Jeanne M. Marrazzo, MD, MPH; Carlos del Rio, MD; David R. Holtgrave, PhD; Myron S. Cohen, MD; Seth C. Kalichman, PhD; Kenneth H. Mayer, MD; Julio S. G. Montaner, MD; Darrell P. Wheeler, PhD, MPH; Robert M. Grant, MD, MPH; Beatriz Grinsztejn, MD, PhD; N. Kumarasamy, MD, PhD; Steven Shoptaw, PhD; Rochelle P. Walensky, MD, MPH; François Dabis, MD, PhD; Jeremy Sugarman, MD, MPH; Constance A. Benson, MD HIV Prevention in Clinical Care Settings: 2014 Recommendations of the International IAS-USA-Society Panel Marrazzo et al, JAMA, 2014.

Slide 2 of 37 HIV Prevention in Clinical Care Settings: 2014 Recommendations of the International Antiviral Society-USA Panel Free web access to the paper at jama.com

Slide 3 of 37 IAS-USA HIV Prevention Recommendations: Goal Worldwide, ~2.3 million new HIV infections in 2012 ─ In US, ~50,000 new HIV infections each year—largely unchanged since the 1990s Integrated biomedical and behavioral HIV prevention tools and ART for treatment offer chance to curb the HIV epidemic Clinicians play a crucial role in implementing combination HIV prevention interventions These recommendations seek to consolidate best practices for clinicians across a range of HIV prevention issues Marrazzo et al, JAMA, 2014.

Slide 4 of 37 IAS-USA HIV Prevention Recommendations: Process In 2013, international panel of HIV experts assembled by IAS-USA to develop evidence-based recommendations that integrate biomedical and behavioral interventions for HIV prevention in the clinical care setting IAS-USA, a 501(c)(3) not for profit organization that sponsors CME for physicians and medical practitioners involved in the care of people with HIV, HCV, or other viral infections, sponsored and provided all funding for the recommendations Volunteer panel members worked in teams to review and summarize scientific evidence and propose recommendations Final recommendations approved by panel consensus; ratings assigned based on strength of recommendation and quality of evidence

Slide 5 of 37 IAS-USA HIV Prevention Recommendations: Panel Members Myron S. Cohen, MD University of North Carolina Seth C. Kalichman, PhD University of Connecticut Kenneth H. Mayer, MD Harvard Medical School Julio S. G. Montaner, MD University of British Columbia Darrell P. Wheeler, PhD, MPH Loyola University Chicago Robert M. Grant, MD, MPH University of California San Francisco Beatriz Grinsztejn, MD, PhD Evandro Chagas Clinical Research Institute (IPEC)–FIOCRUZ N. Kumarasamy, MD, PhD YR Gaitonde Centre for AIDS Research and Education Steven Shoptaw, PhD University of California Los Angeles Rochelle P. Walensky, MD, MPH Massachusetts General Hospital François Dabis, MD, PhD Université de Bordeaux Jeremy Sugarman, MD, MPH The Johns Hopkins University Constance A. Benson, MD University of California San Diego Margaret A. Fischl, MD University of Miami Cochairs Jeanne M. Marrazzo, MD, MPH University of Washington Carlos del Rio, MD Emory University David R. Holtgrave, PhD The Johns Hopkins Bloomberg School of Public Health

Slide 6 of 37 IAS-USA HIV Prevention Recommendations: Rating System Strength of Recommendation AStrong support for the recommendation BModerate support for the recommendation CLimited support for the recommendation Quality of Evidence Ia Evidence from 1 or more randomized controlled clinical trials published in the peer-reviewed literature Ib Evidence from 1 or more randomized controlled clinical trials presented in abstract form at peer-reviewed scientific meetings IIa Evidence from nonrandomized clinical trials or cohort or case-control studies published in the peer-reviewed literature IIb Evidence from nonrandomized clinical trials or cohort or case-control studies presented in abstract form at peer-reviewed scientific meetings IIIRecommendation based on the panel’s analysis of the accumulated available evidence Adapted in part from Canadian Task Force on the Periodic Health Examination, Can Med Assoc J, 1979

Slide 7 of 37 IAS-USA HIV Prevention Recommendations: Sections HIV Testing and Knowledge of Serostatus Prevention Measures for HIV-Infected Individuals Prevention Measures for HIV-Uninfected Individuals Prevention Issues Relevant to All Persons With or At Risk for HIV Infection Marrazzo et al, JAMA, 2014.

