New Options for HIV Prevention:
The Role of Antiretrovirals

This program is supported by an educational grant from
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

About These Slides
 Users are encouraged to use the...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Program Director and Core Faculty
Jeanne Marrazzo, M...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Other Faculty Who Contributed to This
Program
Laura ...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Other Faculty Who Contributed to This
Program
Kather...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Other Faculty Who Contributed to This
Program
Anne R...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Faculty Disclosures
Jared M. Baeten, MD, PhD; Susan ...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

The Need for HIV Prevention:
Continued HIV Risk in t...
Treatment of HIV-Infected Persons
for Prevention of
HIV Transmission
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

ART for HIV Prevention: The Hypothesis

 Initiation...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Observational Studies: ART Decreases
Risk of Transmi...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

HPTN 052: Immediate vs Delayed ART for
HIV Preventio...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

HPTN 052: HIV Transmission Reduced by
96% in Serodis...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

HPTN 052: HIV Transmission Reduced by
96% in Serodis...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Adherence and ART for HIV Prevention
 In HPTN 052, ...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

CDC: Breaks in the Continuum of Care in
HIV-Infected...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

2006 Recommendations From CDC:
Routine Opt-Out Testi...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

DHHS Guidelines 2013: When to Start
 ART recommende...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Limitations of Current Data on ART for HIV
Preventio...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Summary: ART as Prevention
 Initiation of effective...
Pre-Exposure Prophylaxis (PrEP)
for HIV-Uninfected Persons to
Reduce Risk of HIV Acquisition
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

What Is PrEP?
 For PrEP, an HIV-uninfected individu...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Pre- vs Postexposure Prophylaxis
After exposure to
H...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Pre- vs Postexposure Prophylaxis
Postexposure
prophy...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Pre- vs Postexposure Prophylaxis
Pre-exposure
prophy...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Pre- vs Postexposure Prophylaxis
HIV

HIV

HIV

For ...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Pre- vs Postexposure Prophylaxis
HIV

Pre-exposure p...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP Clinical Trials
 Phase III clinical trials of ...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP Trials Have Shown Efficacy in MSM,
Heterosexual...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Adherence Is a Key Determinant of PrEP
Trial Outcome...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Adherence Is a Key Determinant of PrEP
Trial Outcome...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Adherence Is a Key Determinant of PrEP
Trial Outcome...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP (Like ART) Works When Taken
Study

Blood Sample...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Partners PrEP: Comparable Efficacy in
Heterosexual M...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP Safety
 Rates of death, serious adverse events...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP Trials Found Decreasing Risk
Behavior Over Time...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP and HIV Drug Resistance
 Resistance rare (cons...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

FDA Approval of TDF/FTC Fixed-Dose
Combination for P...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Prescribing PrEP: CDC Interim Guidance
for MSM, Hete...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Limitations of Current Data
 Long-term adherence to...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Summary: PrEP
 TDF/FTC is approved as PrEP in combi...
Additional Issues
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Talking About Treatment and PrEP
 A common belief i...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Key Questions for ART as Prevention and
PrEP
 Cost
...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

PrEP Works Together With Other HIV
Prevention Strate...
Strengthening HIV Prevention in Primary Care
clinicaloptions.com/hiv

