Clinical trial NCT04385875: Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study)
Official title: Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Keywords: HIV-1 infection
Therapeutic Vaccines
HTI
Antiretroviral Treatment Interruption (ATI)
Viral control
Lead sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Sponsor class: OTHER
Collaborators: name: Aelix Therapeutics
First posted: 2020-05-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants of the AELIX-002 clinical trial were randomly allocated to one of the following arms:

* Vaccine: DNA.HTI at weeks 0, 4, and 8 and MVA.HTI at weeks 12 and 20 (DDDMM) followed by ChAdOx1.HTI at weeks 0 and 12 and MVA.HTI at week 24 (CCM), starting at least 24 weeks after MVA.HTI week 20.
* Placebo: Normal saline solution at weeks 0, 4, 8, 12, and 20 (PPPPP) followed by normal saline solution at weeks 0, 12 and 24 (PPP), starting at least 24 weeks after week 20 administration.

ATI_extension will keep allocation from AELIX-002 for a separate description of the results.
Primary purpose: OTHER

Brief summary: The AELIX-002 trial has been conducted on a cohort of individuals who started cART within the first 6 months after the primary VIH infection, thus increasing the likelihood of observing a certain rate of post-treatment controls (PTC), regardless of treatment efficacy. Although the kinetics of HIV rebound should allow observing differences between placebo and control regarding the post treatment controls rate in case of efficacy of the IMPs, assessing the length and determinants of a post-intervention control (PIC) (i.e., associated with vaccination) beyond 24 weeks is crucial for developing a curative approach to HIV infection. In this regard, an extension of the ATI phase for those individuals with pVL less than 2,000 copies/mL after 24 weeks of ATI in the AELIX-002 offers an unique research opportunity to better understand relevant aspects of the mechanisms involved in the different phenotypes of a PIC and PTC.

Detailed description: The AELIX-002 trial has been conducted on a cohort of individuals who started cART within the first 6 months after the primary VIH infection, thus increasing the likelihood of observing a certain rate of post-treatment controls (PTC), regardless of treatment efficacy. Although the kinetics of HIV rebound should allow observing differences between placebo and control regarding the post treatment controls rate in case of efficacy of the IMPs, assessing the length and determinants of a post-intervention control (PIC) (i.e., associated with vaccination) beyond 24 weeks is crucial for developing a curative approach to HIV infection. In this regard, an extension of the ATI phase for those individuals with pVL less than 2,000 copies/mL after 24 weeks of ATI in the AELIX-002 offers an unique research opportunity to better understand relevant aspects of the mechanisms involved in the different phenotypes of a PIC and PTC.

This trial will enrol participants of the AELIX-002 clinical trial regardless of whether they received vaccines or placebo, who reach 24 weeks of ATI with pVL \<2,000 cop/ml and are willing to remain off cART. After accepting participation, subjects will undergo a one-year extension \[48 weeks\] of ATI monitoring (total duration of ATI envisioned will be of 72 weeks \[24 weeks in AELIX-002 study + 48 weeks in current study\]), followed by 24 weeks of safety follow-up after cART is resumed.

The primary objective of this study is to assess the safety and durability of viral control after AELIX-002 clinical trial intervention beyond 6 months of ATI. Furthermore, the study will collect biological samples to be stored for further investigational studies.

Eligibility criteria: Inclusion Criteria:

* Participants of the AELIX-002 clinical trial at week 24 of ATI:

  1. Willing to continue the ATI up to 1 year.
  2. With pVL \<2,000 copies/ml at week 24 of ATI on the AELIX-002 study.
  3. CD4 count ≥350 cells/mm3 at week 24 of ATI on the AELIX-002study.
  4. Willing to comply with the measures to prevent HIV transmission and reinfection required by the protocol.
  5. Available for follow-up for the planned duration of the ATI period of this study.
  6. Willing to accept blood draws and collect stool at time points specified in the Schedule of Procedures.
  7. If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device

     (IUD), or anatomical sterility in self or partner1) during the ATI and until her pVL is \<50 copies/ml after cART resumption.
  8. If heterosexually active male; using an effective method of contraception (anatomical sterility in self) or agree on the use of an effective method of contraception by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical

     sterility1) during the ATI and until his pVL is \<50 copies/ml after cART resumption.
  9. Not willing to donate blood during the study.
  10. Participants who understand the information provided, in the opinion of the investigator.

      Exclusion Criteria:

  1- Pregnancy or breastfeeding.

  2. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.

  3. Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study.

  4. Active hepatitis B or C at week 24 of ATI on the AELIX-002 study.

  5. Risk of HIV transmission (i.e. repeated STI during the AELIX-002 ATI period or reported unprotected anal sex).

Primary outcomes:
measure: Percentage of participants with viral remission
timeFrame: week 72
measure: Percentage of participants with viral control
timeFrame: week 72
measure: Time to viral detection
timeFrame: up to 72weeks after start of ATI
measure: Time to viral rebound
timeFrame: up to 72 weeks after start of ATI
measure: Percentage of participants who remain off cART
timeFrame: Week 72
measure: Time off cART
timeFrame: From ATI start to week 72
Secondary outcomes:
measure: Phenotypes characterization
timeFrame: From ATI start to week 72
measure: Change in a score for ATI psychological impact
timeFrame: At weeks 24, 48 and at week 4 post cART resumption (or at the End of ATI visit in case of early withdrawal).
measure: The proportion of participants who develop symptoms compatible with acute retroviral syndrome.
timeFrame: From ATI start to week 72
measure: The proportion of participants who suppress pVL to <50 copies/ml
timeFrame: 24 weeks after cART resumption
measure: The proportion of participants who develop new mutations not present in the pre-cART genotype
timeFrame: 24 weeks after cART resumption
measure: Description of participants who develop AEs related to the prime- boost regimen during this extension of ATI period.
timeFrame: From ATI_extension start to week 72
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
References: