Prolonged viral suppression with anti-HIV-1 antibody therapy.
Christian GaeblerLilian NogueiraElina StoffelThiago Y OliveiraGaëlle BretonKatrina G MillardMartina TurrojaAllison ButlerVictor RamosMichael S SeamanJacqueline D ReevesChristos J PetroupoulosIrina ShimeliovichAnna GazumyanCaroline S JiangNikolaus JilgJohannes F ScheidRajesh GandhiBruce D WalkerMichael C SnellerAnthony FauciTae-Wook ChunMarina CaskeyMichel C NussenzweigPublished in: Nature (2022)
HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4 + T cells 1 . Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells 2,3 . Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml -1 . Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- public health
- hiv aids
- hepatitis c virus
- hiv testing
- sars cov
- water quality
- magnetic resonance
- induced apoptosis
- clinical trial
- big data
- zika virus
- cell proliferation
- electronic health record
- gestational age
- dengue virus
- men who have sex with men
- human health
- oxidative stress
- smoking cessation
- artificial intelligence
- cell cycle arrest
- cell death
- global health