Putting This Together
HIV Prevention Effect With Hig...
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  • This slide lists the disclosure information of the faculty and staff involved in the development of these slides.
  • IDU, injection drug user.
  • ART, antiretroviral therapy.
  • ART, antiretroviral therapy.
  • ART, antiretroviral therapy; TB, tuberculosis; WHO, World Health Organization.
  • ART, antiretroviral therapy.
  • ART, antiretroviral therapy.
  • ART, antiretroviral therapy; CDC, Centers for Disease Control and Prevention.
  • CDC, Centers for Disease Control and Prevention.
  • ART, antiretroviral therapy; DHHS, US Department of Health and Human Services; HBV, hepatitis B virus; HCV, hepatitis C virus.
  • ART, antiretroviral therapy.
  • ART, antiretroviral therapy.
  • PrEP, pre-exposure prophylaxis.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir
  • FTC, emtricitabine; IDU, injection drug user; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • FTC, emtricitabine; IDU, injection drug user; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • FTC, emtricitabine; IDU, injection drug user; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • FTC, emtricitabine; IDU, injection drug user; PrEP, pre-exposure prophylaxis; TDF, tenofovir disoproxyl fumarate (prodrug); TFV tenofovir.
  • ART, antiretroviral therapy; IDU, injection drug user; PrEP, pre-exposure prophylaxis, TFV, tenofovir.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • GI, gastrointestinal; PrEP, pre-exposure prophylaxis.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • FDA, US Food and Drug Administration; FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • CDC, Centers for Disease Control and Prevention; FDC, fixed-dose combination; IDU, injection drug user; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • PrEP, pre-exposure prophylaxis.
  • ART, antiretroviral therapy; PrEP, pre-exposure prophylaxis.
  • ART, antiretroviral therapy; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection; TDF, tenofovir.
  • TFV, tenofovir.
  • A new options for hiv prevention slides.2013

