Background
Patients and methods
Trial design
Participants
Inclusion criteria
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HIV-positive MSM patients of ≥18 years of age who, at the time of study inclusion were not infected simultaneously by the four genotypes of HPV that the quadrivalent vaccine addresses.
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Patients who had a normal high-resolution anoscopy (HRA) at screening for inclusion or only had condylomas and/or low squamous intraepithelial lesion (LSIL) in anal biopsy.
Exclusion criteria
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HIV MSM patients who had simultaneous anal infection with the four genotypes addressed by the vaccine, and who at least had HPV genotypes 16 and 18.
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Active opportunist infection at the time of recruitment into the study.
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Patients who, in screening anoscopy had HSIL, or ASCC or had received treatment for these lesions (these patients were excluded because patients with HSIL have a higher probability of progression to ASCC).
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History of allergy to aluminium and/or yeast extract excipient.
Settings and locations
Data collection
Sample size
Randomisation
Statistical methodology
Descriptive analyses
Results
Study population: screening
Variables | HIV-MSM patients n = 162 |
---|---|
Mean age; years ±SD | 37.9 ± 10.2 |
Spanish, n (%) | 153 (94.2) |
Primary school, n (%) | 21 (13) |
Secondary school; technical school, n (%) | 53 (32.7) |
University, n (%) | 88 (54.3) |
Median months of sexual activity (P25–P75) | 216 (120–300) |
Median of anal-receptive sexual partners in previous 12 months (P25–P75) | 1 (1–5) |
Overall median number of sexual partners, (P25–P75) | 70 (20–250) |
Condom users, n (%) | 127 (78.4) |
Median percentage of condom use, (P25–P75) | 100% (50–100%) |
History of condylomatosis, n (%) | 47 (29) |
Current condylomatosis, n (%) | 48 (29.6) |
Syphilis treated, n (%) | 35 (21.6) |
Latent treated tuberculosis, n (%) | 10 (11.8) |
Chronic HCV infection, n (%) | 4 (4.7) |
Chronic HBV infection, n (%) | 1 (1.2) |
Smoking habit, n (%) | 33 (38.8) |
Ex-smoker, n (%) | 12 (14.1) |
Ex-IVDA, n (%) | 1 (1.2) |
Alcohol, median SUA, (P25–P75) | 1 (0–1) |
Prior AIDS diagnosis, n (%), 95% CI | 27.8 (45) |
Median time of HIV duration, months (P25–P75) | 57 (24.5–120) |
CD4 nadir, cells/µL, (±SD) | 337.8 (±205) |
Treatment naïve, n (%) | 14 (8.6) |
Median ART, months (P25–P75) | 37 (13–88) |
Median lines of ART, n (P25–P75) | 1 (1–2) |
Virological failure, n (%), 95% CI | 5 (3.3) |
Baseline CD4, cells/µL (±SD) | 688 (±256.4) |
Baseline CD8, cells/µL (±SD) | 976.5 (±399.4) |
Baseline viral load, log10 (±SD) | 3.74 (±4.5) |
Variables | n = 162 |
---|---|
HPV PCR positive, n (%) | n = 156 |
LR-HPV | 90 (57.7) |
HR-HPV | 71 (73.7) |
HR and LR-HPV | 76 (48.7) |
Vaccine genotypes, n (%) | |
HPV6 | 27 (17.3) |
HPV11 | 21 (13.5) |
