babies, to prevent breast milk transmission
• the added value of giving AZT/3TC for 4 days or 7 days to a newborn baby, in addition to treating the child with a single dose of nevirapine. Can this further reduce the risk of transmission and/or ensure that a baby which does become HIV positive does not have NNRTI-resistant viruses?
• the effect of single use of nevirapine on a woman’s ability to benefit from combination therapy including nevirapine or efavirenz, as and when she needs it
• the effect on viruses circulating in a community, of the use of nevirapine as a single agent to prevent mother-to-baby transmission.

The potential uses of tenofovir

The use of tenofovir to prevent transmission has stronger support, from animal studies, than the use of AZT/3TC and other combinations currently recommended for “post-exposure prophylaxis”. Can this transfer into clinical practice? We should begin to find out in 2003, and with Gilead's commitment to making the drug available at cost in least developed countries and at preferential rates elsewhere, this is likely to become a very hot area of research.

The most radical idea, which now has some research funding from the Bill and Melinda Gates Foundation, is to use the drug to protect adults against sexual exposure by offering it to HIV negative populations at exceptionally high risk.

A preliminary clinical trial has already been carried out, giving nevirapine regularly to HIV negative adults at risk of HIV, to establish the safety and feasibility of using low steady doses to prevent HIV infection (Jackson). Despite positive initial findings, there must be concerns both about side effects and the risk of exposure to resistant viruses, given that a single mutation is enough to make the virus resistant to nevirapine.

If it emerges that tenofovir, given at a low dose to HIV negative adults at high risk of HIV from sexual exposure, can substantially cut the risk of infection, then this is likely to be preferred to nevirapine on both counts. If the results in humans match those seen previously in animals, then a process of education and consultation with affected communities will be needed, that has no obvious parallels.

How can people weigh up the limited information we now have, about the risks

of this drug, against their personal risks of exposure to HIV?

Is this something to be considered as an option on a par with the use of oral contraceptives, or is it a medicalisation too far?