    1. 1. New Options for HIV Prevention: The Role of Antiretrovirals This program is supported by an educational grant from
    2. 2. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
    3. 3. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Program Director and Core Faculty Jeanne Marrazzo, MD, MPH Professor of Medicine Division of Infectious Diseases University of Washington Medical Director Seattle STD/HIV Prevention Training Center Seattle, Washington Jared M. Baeten, MD, PhD Associate Professor, Departments of Global Health and Medicine University of Washington Seattle, Washington Kenneth Mayer, MD Infectious Disease Attending and Director of HIV Prevention Research Beth Israel Deaconess Medical Center Visiting Professor of Medicine Harvard Medical School Medical Research Director Fenway Community Health Boston, Massachusetts
    4. 4. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Other Faculty Who Contributed to This Program Laura H. Bachmann, MD, MPH Associate Professor Division of Infectious Diseases Department of Medicine Wake Forest University Health Sciences Winston-Salem, North Carolina Susan Buchbinder, MD Associate Clinical Professor Departments of Medicine, Epidemiology and Biostatistics Director, HIV Research Section San Francisco Department of Public Health San Francisco, California Connie Celum, MD, MPH Professor, Department of Global Health and Medicine University of Washington Seattle, Washington Khalil Ghanem, MD, PhD Associate Professor of Medicine Division of Infectious Diseases Johns Hopkins University School of Medicine Baltimore, Maryland
    5. 5. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Other Faculty Who Contributed to This Program Katherine Hsu, MD, MPH Associate Professor Department of Pediatrics Boston University School of Medicine Medical Director Division of STD Prevention and HIV Surveillance Massachusetts Department of Public Health Boston, Massachusetts Raphael J. Landovitz, MD, MSc Associate Professor of Medicine University of California, Los Angeles Los Angeles, California Albert Liu, MD, MPH Assistant Clinical Professor Department of Medicine University of California, San Francisco Director, HIV Prevention Intervention Studies HIV Research Section San Francisco Department of Public Health San Francisco, California
    6. 6. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Other Faculty Who Contributed to This Program Anne Rompalo, MD, ScM Professor of Medicine Division of Infectious Diseases Department of Medicine Johns Hopkins School of Medicine Baltimore, Maryland Mark Thrun, MD Associate Professor Division of Infectious Diseases Department of Medicine University of Colorado Director, HIV/STD Prevention and Control Denver Public Health Denver, Colorado
    7. 7. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Faculty Disclosures Jared M. Baeten, MD, PhD; Susan Buchbinder, MD; Connie Celum, MD, MPH; Khalil Ghanem, MD, PhD; Katherine Hsu, MD, MPH; Albert Liu, MD, MPH; Jeanne Marrazzo, MD, MPH; Anne Rompalo, MD, ScM; and Mark Thrun, MD, have no significant financial relationships to disclose. Laura H. Bachmann, MD, MPH, has disclosed that she has received funds for research support from Cepheid Raphael J. Landovitz, MD, MSc, has disclosed that he has received funds for research support from Gilead Sciences, GlaxoSmithKline, and ViiV. Kenneth Mayer, MD, has disclosed that he has received funds for research support from Bristol-Myers Squibb, Gilead Sciences, and Merck.
    8. 8. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv The Need for HIV Prevention: Continued HIV Risk in the US  Estimated new HIV infections in the United States for the most affected subpopulations, 2008-201 70 Diagnoses (%) 60 Male-to-male sexual contact Heterosexual contact IDU Male-to-male sexual contact and IDU Other 50 40 30 20 10 0 2008 2009 2010 Yr CDC. HIV in the United States: 2013. 2011
    9. 9. Treatment of HIV-Infected Persons for Prevention of HIV Transmission
    10. 10. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv ART for HIV Prevention: The Hypothesis  Initiation of ART results in early and sustained reductions in plasma and genital HIV levels  Led to the hypothesis that ART use would result in decreased infectiousness 35 Transmission Rate per 100 Person-Yrs  The quantity of HIV in plasma (and genital secretions) is the prime determinant of whether someone with HIV will transmit the virus to a sexual partner[1] 30 25 20 15 10 5 0 < 1. Quinn TC, et al. N Engl J Med. 2000;342:921-929. 0 40 9 00 99 00 49 ,0 ,0 99 -3 49 50 00 00 0≥ 4 35 00 0, 1 HIV-1 RNA (copies/mL)
    11. 11. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Observational Studies: ART Decreases Risk of Transmitting HIV Anglemyer A, et al. Cochrane Database Syst Rev. 2013;4:CD009153.
    12. 12. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv HPTN 052: Immediate vs Delayed ART for HIV Prevention in Serodiscordant Couples HIV-infected, sexually active serodiscordant couples; CD4+ cell count of the infected partner: 350-550 cells/mm3 (N = 1763 couples) Immediate ART Initiate ART at CD4+ cell count 350-550 cells/mm 3 (n = 886 couples) Delayed ART Initiate ART at CD4+ cell count ≤ 250 cells/mm3* (n = 877 couples) *Based on 2 consecutive values ≤ 250 cells/mm 3.  Primary efficacy endpoint: virologically linked HIV transmission  Primary clinical endpoints: WHO stage IV events, pulmonary TB, severe bacterial infection and/or death  Couples received intensive counseling on risk reduction and use of condoms Cohen MS, et al. N Engl J Med. 2011;365:493-505.
    13. 13. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv HPTN 052: HIV Transmission Reduced by 96% in Serodiscordant Couples Total HIV-1 Transmission Events: 39 (4 in immediate arm and 35 in delayed arm; P < .0001) Linked Transmissions: 28 Delayed Arm: 27 Immediate Arm: 1 P < .001 Cohen MS, et al. N Engl J Med. 2011;365:493-505. Unlinked or TBD Transmissions: 11 96% reduction in risk of HIV transmission within the partnership (95% CI: 73% to 99%)