HIV Testing and Knowledge of Serostatus Marrazzo et al, JAMA, 2014.

Slide 9 of 37 HIV Testing and Knowledge of Serostatus Recommendations All adults and adolescents should be offered HIV testing at least once. Rating: AIII ─To direct the need for additional testing, clinicians should periodically assess HIV-related risks, including sexual and drug-use activities, in all adults and adolescents. ─Persons at higher risk (those engaging in risk behaviors or residing in areas of or testing at venues with high seroprevalence) should be tested more frequently, at intervals appropriate to the individual’s situation. Marrazzo et al, JAMA, 2014.

Slide 10 of 37 HIV Testing and Knowledge of Serostatus (cont’d) Recommendations All should be informed prior to undergoing HIV testing; however, pretest counseling should be sufficient only to meet the individual’s needs and comply with local regulations. The right to refuse testing must be honored, but clinicians should ensure that refusals are informed decisions. Rating: AIII As circumstances warrant and depending on test used, at-risk persons who test HIV-seronegative should receive information about the possibility of a false-negative test result during the window period prior to appearance of detectable antibody, and should be encouraged to obtain repeat testing at an appropriate time. Rating: AIIa Marrazzo et al, JAMA, 2014.

Slide 11 of 37 HIV Testing and Knowledge of Serostatus (cont’d) Recommendations Tests with the best performance (sensitivity/specificity) should be used. Rating: AIIa Rapid testing should be prioritized for persons less likely to return for their results. Rating: AIIa Couples testing should be accommodated and encouraged. Rating: Ala Self-testing and home testing should be considered for those who have recurrent risk, have difficulties with testing in clinical settings, or both. Rating: BIII Marrazzo et al, JAMA, 2014.

Prevention Measures for HIV-Infected Individuals Marrazzo et al, JAMA, 2014.

Slide 13 of 37 Antiretroviral Therapy Recommendations Clinicians should provide education about personal health benefits of ART and public benefits of prevention of transmission, and assess patients’ readiness to initiate and adhere to long-term ART. Rating: AIII ART should be offered upon detection of HIV infection. Rating: A1a Strategies for adherence support should be implemented and tailored to individual patient needs or the setting. Rating: AIa Clinicians should be alert to the nonspecific presentation of acute HIV infection and urgently pursue specific diagnostic testing (plasma HIV viral load) if suspected. Rating: AIIa Marrazzo et al, JAMA, 2014.

Slide 14 of 37 Counseling on Risk Reduction, Disclosure of HIV Serostatus, and Partner Notification Recommendations Regular assessment of sexual and substance use practices should be performed in HIV-infected persons to direct individualized risk- reduction counseling, which should be delivered in combination with STI screening, condom provision, and harm reduction services for people who inject drugs, and integrated with strategies to maintain adherence. Rating: AIII Assistance should be provided for patient- or clinician-based notification of sex and injection drug use partners to facilitate the patient’s testing and linkage to care, as well as efforts to disclose HIV infection to relevant partners and other key persons. Rating: AIII Marrazzo et al, JAMA, 2014.

Slide 15 of 37 Needle Exchange and Other Harm Reduction Interventions Recommendations Simultaneous access to ART, needle and syringe exchange programs, supervised injection sites, medicalized heroin and medically-assisted therapy (which includes opioid-substitution therapy) should be provided to HIV-infected people who inject drugs. Rating: AIa for each element; AIII for the combination For individuals who use substances in ways other than injection, ART with adherence support and behavioral counseling should be provided. Rating: AIIa Marrazzo et al, JAMA, 2014.

Slide 16 of 37 Strategies for Promoting Movement Through the Continuum of HIV Care Recommendations Linkage to HIV care for HIV-infected individuals is an essential component of expanded HIV testing and should be actively facilitated as soon as possible following a new diagnosis of HIV. Rating: AIa Strengths-based case management interventions, in which patients identify and use personal strengths, should be used to facilitate linkage to and retention in HIV care. Rating: AIa Additional patient support services are recommended, including patient health navigation, community and peer outreach, provision of culturally appropriate print media, verbal messages promoting health care utilization and retention from clinic staff, and youth-focused case management and support. Rating: AIIa Marrazzo et al, JAMA, 2014.

