POTENTIAL IMPACT OF LOW EFFICACY HIV-1 VACCINES IN POPULATIONS WITH HIGH-RATES OF INFECTION

A safe and effective HIV vaccine to prevent infection and/or to modera te disease is urgently needed. Research progress has been slower than anticipated for a variety of reasons including uncertainty over which immunogen to use (i.e.; recombinant subunit envelope proteins or whole HIV-1 products), confusion an which immunological markers best correl ate with protection, the relevance of the HIV-I chimpanzee model to in fection in humans and the significance of the rapid evolution of HIV-1 , with different clades of the virus emerging in different parts of th e world. However, what some would interpret as encouraging results, fr om Phase I and II trials of recombinant envelope glycoprotein vaccines , have raised the question of whether the time is right to start Phase III trials in humans with immunogens that may have low to moderate ef ficacy. By using mathematical models and data from epidemiological stu dies, we examine the potential impact of such vaccines within heterose xual communities with high rates of infection. Analyses suggest that i t will be difficult to block HIV-1 transmission even with very high le vels of mass vaccination. The cost of sustaining high levels of herd i mmunity with a vaccine of short protection duration is likely to be hi gh. However, assessments of impact over the long duration of an HIV-1 epidemic indicate that many cases of HIV infection and associated mort ality can be prevented by immunogens with efficacy of 50% or less and a five year protection duration. These analyses add some support to th e view that proceeding with Phase III efficacy trials may be appropria te in high HIV transmission regions even if the consensus opinion on p otential efficacy of the immunogen is that it will be low.