Very early introduction of ART may alter HIV immune response long term, with implications for development of effective vaccine.
The scientific community understands that when it comes to HIV treatment, earlier initiation is better. Now, a study conducted by investigators at the Ragon Institute of MGH, MIT, and Harvard reveals that extremely early introduction of antiretroviral treatment (ART)—ideally within a day or 2 of HIV diagnosis—may actually alter the course of the disease and enable the preservation of crucial CD4 T cells in infected individuals.
The investigators tapped a group of women enrolled in the FRESH (Females Rising Through Education, Support and Health) study in KwaZulu-Natal, Africa, which emphasizes career and life skills and offers HIV prevention strategies, treatment, and regular testing. Participants were sexually active women between the ages of 18 and 23 years, although all were HIV negative at the time of enrollment in the FRESH study.
The 46 Ragon Institute study participants were grouped into 3 cohorts. Group 1 consisted of 26 women in the FRESH study whose blood tests indicated that they were in the very earliest stages of HIV infection. This group was given ART right away, no more than 24 to 48 hours after diagnosis. Group 2 consisted of 8 participants whose HIV stage was slightly more advanced; this group also received ART immediately. The third group comprised 12 women in various stages of HIV infection who did not begin taking ART until the acute phase of infection had passed and their CD4 cell counts dropped below 350 cells/mm3, which was consistent at the time with South African guidelines for treatment.
Up until now, according to the investigators, there has been a lack of information about the impact of very early ART initiation on the CD8 cell response in HIV. When a person is infected with HIV, the body mounts an aggressive response using CD8 fighter cells. Unfortunately, the CD8 cell activity soon dies down and remains relatively ineffective. This leaves the virus free to proliferate and destroy valuable CD4 cells.
What the investigators found, however, is that by introducing ART as soon as possible after infection—before peak viremia—they can hijack this process: The initial surge of CD8 cells sent out to fight the virus is less aggressive when faced with ART, but the CD8 cells remain much more potent over the long term. This held true for both Groups 1 and 2 in the study, whose subjects continued to produce disease-fighting cytokines, leading to “the development of long-term immune memory,” according to senior author Bruce Walker, MD, who was quoted in a statement issued by Massachusetts General Hospital.
The study was designed to allow the investigators to look at the mechanics of how a recently infected person responds to HIV, without the typical immune destruction that occurs when ART initiation is delayed, and has implications for the creation of an effective HIV vaccine, the investigators said. “This study shows that the key benefit of initiating cART very early is the generation of transcriptionally quiescent immune responses,” the research team wrote. “It is plausible that the less stressed state of the responses in early [diagnosed] people could provide better immune priming amenable to rapid boosting with therapeutic vaccines.”
The study’s limitations include differences in the number of days between when the subjects were diagnosed with HIV and when their first sample was collected—a median of 28 days in Groups 1 and 3 and 25 days in Group 2—as well as the lack of tetramer analysis (which detects T cells) in certain samples. Increasing the sample sizes and doing more in-depth analysis may be ways to get around these barriers, the investigators wrote.
The Ragon Institute of MGH, MIT, and Harvard was founded with the purpose of creating a vaccine for AIDS. It continues to work toward this goal as the research community pursues a number of strategies to find a cure.