Slide 17 of 37 Risk Assessment and Risk Reduction for HIV Infection Recommendations A specific risk assessment covering recent months should be conducted to determine the sexual and substance use practices that should be the focus of risk reduction counseling and appropriate risk reduction services should be offered. Rating: AIa For people at high risk for HIV infection who test HIV- seronegative, risk-reduction interventions or services are warranted, especially for individuals and couples who seek repeat HIV testing to monitor seroconversion. Rating: AIa Marrazzo et al, JAMA, 2014.

Prevention Measures for HIV-Uninfected Individuals Marrazzo et al, JAMA, 2014.

Slide 19 of 37 Efficacy of Biomedical Interventions to Prevent HIV Acquisition: Summary of the Evidence from Randomized Clinical Trials Modified from Ambitious Treatment Targets: Writing the Final Chapter of the AIDS Epidemic, UNAIDS, 2014.

Slide 20 of 37 Preexposure Prophylaxis (PrEP) Recommendations Daily FTC/TDF as PrEP should be offered to ─Persons at high risk for HIV based on background incidence (> 2%) or recent diagnosis of incident STIs, especially syphilis, gonorrhea, or chlamydia. Rating: AIa ─Individuals who have used postexposure prophylaxis (PEP) more than twice in the past year. Rating: AIIa ─People who inject drugs and who share injection equipment, inject 1 or more times a day, or inject cocaine or methamphetamines. Rating: AIa Marrazzo et al, JAMA, 2014.

Slide 21 of 37 Preexposure Prophylaxis (cont’d) Recommendations PrEP should be part of an integrated risk-reduction strategy, so its use may become unnecessary if a person’s behavior changed. Thus, clinicians should regularly assess their patients' risk and consider discontinuing PrEP if the sexual and partnering practices or injection drug use behaviors that involved exposure to HIV change. Rating: AIII HIV-infected persons should be asked about the HIV serostatus of their sexual partners, and PrEP should be discussed if they have regular contact with HIV-uninfected partners. Partners whose HIV serostatus is unknown should undergo counseling and testing. Considerations should include whether the infected partner’s viral load is suppressed on ART, access to care for the uninfected partner, and coverage of associated costs. Rating: AIIb Marrazzo et al, JAMA, 2014.

Slide 22 of 37 Preexposure Prophylaxis (cont’d) Recommendations HIV testing should be performed before starting PrEP, ideally with a sensitive, combination antigen-antibody assay capable of detecting acute or early infection (a fourth-generation assay), and regularly (monthly to quarterly depending on individual risk) thereafter. Screening for clinical symptoms that may signal acute infection should be performed. In suspected cases of acute HIV infection, plasma HIV viral load should be determined immediately and PrEP should be deferred until acute infection is ruled out. Rating: Ala Persons to be given TDF-based PrEP should have a creatinine clearance rate of at least 60 mL/min. Data are not available to inform a recommendation for PrEP for persons with a creatinine clearance rate of less than 60 mL/min. Rating: AIa Immunity to HBV should be ensured for all persons initiating TDF-based PrEP. Rating: AIIa Marrazzo et al, JAMA, 2014.

Slide 23 of 37 Postexposure Prophylaxis (PEP) Recommendations PEP should be offered to all persons who have sustained a mucosal or parenteral exposure to HIV from a known infected source as urgently as possible and, at most, within 72 hours after exposure. Rating: AIIb The PEP regimen should consist of the USPHS preferred regimen, which is currently FTC/TDF and raltegravir. Rating: BIIb Women who receive PEP should be offered emergency contraception to prevent pregnancy. Rating: BIIb Persons who receive PEP should be rescreened with a fourth-generation HIV antigen and antibody test 3 months after completion of the regimen. Rating: BIIb Marrazzo et al, JAMA, 2014.

Slide 24 of 37 Voluntary Medical Male Circumcision Recommendations Voluntary medical male circumcision should be recommended to sexually active heterosexual males for the purpose of HIV prevention, especially in areas with high background HIV prevalence. Rating: AIa Voluntary medical male circumcision should be discussed with MSM who engage in primarily insertive anal sex, particularly in settings of high HIV prevalence. Rating: BIIb Parents and guardians should be informed of the preventive benefits of male infant circumcision. Rating: BIIb Marrazzo et al, JAMA, 2014.

