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  • As the presence of HPV specific antibodies at time


    As the presence of HPV-specific UNC0638 at time of vaccination is related to antibody response to vaccination [28], we evaluated its influence on the antibody responses among HIV+ and HIV− individuals at Months 7 and 18. Despite the small numbers, we observed that HIV+ men with detectable serum HPV antibodies at the time of vaccination, developed stronger antibody responses than the HPV-seronegative men at both time points after vaccination. HIV− men who were HPV- seropositive at Day 1 did not mount significantly higher antibody responses when compared with HPV-seronegative individuals. In contrast to the serum, oral antibody levels were not significantly different by baseline HPV sero-status, except for higher oral HPV-18 antibodies at Month 18 in HPV-seropositive HIV+ men when compared with the HPV-seronegative men. The observed loss in oral antibody detectability may be related to assay sensitivity issues, as even in serum, only 80% of individuals had detectable responses to vaccination. Loss of detectability of HPV-18 antibody responses has been observed in previous studies [29], despite the lack of breakthrough infections, suggesting that new assays with higher sensitivity are warranted for use at mucosal sites, where levels are much lower. Furthermore, different methods of collection were used in the two cohorts studied. To minimize influence of the method of collection and adjust for differences in oral collection volumes, oral antibody data were normalized by total IgG levels determined in each sample. The role of antibody avidity has been demonstrated in vaccine protection against other infections [30] and it is likely to play an important role in protecting against HPV infection. HPV-16 and HPV-18 avidity was slightly lower among HIV+ compared with HIV− men at Month 7. Of significance, lower HPV-16 avidity was observed among individuals without viral suppression. In contrast to serum antibody levels, avidity levels did not appear to be influenced by Day 1 HPV sero-status. Overall, these findings suggest that vaccine induced affinity maturation in HIV-infected and uninfected mid-adult aged males is similar, with some influence of plasma HIV-1 RNA in HPV-16 avidity levels. Weak correlations were observed between avidity and antibody levels following HPV vaccination suggesting these measures are independent as they relate to different aspects of the B cell response. Correlations were weak between CD4 levels and viral load and antibody measurements. This could be due to the fact that most of the individuals were virally suppressed with relatively high CD4 T cell counts. To address the role of plasma HIV-1 RNA and CD4 depletion extent in HPV-specific antibody measurements, larger studies in populations with a wider range of clinical parameters are needed. In conclusion, HIV− and HIV+ men developed comparable plateau antibody levels following UNC0638 qHPV vaccination, although lower peak antibody levels were observed among HIV+ men. HPV seropositivity at baseline played a critical role in antibody levels achieved after vaccination among the HIV+ men. The comparable plateau antibody responses and high antibody avidity levels among the HIV+ and HIV− groups are suggestive that long-term immunogenicity and protection may be observed. Although other factors need to be taken into account, overall, these findings strongly support the consideration of vaccinating both HIV− and HIV+ mid-adult aged men for the prevention of infection and cancer at the oral cavity and at other HPV-susceptible anatomic sites.
    Introduction It was estimated that 36.9 million people were living with HIV in 2017 and there were 1.8 million new infections [1]. Antiretroviral (ARV) drugs are used to treat and prevent HIV infection. Standard antiretroviral therapy (ART) currently consists of a triple combination of drugs from at least two drug classes. ART is able to suppress HIV replication resulting in immune restoration and this has significantly reduced the number of AIDS-related deaths [2]. Infectious HIV-1 viruses are generated by the proteolytic activity of the viral protease (PR) enzyme through the specific cleavage of Gag and Gag/Pol precursors. The absence of protease activity leads to defective viral particles and reduced infectivity [3,4] and inactivation of HIV-1 PR activity results in the lack of infectious viruses [5,6]. Over the last 15 years, multiple HIV-1 protease inhibitors (PI) have been developed and approved for the treatment of HIV-infection. Today, HIV PIs are primarily co-administration with low-dose ritonavir (RTV) or cobicistat (COBI) to increases their bioavailability [7,8].