Abstract
Purpose Initiation of combination antiretroviral therapy (cART) during acute or early HIV-infection (AEHI) limits the size of the viral reservoir and preserves immune function. This renders individuals who started cART during AEHI promising participants in HIV-cure trials. Therefore, we established a multicentre prospective cohort study in the Netherlands that enrols people with AEHI. In anticipation of future cure trials, we will longitudinally investigate the properties of the viral reservoir size and HIV-specific immune responses among cohort participants. Participants Participants immediately initiate intensified cART: dolutegravir, emtricitabine/tenofovir and darunavir/ritonavir (DRV/r). After 4 weeks, once baseline resistance data are available, DRV/r is discontinued. Three study groups are assembled based on the preparedness of individuals to participate in the extensiveness of sampling. Participants accepting immediate treatment and follow-up but declining additional sampling are included in study group 1 ( € standard') and routine diagnostic procedures are performed. Participants willing to undergo blood, leukapheresis and semen sampling are included in study group 2 ( € less invasive'). In study group 3 ( € extended'), additional tissue (gut-associated lymphoid tissue, peripheral lymph node) and cerebrospinal fluid sampling are performed. Findings to date Between 2015 and 2020, 140 individuals with AEHI have been enrolled at nine study sites. At enrolment, median age was 36 (IQR 28-47) years, and 134 (95.7%) participants were men. Distribution of Fiebig stages was as follows: Fiebig I, 3 (2.1%); II, 20 (14.3%); III, 7 (5.0%); IV, 49 (35.0%); V, 39 (27.9%); VI, 22 (15.7%). Median plasma HIV RNA was 5.9 (IQR 4.7-6.7) log10 copies/mL and CD4 count 510 (IQR 370-700) cells/mm 3. Median time from cART initiation to viral suppression was 8.0 (IQR 4.0-16.0) weeks. Future plans The Netherlands Cohort Study on Acute HIV infection remains open for participant enrolment and for additional sites to join the network. This cohort provides a unique nationwide platform for conducting future in-depth virological, immunological, host genetic and interventional studies investigating HIV-cure strategies.
| Original language | English |
|---|---|
| Article number | e048582 |
| Journal | BMJ Open |
| Volume | 11 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 29 Nov 2021 |
Bibliographical note
Funding Information:Competing interests GdB has received grants through her institution from Bristol-Meyer Squibbs and Mac Aids Fund; honoraria to her Institution for scientific advisory board participations for Gilead Sciences and speaker fees from Gilead Sciences and Takeda. PR has received grants through his institution from Gilead Sciences, Janssen Pharmaceutica, ViiV Healthcare and Merck; honoraria to his institution for scientific advisory board participation for Gilead Sciences, ViiV Healthcare, Merck and Teva. CR has received study grants from AIDSfonds, ZonMW, Dutch Federation Medical Specialists, Merck, Janssen-Cilag, Gilead and ViiV Healthcare. All other authors declared no conflicts of interest.
Funding Information:
Funding The H-TEAM initiative is being supported by Aids Fonds (grant number: 2013169), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712), M.A.C AIDS Fund.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
