Two large-scale studies of T-20 (enfuvirtide, Fuzeon) in treatment-experienced people have indicated that the addition of T-20 to antiretroviral salvage regimens enhances reductions in HIV-1 viral load. It is not active against HIV-2.

TORO 1 (conducted in the United States, Canada and Brazil) and TORO 2 (conducted in Europe and Australia) were similar studies involving about 1000 people in total. The participants had experienced failure of drugs in each of the existing classes and underwent resistance testing to select an ‘optimised background therapy’. In addition, two-thirds of the participants were randomised to receive T-20. In both studies, intent-to-treat analysis showed significantly greater reductions in viral load among those taking T-20^[1][2].

Adding T-20 to an effective background regimen produces the strongest and most enduring virological response. A recent analysis has shown that even adding T-20 to a background regimen consisting of drugs to which the patient is resistant reduced viral loads in the first four weeks of the study. However, it is clear that a background regimen including drugs to which the patient’s virus is susceptible is required for the best chances of virological success^[3][4]. The results of TORO 1 showed that phenotypic resistance testing has an important role to play in the optimisation of T-20 salvage regimens. This raises questions about whether it is appropriate to delay use of T-20 until patients have failed a number of different antiretroviral drugs.

Current guidelines from the British HIV Association (BHIVA) advise that T-20 should be used with two or more other active drugs, rather than as an add-on to a failing regimen, in order to reduce the chance of resistance developing. However, they also point out that it is substantially more expensive than any other antiretroviral drug^[5].

Longer-term follow-up of the TORO studies has confirmed the virological and clinical benefit of adding T-20 to a salvage regimen. After one year, people who took T-20 in addition to an optimised regimen were more likely to have a significant reduction in viral load and undetectable viral load, as well as a greater increase in CD4 cell counts and longer mean survival^[6]. Recent data have also shown that T-20 is still effective in around a quarter of patients after two years’ follow-up^[7].

A recent analysis of the health-related quality of life measures of participants in the two TORO studies has revealed that addition of T-20 to an optimised background regimen does not adversely affect any aspect of quality of life, and may improve general health and mental health status^[8].

T-20 has also been mooted as a useful component of post-exposure prophylaxis. In particular, a group of Italian doctors has recommended that T-20 should be considered where the source of infection is a patient with resistance to multiple anti-HIV drugs. However, the suitability of T-20 is uncertain: although T-20 reaches effective levels in the blood sooner than other drugs because it is injected, it may be less well tolerated for the same reason^[9].

T-20 penetrates poorly into the semen, possibly allowing the development of drug-resistant virus^[10].

T-20 is equally effective in patients with HIV that preferentially uses the CCR5 receptor to enter CD4 T-cells, and those with both CCR5 and CXCR4-using HIV, in terms of viral load reductions and increases in CD4 cell counts^[11]. There is also some evidence that T-20 is effective against HIV from group O, which is common in central Africa, despite being designed to block group M sub-type B strains. This suggests that T-20 has broad antiretroviral activity^[12].