Very Early Treatment Benefits and Possible HIV Eradication
From the "Berlin Patient" to the "Mississippi Baby," we're gaining an appreciation for the possible benefits and utility of very early antiretroviral therapy (ART). Several studies at CROI 2014 explored this subject. In a study of HIV infection using a mouse model, starting treatment six hours after exposure resulted in dramatically lower levels of HIV viral DNA in tissues. In a large human study, ART at very early stages of infection appeared to prevent, delay or even reverse the emergence of HIV antibodies in plasma even 12 weeks post-infection. Evolution of HIV antibodies was completely inhibited in four of four patients treated at Fiebig I stage (when HIV RNA is detectable, but viral antigen or HIV antibodies are not).
We learned that the "Mississippi Baby" (now "Mississippi Child") continues to have undetectable HIV RNA or proviral DNA and remains HIV negative 23 months off ART. Moreover, we were told that the "Mississippi Baby" may have a spiritual sibling, a California baby who was perinatally infected and treated at 4 hours of age. This youngster remains on ART, but is HIV seronegative and has both undetectable proviral DNA and infectious virus recovery at 9 months of age.
These two cases suggest that very early ART in infected newborns may prevent the establishment of an HIV reservoir and eradicate HIV infection. The key could be the absence of memory cells in newborns, which prevents the establishment of latent infection. This could open the door to avoiding HIV infection in newborns of HIV-positive mothers who were not on treatment during pregnancy.
While we have two babies in the U.S., we could have thousands in low- and middle-income countries, and this could have huge implications. Children were the first to prove fully the prevention of transmission with antiretrovirals, and they will also probably be the first to prove HIV eradication as well. The studies of these two girls have manifold implications for updating the very conservative treatment guidelines for the prevention of mother-to-child transmission of HIV where three-drug therapy is not the norm. We should move forward quickly to validate these findings and open the very big door to cure all of the roughly 400,000 HIV-infected newborns around the world each year.
Which other studies presented at CROI 2014 will have lasting impact? Read more of Dr. Llibre and Dr. Young's top picks.