Table 2.
Study Designs, Risk Types, and Likelihood and Nature of Benefit in 13 HIV Cure Consent Forms
| Study ID and type | Study design |
Number of risk types: top risk types (most lines of text); other key risk types (lines of text) |
Consent form statement on likelihood of benefit | Nature of benefit |
|---|---|---|---|---|
| 01 GTR | Phase I, infuse gene-modified cells back into participants, then introduce structured treatment interruption and monitor HIV viral levels | 11 risk types: Top: Adenoviral vector (30); reproductive (27); gene modified cells (23); apheresis (18) Others: Antibody formation (13); viral drift (10); excluded from future research (9); TI (7); blood cancer (7) |
“You should not expect any benefit. it is primarily designed to test safety.” | Genetically modified cells resistant to HIV and produce additional resistant cells |
| 02 GTR | Safety study, participants have stopped ART; three groups: no chemotherapy or two doses of chemotherapy, then infuse gene-modified cells and monitor HIV viral levels | 10 risk types: Top: Gene modified cells (52); busulfan (chemotherapy agent) (50); neupogen G-CSF (32); apheresis (21); infusion of modified cells (20) Others: Excluded from future research (6); no ART (4) |
“It is unusual for people who take part in an early trial like this to personally benefit from the experimental intervention.” | Improve immune system, reduce HIV in bone marrow and WBCs, WBCs live longer |
| 03 Vaccine | First-in-human, 5 groups: vaccine or placebo; vaccine+low dose IL-12 or placebo; vaccine+mid-dose IL-12 or placebo; vaccine+highest dose IL-12 or placebo; vaccine+highest dose IL-12 or placebo | 13 risk types: Top: EP procedure (34); pregnancy (33); HIV DNA vaccines (31); IL-12 plasmid (26); pDNA vaccine (13) Others: Unknown frequency or theoretical: include mutagenesis and autoimmune (12); placebo (6); randomization (4) |
“…there may be a direct benefit to you, but no guarantee can be made. It is possible you may get a treatment that will improve your immune response…and may control your viral infection better.” | Control viral load better, extra stimulation to form immune response to HIV |
| 04 Vaccine | Therapeutic intensification with two ART drugs, then randomized to either add or not add the vaccine intervention | 10 risk types: Top: Maraviroc (ART) (41); raltegravir (ART) (28); DNA vaccine (17); pregnancy (15); injection (8) Others: HLA typing (5); exclusion from future research (3); rAD5 vaccine and exclusion from future research (2) |
“If you take part, there will be no direct benefit to you.” | See if proviral DNA decreases, if immune response increases |
| 05 TI | After viral suppression, introduce treatment interruption and follow over time | 13 risk types: Top: [5 procedures are optional] Brain MRI (24); colonoscopy (17); spinal fluid (13); lymph noted biopsy (12); mucosal secretions (6); leukapheresis [required] (13) Others: Pregnancy (11); sexual transmission (9); virus not controlled (8); questionnaire and discomfort with questions (4); confidentiality (2) |
“It is possible that you will not gain any direct benefit from participating in this study.” | Changes in CD4 count and amount of virus over time |
| 06 TI | Phase I/II proof of concept study. After viral suppression, introduce treatment interruption and follow | 8 risk types: Top: Nevirapine (68); lopinavir/ritonavir (27); blood draw (12); taking 3 ARVs earlier than usual (7); Others: Stop ARVs (4) |
“This study may be of no direct benefit to your baby.” | Control amount of HIV in your baby's body |
| 07 Latency reversing | 3 dose groups of disulfiram (antialcohol drug), to reduce latent HIV infection, people on ART | 4 risk types: Antabuse (45); reproductive (27); phlebotomy (12); side effects would stop participation (3) |
“…study will not provide you with any direct benefit. It is hoped that it will reduce total amount of HIV in the body, but this may not happen. The intervention will not result in a cure.” | Reduce total amount of HIV in body; ultimate aim to develop cure for HIV, though likely to take many years |
| 08 Latency reversing | Pilot safety and efficacy study, vorinostat (VOR) given to reduce amount of dormant HIV in immune cells, people on ART | 6 risk types: Top: Vorinostat (33); contraception/pregnancy/breast feeding (14); sigmoidoscopy (9); other risks (8) |
“We cannot guarantee or promise that you will receive personal benefit…the study drug is not expected to cure you of HIV infection.” | Test if VOR may reverse HIV, reduce amount of dormant HIV in immune CD4 resting memory T cells |
| 09 Latency reversing | Study impact of valproic acid and/or Fuzeon [ART) on decreasing latent infection, people on ART | 7 risk types: Top: Enfuvirtide (Fuzeon-ART) (54); valproic acid (34); leukapheresis (24); pregnancy (23); unmask HIV (9) |
“Little chance you will benefit from being in the research study,” not expected to cure but “first step toward that far-away goal.” | Decrease cells infected with HIV; eradicate hidden virus, may someday eliminate HIV |
| 10 Latency reversing | Phase I/II placebo-controlled, dose escalation study of romidepsin to decrease latent infection, people on ART | 7 risk types: Top: Leukapheresis (28); pregnancy and infertility (24); romidepsin and could reactivate virus (10); blood draw (9) |
“Not designed to directly benefit you…it is extremely unlikely that a single dose of the study drug will lead to curing HIV.” | Virus should reproduce and new HIV will kill cells hiding to it |
| 11 Latency reversing | Phase I/II study of effect of vorinostat (VOR) on decreasing latent infection, people on ART | 8 risk types: Top: Vorinostat (58); pregnancy (27); leukapheresis (24); blood draw (9); detectable viral load (5) Others: Infertility (5); confidentiality (5) |
“There is little or no chance you will benefit from being in this study.” | Viral load changes after VOR |
| 12 Observ | Compartmental analysis: Enroll individuals on ART and measure drug and viral levels in gut and lymph tissues | 4 risk types: Lymph node biopsy (31); colonoscopy (22); anoscopy (12); blood draw (2) |
“No benefit is assured by participating in this study.” [Consent Form has no separate benefit section] | Measure drug and HIV levels in lymph nodes and gut after ART |
| 13 SCT Observ | Study of HIV reservoir dynamics and diversity: Enroll individuals post-stem cell transplant (SCT), optional collection of tissues and treatment interruption | 5 risk types: [3 procedures are optional] Analytical treatment interruption (40); rectal biopsy (30); cerebral spinal fluid sampling (22); leukapheresis (13); Nonphysical risks including return of results and not putting in EMR (17) |
“Taking part in this study may not make your health better…we hope information learned…will help doctors learn how to improve the control of HIV infection. However, there is no guarantee or promise that this will happen.” | Improve control over HIV |
GTR, gene transfer research; TI, treatment interruption; Observ, observational study; ART, antiretroviral treatment; WBC, white blood cells; IL-12, interleukin-12; ARV, antiretroviral.