Step by Step
At CROI 2017, HIV remission studies focus on early antiretroviral therapy initiation
by Jeannie Wraight
This year marked the 24th annual Conference on Retroviruses and Opportunistic Infections (CROI). HIV “cure” and remission had a significant presence at this year’s conference with many abstracts and presentations focused on studies that are edging us closer, step by step, to the necessary knowledge and advances to end the HIV pandemic.
Several presentations and abstracts focused on HIV remission after cessation of antiretroviral therapy (ART). There have been several previously reported cases where individuals have started antiretroviral therapy, stopped therapy and did not experience a viral rebound for an extended period of time. Examples of this are the Visconti cohort [A&U, August 2015] and the participants of the SPAREC study [A&U, April 2016]. There have also been several cases in babies and children such as the Mississippi baby and the French teenager. All of these were cases where treatment was started very early after initial infection. Researchers believe that for some, initiation of ARVs during acute infection, may prevent the seeding of viral reservoirs.
There is also the case of the Argentinian woman [A&U, December 2014] who had been HIV-positive for several years before starting treatment, and who (as far as we currently know) remains in remission after stopping therapy nearly twenty years ago.
The Argentinian woman appears to be a very unique case of spontaneous remission and even a possible functional cure with no known reason. As such, results would be very difficult to purposely replicate through a clinical trial. However, research continues into early initiation of ARVs in hopes of reproducing the results seen in these other cases.
One such attempt was described in a study presented at this year’s CROI, which followed a cohort of eight individuals in Thailand. All eight (seven men and one woman) initiated therapy during acute infection. They remained on ARVs for a median of 2.8 years before treatment was discontinued. None of the study participants was able to achieve viral remission longer than those seen in people who started ARVs months or years after HIV infection, despite a much smaller viral reservoir.
The same variation in results has been seen in infants. Mixed results were seen in a study of infants at a South African hospital. ARVs were initiated up to fourteen days after birth. Researchers witnessed varying degrees of viral clearance. Study results found that “54% had declined to LOD [limit of detection] or TND [target not detected] of the assay.” Of the infants who achieved viral suppression by 6 months, thirty percent then tested HIV-negative by HIV PCR during follow-up.
The more studies that are performed on early ART followed by analytical treatment interruption, the more evident it becomes that the big question is: Why are some people able to achieve a prolonged viral remission and others aren’t?
One study looked at various biomarkers that may predict time to viral rebound in post-treatment viral control. In a study of forty-five participants in Amsterdam who stopped therapy after twenty-four or sixty weeks, cell-associated HIV-1 US RNA was found to correlate with duration of time to viral rebound. This may help to gain a better understanding of the potential for viral remission. It was also found that another biomarker, MS (multiply spliced) RNA, was a predictor of CD4 loss.
Therapeutic vaccines have been studied since the 1990s as a potential means of controlling HIV. Researchers are now looking at therapeutic vaccines as one part of a potential cure regimen. After HIV is suppressed in the blood with ARVs, a drug would be given to “awaken” latent HIV, hiding in viral reservoirs activating the latent virus. A therapeutic vaccine would “prime” the immune system to better control and eliminate HIV by eliciting stronger and more effective immune responses.
Fifteen individuals participated in an early ARV, treatment interruption study of a therapeutic vaccine known as “the Spanish Vaccine.” The participants had been rolled over from a previous study that began them on ARVs within three months after HIV infection and where they were given a single dose of the MVA.HIVconsv vaccine. They remained virally suppressed on ARVs for three to four years, at which time they were given another dose of the vaccine, one dose a week for three weeks of romidepsin, and a second shot of the MVA.HIVconsv vaccination. ARV treatment was discontinued in thirteen of the fifteen participants.
Thirteen participated in treatment interruption, seven of which had to resume ART within four weeks due to viral rebound. Five participants remain off ART after seven, twelve, fourteen, and twenty-two weeks. The study is ongoing.
Researchers had originally hoped that the bursts of virus from romidespin would decrease the size of the reservoir, but that was not the case. However, activation of the latent virus appears to have helped to strengthen the CD8 responses of the vaccine.
Although these studies focus on just one group of HIV- positive people—newly infected—they are important to our overall understanding of HIV reservoirs and immune responses.
Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody.com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.