None listed
Conditions
Interventions
HIV-1–infected from HVTN 704/HPTN 085 participants Type of group
HIV-infected participants undergoing an analytical treatment interruption after having received VRC01 or placebo infusions during the HVTN 704/HPTN 085 study.
Sponsors
INSTITUTO NACIONAL DE ALERGIAS Y ENFERMEDADES INFECCIOSAS DE LOS ESTADOS UNIDOS,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Estimated date of HIV-1 acquisition within 8 weeks of participant’s last HVTN 704/HPTN 085 infusion. 2. Initiated ART within 28 weeks of HVTN 704/HPTN 085 HIV-1 date of diagnosis. 3. Receiving continuous ART for at least 1 year 4. If on an NNRTI, willingness and ability to switch to a PI- or INSTI-containing regimen for at least 4 weeks prior to ART interruption. 5. Willingness to interrupt ART for up to 24 weeks or up to the time of meeting ART re-initiation criteria. 6. Willingness to re-initiate ART upon meeting study ART re-initiation criteria. 7. Willingness to use barrier protection (ie, male or female condoms) for all sexual activity until after confirmation of viral suppression following ART reinitiation 8. Willingness for CRS staff to contact primary HIV care provider to exchange information regarding HVTN 804/HPTN 095 and participant medical history. 9. Site investigator anticipates that a fully active alternative ART regimen could be constructed and would be available in the event of virologic failure on the participant’s current ART regimen. 10. Access to a participating CRS and willingness to adhere to study visit schedule and to be followed for the planned duration of the study. 11. Ability and willingness to provide informed consent. 12. Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to enrollment with verbal demonstration of understanding of all questionnaire items answered incorrectly. 13. Agrees not to enroll in another study of an investigational research agent for the duration of the participant’s trial participation. 14. HIV-1 infection, with reactive HIV-1 antibody and any Multispot or Geenius HIV-1/HIV-2 results, documented by the HVTN 704/HPTN 085 HIV diagnostic algorithm. 15. Plasma HIV-1 RNA ≥ 1,000 copies/mL by any assay, prior to initiating ART. 16. CD4+ cell count ≥ 450 cells/mm3 obtained within 90 days prior to enrollment. 17. One plasma HIV-1 RNA below the lower limit of quantitation (LLOQ) collected at each of the following: Note:Non-US sites must have results from locally available assays that are approved as standard-of-care by their regional governing bodies. 18. Hemoglobin (Hgb) ≥ 10.0 g/dL for volunteers who were assigned female sex at birth, ≥ 11.0 g/dL for volunteers who were assigned male sex at birth. 19. Absolute neutrophil count (ANC) ≥ 750 cells/mm3 20. Platelets ≥ 100,000 cells/mm3 21. ALT 60 mL/min/1.73m2. 23. Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit and prior to enrollment. Persons who are NOT capable of becoming pregnant due to having reached menopause (no menses for 1 year) or having undergone total hysterectomy or bilateral oophorectomy or tubal ligation (verified by medical records) are not required to undergo pregnancy testing. 24. Reproductive status: A volunteer who is capable of becoming pregnant must agree to consistently use effective contraception (see Appendix B and HVTN 804/HPTN 095 SSP) for sexual activity that could lead to pregnancy from at least 21 days prior to enroll
Exclusion criteria
Exclusion criteria: 1. Any plasma HIV-1 RNA ≥ LLOQ (LLOQ: 75, 50, 40, or 20 copies/mL) within 12 months prior to enrollment. Note: Non-US sites must have results from locally available assays that are approved as standard-of-care by their regional governing bodies. 2. History of AIDS-defining illnesses or US Centers for Disease Control (CDC) Category C events per the current list on the CDC website (see HVTN 804/HPTN 095 SSP). 3. Autoimmune disease, including Type I diabetes mellitus. 4. Immunosuppressive medications received within 6 months before enrollment. 5. Blood products received within 120 days before planned ART interruption. 6. Investigational research agents, other than experimental vaccine(s), received within 30 days before planned ART interruption. 7. HIV or non-HIV experimental vaccine(s) received within the last 1 year. 8. Licensed live attenuated vaccines received within 30 days before planned ART interruption (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine). 9. Licensed vaccines that are not live attenuated vaccines received within 14 days before planned ART interruption (eg, tetanus, pneumococcal, hepatitis A or B). 10. Significant or unstable cardiac or cerebrovascular disease (eg, angina, congestive heart failure [CHF], recent cerebrovascular accident [CVA], or myocardial infarction [MI]). 11. Hepatitis B surface antigen (HBsAg) or positive HCV RNA (Not exclusionary: positive HCV Ab with negative HCV RNA). 12. Pregnant or breastfeeding 13. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: • A process that would affect the immune response; • A process that would require medication that affects the immune response; • Any contraindication to repeated blood draws, including inability to establish venous access; • A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer’s health or well-being during the study period; or • Any condition specifically mentioned among the exclusion criteria. 14. Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, or a volunteer’s ability to give informed consent. 15. Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, could be exacerbated by events associated with protocol participation, which include: ATI, low-level viremia, subsequent viral rebound, and ART re-initiation. 16. HIV dementia or other neurologic disease that, in the judgment of the investigator, would be a contraindication to study participation. 17. Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years. 18. Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator’s judgment, has a reasonable assurance of sustained cure, or who is unlikely to experienc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Confirmed Viral load for HIV ≥ 200 copies/mL (ie, on 2 consecutive samples) CD4+ T-cell count < 350 cells/mm3 (ie, on 2 consecutive samples) Any HIV-related syndrome (eg, acute retroviral syndrome, an opportunistic infection) Pregnancy or breastfeeding ART re-initiation requested by participant • ART re-initiation requested by primary HIV care provider or CRS Investigator of Record (eg, if deemed medically necessary) Measure:Time to meeting criteria for ART re-initiation Frequency of sustained post-treatment HIV control, defined as ≥ 24 weeks off ART without meeting ART re-initiation criteria Laboratory measures of safety, adverse events (AEs), SAEs (serious AEs), and rates of discontinuation Timepoints:HIV viral load (CV) controls weekly from 0 to 8 weeks, every 2 weeks from 10 to 24 weeks and every 4 weeks from 28 to 52 weeks CD4 and CD8 lymphocyte count controls every 2 weeks from 0 to 8 weeks, every 4 weeks from 10 to 24 weeks and every 8 weeks from 28 to 52 weeks Hematological and biochemical controls every 4 weeks from 0 to 24 weeks and every 8 weeks from 28 to 52 weeks Clinical evaluation at each visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:immunogenicity and virological analysis (cellular and humoral immunity analysis, analysis of HIV deposits) Measure:Response rate, magnitude, and polyfunctionality of HIV-specific CD4+ and CD8+ T-cell responses as measured by flow cytometry Magnitude and breadth of neutralizing antibody (nAb) responses against autologous and heterologous HIV isolates, as measured by TZM-bl neutralization assay Non-neutralizing, FcγR-mediated antibody effector functions such as ADCC, ADCP, and virion capture Frequency of dendritic cell activation and maturation markers, as measured by flow cytometry or other cell phenotyping assays Frequency of T- and B-cell activation and exhaustion markers, as measured by flow cytometry or other cell phenotyping assays Timepoints:each 4 weeks upto 52 weeks | — |
Countries
Brazil, Peru, United States
Contacts
Public ContactPedro Augusto Gonzales
ASOCIACION CIVIL IMPACTA, SALUD Y EDUCACION
Outcome results
None listed