SIR

Your News story 'HIV trial doomed by design, say critics' (Nature 448, 110–111; 2007), portrays a biased and excessively pessimistic view of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial. As the first microbicide trial to be initiated from, and partially funded by, South Africa, the CAPRISA 004 trial promises to address some fundamental questions about the safety and effectiveness of tenofovir as a microbicide gel.

More published data exist on tenofovir for HIV prevention than for any other microbicide; thirteen monkey and four human tenofovir studies were considered when designing the CAPRISA 004 trial.

In the rural South African community where CAPRISA runs a large AIDS treatment programme, women with migrant partners account for most new HIV infections. The CAPRISA 004 trial and its episodic dosing strategy of two doses in 24 hours, one before and one after intercourse, was designed to maximize product adherence and hence the presence of tenofovir at exposure, especially for women with migrant partners.

This dosing strategy was selected after extensive consultation with international scientific experts, including those knowledgeable about microbicides, tenofovir and clinical-trial design. Just as importantly, it followed detailed consultation with the communities involved. Moreover, to assess the effectiveness of this strategy, extensive data will be collected on gel use, timing of gel use in relation to intercourse, adherence to the dosing regimen and tenofovir levels.

Differences of opinion and interpretation of data are important in science, including research on women-initiated HIV prevention, as you note in your Editorial 'Transmission lines' (Nature 448, 225–226; doi:10.1038/448225b 2007). But in the absence of a marker that can show whether a particular agent, dosing strategy or trial design will lead to protection against HIV, only the trial results will reveal the truth.