CROI 2016 Abstract eBook

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Oral Abstracts

Methods: Incident malignancies in START were categorized into any type, infection-related and infection-unrelated cancer. Infection-related cancer was defined as cancer driven by any infectious agent. Independent factors associated with each cancer category were assessed by multivariable Cox models. To investigate why immediate ART initiation reduced cancer risk we used sequential adjustment for baseline covariates, cancer risk factors and HIV-specific variables to fit Cox models with a study arm indicator. Results: There were 14 cancers among persons randomized to the immediate ART arm (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated) (Hazard Ratios [HR]; 95% CI; of immediate vs deferred ART initiation were 0.26; 0.11-0.64; for infection-related and 0.49; 0.21-1.15; for infection-unrelated cancer). In adjusted analyses with both treatment groups combined, older age (adjusted HR; 95% CI: 1.85; 1.44-2.39 per 10y), white race (2.80; 1.13-6.92 vs black) and HIV RNA (1.57; 1.08-2.28 per 1log higher) were linked to risk of any type cancer. Independent predictors of infection-related cancer were older age (1.42; 0.99-2.02 per 10y), higher BMI (1.08; 1.01-1.16 per Kg/m 2 ), low income region (0.32, 0.14-0.74 for high vs low income) and HIV RNA (2.32; 1.35-3.98 per 1log higher). Older age was the only independent predictor of infection-unrelated cancer (2.58; 1.75-3.81 per 10y). Adjustment for latest HIV RNA level, but not for CD4 count or cancer risk factors, attenuated the effect of immediate ART on any type of cancer and infection-unrelated cancer (Figure). Adjustment for latest HIV RNA level had little impact on the protective effect of immediate ART on infection-related cancer. Conclusions: Immediate ART initiation significantly reduces the risk of infection-related cancer. Though limited by small sample size, this benefit doesn’t appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.

Oral Abstracts

161 ACTG A5298: A Phase 3 Trial of the Quadrivalent HPV Vaccine in Older HIV+ Adults Timothy J. Wilkin 1 ; Huichao Chen 2 ; Michelle Cespedes 3 ; Pawel Paczuski 2 ; Catherine Godfrey 4 ; Elizabeth Chiao 5 ; Amneris Luque 6 ; JenniferY.Webster-Cyriaque 7 ; Barbara Bastow 8 ; Ross Cranston 9 ; for the ACTG A5298 ProtocolTeam 1 Weill Cornell Med Coll, New York, NY, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Icahn Sch of Med at Mount Sinai, New York, NY, USA; 4 DAIDS, NIAID, NIH, Rockville, MD, USA; 5 Baylor Coll of Med, Houston, TX, USA; 6 Univ of Rochester Med Cntr, Rochester, NY, USA; 7 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 8 Social & Scientific Systems, Inc., Silver Spring, MD, USA; 9 Univ of Pittsburgh Sch of Med, Pittsburgh, PA, USA Background: HIV-infected individuals are at increased risk for human papillomavirus (HPV)-associated cancers. Quadrivalent HPV vaccine (qHPV) licensure studies were conducted in HIV-uninfected populations ≤26 yrs old with low exposure to HPV; qHPV is safe and immunogenic in HIV infected adults. Methods: Phase 3, randomized, double-blind, placebo-controlled trial of qHPV in HIV-infected adults age 27 years and older with no previous HPV-associated cancer. Men were required to have a recent history of receptive anal sex. Participants had baseline assessments for anal and oral HPV (2 timepoints), anal cytology, and high resolution anoscopy (HRA). Participants received qHPV (or placebo) at entry, weeks 8 and 24. Anal HPV, cytology and oral HPV testing were obtained every 6 months. Treatment of HSIL and follow- up HRA was according to local standard of care. The primary endpoint was persistent anal HPV infection (or single detection at the final visit) in those without the infection at baseline. We hypothesized a 65% reduction with qHPV. The study was conducted at 23 US sites and 1 Brazil site. 99.9% confidence intervals are presented since the data are from a pre-specified DSMB review employing a Haybittle-Peto boundary of 0.001. Results: 575 participants were enrolled (472 (82%) male, 103 (18%) women), 262 (46%) were white/non-Hispanic, 179 (31%) were black/non-Hispanic, 117 (20%) were Hispanic. Median age was 47 years [IQR 41-53], median CD4 602/µL [IQR 436-767], 83% had HIV RNA <50 copies/mL, 558 (97%) completed vaccination. With 2.1 years median follow-up, persistent anal HPV infection with qHPV types was 30% lower than hypothesized. Conditional power to show a significant difference in the primary endpoint was 7% should the study complete with similar event rates. Conditional power for detecting a difference in anal HSIL was <1%. The DSMB recommended stopping the trial due to futility. The qHPV was safe and well tolerated. Conclusions: This study does not support HPV vaccination in older HIV-infected adults for prevention of new anal HPV infections or to improve HSIL treatment outcomes, but does suggest a trend for protection against oral infection. The role of qHPV for prevention of oral HPV infections should be further investigated. These results underscore the need for HPV vaccination prior to HPV exposure.

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CROI 2016