Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection

Abstract

BackgroundLimited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.Methods and FindingsWe prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24.At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm3. HIV RNA was 5.5 log10 copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/106 PBMC) vs. Fiebig I (8 copy/106 PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008).After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).ConclusionsGut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.

Challenges and potential barriers to the uptake of antiretroviral-based prevention in Asia and the Pacific region

“…82 However, little is known about acute and early HIV infection in Asia, with the exception of China and Thailand. Adding strategies for earlier detection of HIV-1 infection using pooled HIV nucleic acid amplification testing in antibody-negative blood samples from high-incidence populations of MSM was considered effective for intervening early with behavioural interventions and earlier treatment during a period with such a high transmission risk in Bangkok, Thailand, 83,84 and Lianing province, China. 85 …”

Post-treatment control of HIV infection

“…Latently infected cells are unaffected by ART, undergo homeostatic proliferation (14), and their population is established early after infection (15)(16)(17). Typical measurements of the reservoir size in chronically HIVinfected patients are in the range of 0.6-40 per 10 6 CD4 + cells (18).…”

“…In the VISCONTI study (1), treatment was initiated during primary infection, potentially limiting the seeding of the latent reservoir (16,27). Intriguingly, comparisons of integrated DNA in resting CD4 + cells between PTCs and ECs suggest that both sets harbor similar latent reservoirs in size and composition (1).…”

“…Treatment during primary infection is known to reduce latent reservoir sizes (16,27) and delay viral rebound upon cessation of treatment (5). A number of factors may play a role, including the size of the latent reservoir (1,2,30), the rate at which latently infected cells become activated, and the strength of the host immune response (7).…”

Infection par le virus de l’immunodéficience humaine

“…Ananworanich et al se sont intéressés à la fois à l'effet de l'intensification thérapeutique et à l'introduction précoce du TARV, dès la phase aiguë de l'infection. Dans cette étude, l'initiation, à la phase très précoce de l'infection, d'une pentathérapie, comprenant en particulier du raltégravir et du maraviroc, conduit à une réduction significative de la quantité d'ADN de VIH-1 au niveau du côlon sigmoïde [37]. L'impact de l'initiation précoce du TARV sur la taille du réservoir viral digestif a fait l'objet de plusieurs autres études chez l'homme (Tableau II).…”