Cases and controls in both cohorts were demographically similar (). MACS cohort: we obtained baseline Ad5 titers on 214 cases and 423 matched controls who did not become infected during an equivalent observation period. Ad5 titers > 18 were found in 246 persons near the time of acquisition or censoring. The rates of Ad5 seropositivity differed by no more than 2% between cases and controls (). The odds ratio for incident HIV infection among Ad5-seropositives vs. Ad5-seronegatives was 1.1, which was not statistically significant (95% CI = 0.8 – 1.5, p = 0.57).
Because participants from the MACS cohort were not matched on circumcision status, a factor associated with HIV acquisition in Step study vaccinees, we sought to evaluate the effect of circumcision on the relationship between Ad5 serostatus and risk of HIV infection. Circumcision status was available for 106 cases and 317 controls. Eighty-eight % (93/106) of cases and 97% (306/317) of controls were circumcised (p = 0.001). Circumcision status was not associated with Ad5 serostatus; 42% (10/24) of uncircumcised men had detectable Ad5 nAb titers, versus 37% (148/399) of circumcised men (p = 0.63). These observations indicate that the lack of association between Ad5 and HIV acquisition is unlikely to be attributable to confounding or competing effects of circumcision and Ad5 exposure.
CCR5Δ32 deletion genotype information was available on 359 persons; 64 individuals were heterozygous for CCR5Δ32, including 41 Ad5 seronegatives and 23 Ad5 seropositives. 8 individuals were CCR5Δ32 homozygous, including 3 Ad5 seronegatives and 5 Ad5 seropositives. There was no significant association between Ad5 serostatus and presence of the CCR5Δ32 deletion, in either the heterozygous or homozygous state (RR = 0.87, p = 0.48 and RR = 1.52, p = 0.14, respectively). In separate adjusted conditional logistic regressions, including a) circumcision status and b) presence of either one or two copies of the CCR5Δ32 deletion, the odds of being a case in the MACS cohort were not associated with Ad5 detection (p = 0.14 and p = 0.45, respectively). When these analyses were repeated while excluding the 8 individuals homozygous for the CCR5Δ32 deletion, again there was no association between HIV-1 case status and presence or absence of Ad5 neutralizing antibody titers > 18 (p = 0.45)
HPTN 039 cohort: Of 254 original participants, 252 participants were included in analysis. Two controls were excluded as there was not a valid titer for Ad5 in the corresponding case, and three cases only had one control with valid Ad5 serostatus. Thus the analysis was performed with 85 cases and 167 controls (). The 31 cases and matching controls from Zambia were women while the remaining participants were men. In this cohort, the odds ratio for incident HIV infection among Ad5-seropositives vs. Ad5-seronegatives was 1.0 (95% CI = 0.4 – 2.3, p = 0.99). Inclusion of circumcision status in the regression model for HPTN039 also did not alter the significance of Ad5 detection versus the case status (OR = 1.0, 95% CI = 0.4 – 2.5, p = 0.99). Information on CCR5Δ32 genotype was not available in this cohort. In neither MACS nor HPTN039 was there an apparent relationship between Ad5 titer and HIV acquisition rate ().
Ad5 neutralizing antibody titers and HIV acquisition