A total of 3014 participants were enrolled in the trials, of whom 2300 (76.3%) were vaccinees (and 714 [23.7%] placebo recipients), with 2176 (94.6%) of vaccinees having EOS testing data available (11 [0.5%] had EOS testing pending and 92 [4.0%] did not have EOS testing done, the majority due to loss to follow-up), with 16 excluded from the analysis due to becoming HIV-1 infected and 5 for vaccine administration issues (eg, wrong product administered, product viability uncertain) ().
There were 2176 non-HIV infected vaccine recipients with HIV test results available from the EOS testing algorithm at the time of data analysis. Although the algorithm specified that three different EIA kits be run, 182 (8.4%) participants from the earliest trials were missing kit results other than HIV 1/2 (rDNA) results from one (n=171) or two (n=11) kits.
The majority of participants (82%) in the analysis were from the US (). Among US participants, 57% were men, 70% were white, and the median age was 29 years. African participants had a slightly younger median age of 25, and 49% were male. Participants from South America and the Caribbean were drawn from ethnic/racial groups representative of their respective countries and had a median age of 27, with 57% being male.
VISP occurred in 908 of the 2176 participants (41.7%; 95% confidence interval [CI], 39.6%–43.8%, ). VISP rates varied greatly by type of HIV vaccine administered. For viral vectored vaccines, alphavirus replicon products containing the gag antigen alone were found to have the lowest VISP (1.0%; [95% CI, 0.0%–5.2%]). In contrast, Ad5 products containing envelope antigens given alone or as a boost to a DNA prime were found to have the highest VISP (92.7%; [95% CI, 89.8%–95.0%]). Within the DNA only product category VISP occurred in 18.9% (95% CI, 13.2%–25.7%) of participants receiving a VRC DNA product, whereas it occurred in only 1% (95% CI, 0.3%–2.6%) of participants receiving other DNA vaccines. For poxvirus products given alone or as a boost to a DNA or poxvirus prime, 53.4% (95% CI, 49.2%–57.7%) of recipients had VISP. This was similar to the 48.6% (95% CI, 41.9%–55.4%) occurrence for canarypox given in combination with a protein or peptide product. All 70 recipients of a gp140 vaccine had VISP, whereas recipients of other protein and peptide products given alone or as a DNA boost had a VISP rate of 0.5% (95% CI, 0.0%–2.6%).
Vaccine Induced Seropositivity/Reactivity Rates by Type of HIV-1 Vaccine and EIA Kit
The HIV 1/2 (rDNA) kit was selected for inclusion in the EOS testing algorithm since it is a commonly used diagnostic kit in the US and has been noted to be particularly sensitive to detecting vaccine induced HIV antibodies. Only 17 (1.9%) of 908 participants with VISP did not test reactive using the HIV 1/2 (rDNA) kit (). Within product categories VISP occurred more frequently with the HIV 1/2 (rDNA) kit than the other kits (except for alphavirus replicon category, wherein a single participant was found to have VISP detected with only the HIV 1/2 Peptide kit. The gp140 product was unique in that 94.3% of recipients were reactive on all three kits. The other kits varied on their rates of reactivity, especially for viral-vectored vaccines (). Although kit data are summarized for all participants with a kit result, data are similar when limiting comparisons to participants tested with the same three kits.
Almost all of VISP was associated with vaccines that contain env, either alone or in combination with other HIV-1 antigens (). Only 8 participants with VISP received a vaccine not containing env: 5 received Ad5 (gag, pol, nef inserts) and tested reactive using the HIV 1/2 (rDNA) kit; 2 received gag DNA and tested reactive using the HIV 1/2 (rDNA) kit; and 1 received alphavirus replicon (gag insert) and tested reactive using a HIV 1/2 Peptide kit.
Vaccine Induced Seropositivity/Reactivity Rates and Western Blot Resultsa by Vaccine Insert HIV-1 Genesb
Within the vaccine sub-product categories, no gender or age differences in VISP were observed within geographical regions or for regions combined. One racial difference was observed for US participants receiving VRC Ad5 alone (93.2% white vs 50.0% black; P = .01; no participants in Africa received this product), although this is based on only 6 black individuals and was not observed for VRC DNA prime and Ad5 boost. This analysis is not adjusted for multiple testing.
For those testing reactive on one or more EIA kits, all except 7 had a Western blot result (, ). Overall, 10.2% (n=92) had a positive Western blot, 65.7% (n=592) tested indeterminate, and 24.1% (n=217) tested negative; however, the distribution of results varied by product. For DNA and fowlpox vaccines, ≥ 50.0% had negative Western blots. The env-containing Ad5 vaccine given alone or as a DNA vaccine boost had the highest proportion of positive results (25.4% and 13.6%, respectively). Poxvirus regimens had higher percentages of indeterminate results (50.0%–97.3%) and positive results <10%.
Western Blot Results for Participants with Vaccine Induced Seropositivity/Reactivity by Vaccine Product Category
For those with a positive Western blot result, all but 1 had a positive gp160 band (11 had missing data). For gag bands, all but 1 was positive for p24, and 44 (53.7%) were positive for p55 (30 received an Ad5 product and 14 a poxvirus vectored vaccine; 10 had missing data). For pol bands, p51 was positive for only 6 participants (4 received an Ad5 vaccine and 2 received poxvirus; 10 had missing data) and no one had a positive p31 band (11 had missing data). For those with an indeterminate Western blot, p24 was positive for 91.1% who received a poxvirus vectored vaccine regimen, and 17.8% who received other vaccines (3 had missing data). Data on other bands were not consistently available for participants with an indeterminate Western blot who received a poxvirus vectored vaccine. For other products, only the gp160 band had a substantial number of positives, particularly for a gp140 vaccine, 83.9% of which were positive.