First case of long-term chronic HIV-1 remission without myeloablation
A single case of a patient in Brazil has suggested that long-term suppression of chronic HIV may be possible without myeloablation, according to a presentation at AIDS 2020.
The patient in question was a 35-year-old Brazilian male who was diagnosed with HIV in October 2012. At baseline, he was deemed to have chronic HIV infection judging by CD4+ T cell count (372 cells/μL) and viral load (20,221 c/mL). Antiretroviral treatment (ART) was initiated in December 2012 with azidothymidine (AZT)/lamivudine (3TC) plus efavirenz (EFV). In 2014, he began receiving a tenofovir disoproxil fumarate (TDF)/3TC/EFV regimen which led to a suppression of viral load to below detection limits.
In 2015, the patient was enrolled in the SPARC-7* clinical trial. This trial included males age 18–65 years on first-line ART with a viral load below detection limits for >2 years and CD4 nadir >350 cells/mm3. Five patients, including the patient in this study, received the highly intensive ART regimen of baseline ART plus dolutegravir (50 mg QD) plus maraviroc (BID) and nicotinamide (500 mg BID) given for 48 weeks. After 48 weeks, patients were maintained on their original ART treatment followed by analytical treatment interruption.
The patient was the only one of the 30 enrolled participants who experienced viral load blips during experimental treatment, occurring at weeks 16 (viral load below detection limits with target detected [<40 c/mL]) and 24 (56 c/mL).
Viral DNA indicated low-level positivity in peripheral blood mononuclear cells (PBMC) and rectal biopsy at baseline and at week 48. Antibody quantitation over time (RLU [S/CO] in duplicates) demonstrated a trend toward reduction over time, from 91.8 at baseline, 75.6 at week 12, 60.8 at week 24, 56.8 at week 36, and 58.0 at week 48.
The patient underwent analytical treatment interruption in March 2019, with HIV plasma viral load assessed every 3 weeks. The viral load remained below detection levels for 64.7 weeks. Total HIV DNA on PBMC was undetectable before and 57 weeks after treatment interruption.
“The most impressive result, in our opinion, was the deep decrease in the antibody titres during and after the study period and during analytical treatment interruption. There was no change in the Western blot profile and the anti-HIV rapid test became negative,” presented Dr Ricardo Diaz from the Universidade Federal de São Paulo in São Paulo, Brazil.
“Although still an isolated case, this might represent the first long-term HIV remission without myeloablation or stem cell transplantation. Further analyses such as viral cultivation and sequential HIV antibody profile and detection are ongoing,” he said.
It remains to be established if HIV competent reservoirs decrease due to synergistic effects of maraviroc and nicotinamide. It also needs to be determined if the absence of HIV DNA on PBMC and negative co-cultures after the study period were due to continuous and cumulative reservoir elimination by maraviroc and nicotinamide and a boost in cellular or humoral immunity by nicotinamide, queried Diaz.