1. HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Slideset on: Duerr A, Paramsothy P, Jamieson DJ, et al. Effect of HIV infection on atypical squamous cells of undetermined significance. Clin Infect Dis. 2006;42:855-861.

2. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861. Background and Rationale  Atypical squamous cells of undetermined significance (ASCUS) etiology and outcome uncertain  Management guidelines vary according to patient’s HIV status, likelihood of developing high-grade squamous intraepithelial lesions (SILs)  Unknown whether current guidelines for HIV-infected women optimal, given uncertain significance between ASCUS, cervical intraepithelial neoplasia  Current study compared prevalence, characteristics, and risks associated with ASCUS between HIV-infected and HIV-uninfected women

3. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861. Summary of Study Design  HIV-infected and at-risk, HIV-uninfected women enrolled in 4 US cities between April 1993 and January 1995  Pap tests, gynecologic exams, Gram stains, HPV testing, and HIV-1 testing performed at each semiannual visit –2 sites referred for colposcopy if Pap test showed SILs or 2 consecutive Pap tests showed ASCUS; other site routinely performed colposcopy at each visit –For HIV-infected women, HIV-1 RNA, CD4+ cell count, and self-reported antiretroviral use determined  ASCUS cumulative incidence estimated using product- limit survival estimator; median follow-up: 4.4 years

4. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861. Baseline Characteristics  N = 1199; 795 HIV-infected, 404 at-risk, HIV-uninfected  Compared with HIV-uninfected women, HIV-infected women: –More likely to be black –Less likely to have completed high school –More likely to use condoms within 6 months prior to enrollment –Less likely to use crack within 6 months prior to enrollment –Less likely to have > 1 male sexual partner within 6 months prior to enrollment

5. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861.  Pap test data for 10 semiannual visits (up to 4.7 years) included in analysis; included 8185 Pap tests  ASCUS characteristics generally comparable between HIV-infected and HIV-uninfected women  HIV-infected women more likely than HIV-negative women to be coinfected with HPV (58% vs 24%; P <.01)  HIV-infected women more likely to have high-risk HPV infection (23% vs 14%; P <.01)  HIV-infected women more likely to have Candida vaginal infection (37% vs 28%; P <.01) Main Findings

6. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861.  Factors significantly associated with ASCUS in all women: –HIV infection –Cumulative incidence in women with normal Pap at enrollment, 78% in HIV-infected women vs 38% in HIV-uninfected women (P <.01) –Presence of cervical ectopy, HPV risk type, black race, Pap results at last visit  CD4+ cell count < 200 cells/mm 3 significantly associated with ASCUS in HIV-infected women Risk Factors for Developing ASCUS

7. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861. Risk Factors for ASCUS, Progression of ASCUS to SILs Characteristic Adjusted HR (95% CI) for ASCUS All Women (n = 701) HIV-Infected Women (n = 426) All Women (n = 196) HIV-Infected Women (n = 148) HIV infected1.8 (1.4-2.3)--2.4 (1.2-4.9)-- CD4+ cell count < 200 cells/mm 3 --1.9 (1.2-2.9)--1.7 (0.8-3.6) HPV risk type  High/intermediate3.2 (2.4-4.3)3.1 (2.2-4.3)2.4 (1.2-4.6)2.4 (1.1-5.2)  Low/untypeable1.6 (1.2-2.1)1.8 (1.3-2.5)1.6 (0.7-3.5)1.6 (0.6-3.4) Positive Candida culture1.3 (1.0-1.7)1.4 (1.1-1.8)--

8. clinicaloptions.com/hiv HIV Infection Increases Risk of ASCUS and Subsequent Development of SILs Duerr A, et al. Clin Infect Dis. 2006;42:855-861. Key Conclusions  HIV-infected women more likely to develop ASCUS based on Pap results than HIV-uninfected women –HIV-infected women with low CD4+ cell count particularly at risk  HIV-infected women with ASCUS more likely to progress to develop SILs than HIV-uninfected women –Those with low CD4+ cell count particularly at risk  Findings indicate that current guidelines recommending colposcopy for HIV-infected women with ASCUS appropriate