HPV16 | 41 (26.3) |
HPV18 | 20 (12.8) |
HPV16 and HPV18 | 7 (4.5) |
HPV of the HPV16 species (31, 33, 35, 52, 58, 67) | 80 (50%) |
HPV of the HPV18 species (39, 45, 59, 68) | 59 (36.9%) |
Anal cytology, n (%) | n = 160 |
Normal | 62 (38.8) |
LSIL | 76 (47.5) |
HSIL | 9 (5.6) |
ASCUS | 13 (8.1) |
Anoscopy histology, n (%) | n = 162 |
Normal | 65 (40.1) |
LSIL | 74 (45.7) |
HSIL | 23 (14.2) |
ASCC | 0 |
Patients enrolled in clinical trial
HIV-MSM vaccine (n = 66) | HIV-MSM placebo (n = 63) | p* | |
---|---|---|---|
Age, years; mean (±SD) | 37.3 (±10.6) | 40.5 (±10.02) | 0.082 |
Spanish nationality, n (%) | 63 (95.5) | 60 (95.2) | 0.2 |
University education, n (%) | 34 (51.5) | 35 (55.5) | 0.56 |
Partners in the previous 12 months; median (IQR) | 1 (1–3) | 1 (1–5) | 0.8 |
Life-time partners; n, median (IQR) | 50 (20–300) | 100 (45–350) | 0.041* |
Years of sexual activity; median (IQR) | 17 (9–24) | 21 (13–27) | 0.025* |
Condom use, n (%) | 53 (80.3) | 47 (74.6) | 0.4 |
Perianal/genital condylomas at screening, n (%) | 20 (30.3) | 20 (31.7) | 0.86 |
History of condylomas, n (%) | 19 (28.8) | 15 (23.8) | 0.52 |
Duration of HIV; mean months (IQR) | 58 (26–120) | 77 (37–138) | 0.2 |
History of AIDS; n (%) | 19 (28.8) | 21 (33.3) | 0.58 |
CD4 mean nadir; cells/µL, (±SD) | 336 (±227.3) | 334.2 (±193.7) | 0.96 |
CD4 mean; cells/µL (±SD) | 733 (±252.7) | 710.4 (±266.6) | 0.62 |
CD8 mean; cells/µL (±SD) | 999.9 (±463.6) | 992.2 (±374.9) | 0.98 |
VL of HIV log10; copies/mL (±SD) | 3.76 (±4.5) | 3.67 (±4.46) | 0.8 |
VL <50 copies/mL, n (%) | 53 (80.3) | 53 (84.1) | 0.57 |
Virological failure, n (%) | 1 (1.5) | 3 (4.8) | 0.29 |
Median duration of ART; months (IQR) | 42 (17–86) | 43 (17–129) | 0.42 |
Number of lines of ART, median (IQR) | 1 (1–2) | 1 (1–2) | 0.56 |
Syphilis treated, n (%) | 16 (24.2) | 12 (19.1) | 0.47 |
Other STD, n (%) | 11 (16.6) | 12 (19.1) | 0.72 |
Latent tuberculosis treated, n (%) | 5 (7.6) | 10 (15.9) | 0.14 |
HCV, n (%) | 2 (3) | 2 (3.2) | 1 |
HBV, n (%) | 2 (3) | 0 (0) | 0.49 |
Smoking, packets/year, median (IQR) | 0.2 (0–1) | 6.5 (0–18) | 0.008* |
Ex-smoking, n (%) | 10 (15) | 13 (20.6) | 0.0.42 |
Ex-IVDA, n (%) | 1 (1.5) | 0 (0) | 0.42 |
Alcohol (standard units of alcohol; SUA) | 0 (0–1) | 0.4 (0–1.4) | 0.15 |
Variable | HIV-MSM vaccine (n = 66) | HIV-MSM placebo (n = 63) | p* |
---|---|---|---|
PCR of HPV | |||
LR-HPV, n (%) | 39 (59) | 34 (53.9) | 0.63 |
HR-HPV, n (%) | 46 (69.7) | 44 (69.8) | 0.87 |
HR and LR HPV, n (%) | 28 (42.4) | 31 (49.2) | 0.39 |
Number of HR-HPV (IQR) | 1 (0–2) | 2 (0–3) | 0.22 |
Number of LR-HPV (IQR) | 1 (0–2) | 1 (0–2) | 0.94 |
Genotypes, n (%) | |||
HPV6 | 11 (16.6) | 8 (12.6) | 0.55 |
HPV11 | 8 (12.1) | 7 (11.1) | 0.88 |
HPV16 | 15 (22.7) | 15 (23.8) | 0.85 |
HPV16 species | 22 (33.3) | 24 (38.1) | 0.49 |
HPV18 | 4 (6.1) | 5 (7.9) | 0.74 |
HPV18 species | 18 (27.3) | 22 (34.9) | 0.35 |
Cytology, n (%) | |||
Normal | 26 (39.4) | 27 (42.9) | 0.69 |
LSIL | 34 (51.5) | 26 (41.3) | 0.24 |
HSIL | 1 (1.5) | 4 (6.3) | 0.21 |