Prevention Measures for All Individuals With or at Risk for HIV Infection Marrazzo et al, JAMA, 2014.

Slide 26 of 37 Screening and Treatment for STIs Recommendations: Routine, periodic screening for common STIs at anatomic sites based on sexual history should be performed. Rating: BIIa HIV-infected persons should be tested for HCV at entry to care and assessed at regular intervals for related risks, including higher-risk sexual practices. Rating: BIIa Quadrivalent HPV vaccination should be offered to all HIV-infected persons who fulfill the Advisory Committee for Immunization Practices (ACIP) criteria for its administration. Rating: AIIa Marrazzo et al, JAMA, 2014.

Slide 27 of 37 Screening and Treatment for STIs (cont’d) Recommendations Immunity to HBV should be ensured for all HIV-infected persons in care who have not already been infected with HBV. Rating: AIIa Routine screening for HSV-2 infection should be considered for HIV-infected persons who do not know their HSV-2 serostatus and wish to consider suppressive antiviral therapy to prevent transmission of HSV-2. Rating: CIa Marrazzo et al, JAMA, 2014.

Slide 28 of 37 Reproductive Health Care/ Hormonal Contraception Recommendation Current data are not sufficiently conclusive to restrict use of any HC method, and women using progestin-only injectable contraception should be advised to also always use condoms and other HIV preventive measures as feasible. In the interim, HIV-infected women should be counseled with regard to the availability of a range of options for family planning, including HC. Rating: BIIa Marrazzo et al, JAMA, 2014.

Slide 29 of 37 Summary After 30 years, an AIDS-free generation could be a reality Clinicians’ efforts are needed to: ─ Offer all adults and adolescents HIV testing For all persons with, or at risk for, HIV: ─ Regularly assess substance use and sexual risk practices ─ Offer ART and adherence support at diagnosis of HIV; PrEP and adherence support to those at risk ─ Have a high index of suspicion for nonspecific presentation of symptomatic acute HIV infection ─ Emphasize and support linkage to care ─ Facilitate individualized risk-reduction counseling ─ Conduct regular STI screening Marrazzo et al, JAMA, 2014.

Trends in Annual Age-Adjusted* Rate of Death Due to HIV Infection, United States, 1987−2010 Note: For comparison with data for 1999 and later years, data for 1987−1998 were modified to account for ICD-10 rules instead of ICD-9 rules. *Standard: age distribution of 2000 US population

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Slide 35 of 53 Source: CDC, 2013 and Holtgrave et al, 2012 HIV Continuum of Care 28.6% virologically suppressed General population: 9.2% engaging in risk behaviors HIV-positive: 1,144,500 Diagnosed with HIV: 963,600 Diagnosed with HIV in 2011: 79.8% linked to care Diagnosed with HIV as of 2010: 50.9% retained in care Diagnosed with HIV as of 2010: 327,485 with viral load <200 copies/ml ~50K new infections per year

Slide 36 of 37 HIV Continuum of Care Source: CDC, Approx 1.1 million with HIV in US

The Need for HIV Prevention: Continued HIV Risk in the US Estimated new HIV infections in the United States for the most affected subpopulations, CDC. HIV in the United States: Yr Diagnoses (%) Male-to-male sexual contact Heterosexual contact IDU Male-to-male sexual contact and IDU Other

Rationale for Routine HIV Screening: Initial CD4 Cell Count (NA-ACCORD) Althoff KN, et al. Clin Infect Dis. 2010;50:

Rationale for Routine HIV Screening: Initial CD4 and Response to HAART Palella FJ, et al CROI. Abstract 983. Median CD4+ cell count after Starting HAART (by baseline CD4+ category) > < 50

Rationale for Routine HIV Screening: Initial CD4 and Response to HAART Palella FJ, et al CROI. Abstract 983. Median CD4+ cell count after Starting HAART (by baseline CD4+ category) > < 50

Earlier Diagnosis Has Benefits: Ignorance is Not Bliss Marks et al. AIDS, 2006 ~21% unaware ~79% aware Transmission 54-70% 30-46% Living with HIV: 1.1M New infections Marks et al. AIDS, 2006

Slide 42 of 44 IAS  USA Antiretroviral Guidelines 1996 – 2014 Günthard et al, JAMA, 2014.