ASC | 5 (7.6) | 6 (9.5) | 0.69 |
HRA, n (%) | |||
Normal | 33 (0.5) | 29 (46) | 0.65 |
LSIL | 33 (0.5) | 34 (53.9) | 0.65 |
Safety of qHPV vaccine
Adverse events | V1: vaccine vs. placebo N (%) p* | V2: vaccine vs. placebo N (%) p* | V3: vaccine vs. placebo N (%) p* |
---|---|---|---|
Total AE | 36 (54.4) vs. 55 (87.3) 0.0001 | 59 (89.4) vs. 62 (98.4) 0.06 | 44 (66.7) vs. 57 (91.9) 0.0001 |
Injection-site pain | 37 (56.1) vs. 53 (83.6) 0.0001 | 58 (87.8) vs. 62 (98.4) 0.0001 | 45 (67.7) vs. 57 (91.9) 0.0001 |
Local itching | 10 (15.1) vs. 5 (8) 0.13 | 1 (1.5) vs. 1 (1.6) 0.37 | 1 (1.5) vs. 0 0.33 |
Syncope | 2 (3) vs. 0 0.5 | 1 (1.5) vs. 0 0.33 | 1 (1.5) vs. 0 0.33 |
AE leading to treatment discontinuation | 0 vs. 0 | 0 vs. 0 | 0 vs. 0 |
Deaths | 0 vs. 0 | 0 vs. 0 | 0 vs. 0 |
Serious AE | 0 vs. 0 | 0 vs. 0 | 0 vs. 0 |
Grade 3 or 4 abnormalities | 0 vs. 0 | 0 vs. 0 | 0 vs. 0 |
Immunogenicity of qHPV vaccine
Risk factors associated with the presence of HR-HPV genotypes
Bivariate analysis
Factors | HIV-MSM with HR-HPV (n = 117) | HIV-MSM without HR-HPV (n = 43) | p* | RR; (95% CI) |
---|---|---|---|---|
Age; mean years (±SD) | 36.3 (9.7) | 42.1 (10.4) | 0.001 | 0.98; (0.96–0.99) |
Age ≥ 50 years, n (%) | 12 (10.3) | 11 (25.6) | 0.014 | |
University education, n (%) | 68 (58.1) | 19 (44.1) | 0.2 | |
Partners in the previous 12 months; median (IQR) | 1 (1–5) | 1 (0.75–4.25) | 0.24 | |
Life-time partners; median (IQR) | 80 (25–300) | 50 (19–212.5) | 0.38 | |
Time since commencement of sexual activity (years); median (IQR) | 17 (9–24) | 21 (13–27) | 0.036 | 1.35; (1.001–1.811) |
Condom use, n (%) | 96 (82.1) | 29 (67.4) | 0.048 | 1.14; (0.857–1.509) |
% condom use; median (IQR) | 100 (70–100) | 98 (0–100) | 0.066 | |
Perianal/genital warts, n (%) | 31 (26.5) | 16 (37.2) | 0.19 | 1.57; (0.466–1.716) |
History of warts, n (%) | 34 (29.1) | 13 (30.2) | 0.8 | |
Smoking, packets/year; median (IQR) | 1.8 (0–12) | 0.7 (0–16) | 0.8 | |
21 (17.9) | 7 (16.3) | 0.8 | ||
Ex-smoker, n (%) | 1 (0.85) | 0 (0) | 1 | |
Ex-IVDA, n (%) | 0.14 (0–1) | 0 (0–1.3) | 0.66 | |
Duration of HIV; mean (IQR) | 54 (19–118) | 74 (49.2–139.7) | 0.002 | 0.998; (0.995–1.002) |
CD4 mean nadir; cells/µL (± SD) | 345.9 (±217.9) | 323.1 (±164.5) | 0.54 | |
Treatment naïve | 12 (10.3) | 2 (4.6) | 0.35 | 1.33; (0,99–1.77) |
VL of HIV, log10 (±SD) | 3.8 (±4.5) | 3.4 (±4.2) | 0.8 | |
VL <50 copies/mL, n (%) | 90 (76.9) | 39 (90.7) | 0.051 | |
VL ≥200 copies/mL, n (%) | 21 (17.9) | 1 (2.3) | 0.01 | 1.42; (1.172–1.732) |
CD4 mean; cells/µL, (±SD) | 683.7 (±263.6) | 717.3 (±228.3) | 0.46 | |
CD8 mean; cells/µL (±SD) | 984.1 (±407.2) | 996.9 (±402.7) | 0.86 | |
Prior AIDS diagnosis; n (%) | 33 (28.2) | 11 (25.6) | 0.74 | |
Median duration of ART; months (IQR) | 28 (10–95) | 60.5 (31.5–124.5) | 0.08 | 1.002; (0.998–1.005) |
1 (1–2) | 1 (1–2) | 0.59 | ||
Syphilis, n (%) | 28 (23.9) | 7 (16.2) | 0.29 | |
Others STD, n (%) | 22 (18.8) | 7 (16.3) | 0.8 | |
HCV, n (%) | 4 (3.4) | 1 (2.3) | 1 | |
HBV, n (%) | 1 (0.85) | 2 (4.6) | 0.49 |