    14. 14. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv HPTN 052: HIV Transmission Reduced by 96% in Serodiscordant Couples Total HIV-1 Transmission Events: 39 (4 in immediate arm and 35 in delayed arm; P < .0001) Linked Transmissions: 28 Delayed Arm: 27 Immediate Arm: 1 P < .001 Cohen MS, et al. N Engl J Med. 2011;365:493-505. Unlinked or TBD Transmissions: 11 Single transmission in patient in immediate ART arm believed to have occurred close to time therapy began and prior to suppression of genital tract HIV
    15. 15. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Adherence and ART for HIV Prevention  In HPTN 052, viral suppression was nearly universal in those receiving ART, reflecting intensive strategies to achieve nearly perfect adherence – Adherence counselors with detailed checklists; patients received extensive education about ART[1] – Adherence assessed at Wk 2, monthly x 3, and then quarterly  Real-world adherence to ART is not as high as achieved in HPTN 052 1. Cohen MS, et al. N Engl J Med. 2011;365:493-505. Supplementary appendix.
    16. 16. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv CDC: Breaks in the Continuum of Care in HIV-Infected Patients in the US  CDC study shows that only ~ 25% of US patients with HIV have suppressed HIV-1 RNA 100 82 Patients (%) 80 66 60 37 40 33 25 20 0 Diagnosed Linked to Care Hall HI, et al. JAMA Intern Med. 2013;17:1-7. Retained Prescribed Viral in Care ART Suppression
    17. 17. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv 2006 Recommendations From CDC: Routine Opt-Out Testing for HIV  Routine voluntary testing for patients aged 13-64 yrs in healthcare settings—not based on patient risk  Opt-out testing  No separate consent for HIV  Pretest counseling not required  Repeat HIV testing at least annually for persons at high risk Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.
    18. 18. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv DHHS Guidelines 2013: When to Start  ART recommended for all HIV-infected patients in US  Strength of recommendation varies depending on CD4+ count – CD4+ < 350 (AI); CD4+ 350-500 (AII); CD4+ > 500 (BIII)  Certain groups highlighted as priorities for therapy – History of AIDS-defining illness – Pregnancy – HIV-associated nephropathy – HBV coinfection (AII); HCV coinfection – At risk of transmitting HIV to sexual partners – Acute HIV infection DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. February 2013. ?
    19. 19. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Limitations of Current Data on ART for HIV Prevention  ART may mediate different degree of risk reduction when other modes of transmission (eg, needles, anal intercourse) taken into account  Adherence to lifelong ART may be difficult when initiated in asymptomatic individuals  Observational studies of the effect of ART on transmission among HIV serodiscordant couples have shown lower HIV risk reduction, likely as a result of lower adherence to ART[1]  28% of infections in HPTN 052 occurred from outside of study partnerships, for which ART use by the HIV-infected partner offered no protection[2] 1. Anglemyer A, et al. Cochrane Database Syst Rev. 2013;4:CD009153. 2. Cohen MS, et al. N Engl J Med. 2011;365:493-505.
    20. 20. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Summary: ART as Prevention  Initiation of effective ART results in a substantial decrease in HIV infectiousness and transmission risk  Adherence (with viral suppression) is key to preventive effects of ART  Prescribing guidelines now include risk of transmission as an indication to initiate ART – However, no formal indication for prevention of transmission exists for any antiretroviral  Providers should talk about prevention as part of ART’s benefits
    21. 21. Pre-Exposure Prophylaxis (PrEP) for HIV-Uninfected Persons to Reduce Risk of HIV Acquisition
    22. 22. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv What Is PrEP?  For PrEP, an HIV-uninfected individual takes antiretroviral medication(s) before potential HIV exposure  The idea of providing a medication as prophylaxis against an infectious disease is well established – For example, taking medications for diseases such as malaria before traveling to high-risk areas reduces risk of infection establishing itself if exposure occurs
    23. 23. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Pre- vs Postexposure Prophylaxis After exposure to HIV, infection may become established HIV 0 hr HIV infection 36 hrs 72 hrs 1 mos 3 mos 5 mos
    24. 24. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Pre- vs Postexposure Prophylaxis Postexposure prophylaxis— initiated soon after an exposure—reduces the chance of infection HIV HIV infection Postexposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos
    25. 25. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Pre- vs Postexposure Prophylaxis Pre-exposure prophylaxis begins treatment earlier— before exposure— which might increase the prophylactic effect HIV HIV infection Pre-exposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos
    26. 26. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Pre- vs Postexposure Prophylaxis HIV HIV HIV For persons with ongoing/ repeated HIV exposure, intermittent postexposure prophylaxis may not be sufficient 0 hr Postexposure prophylaxis 36 hrs 72 hrs 1 mos 3 mos 5 mos
    27. 27. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Pre- vs Postexposure Prophylaxis HIV Pre-exposure prophylaxis might protect against a period of ongoing risk by having a continuing level of medication available HIV HIV Pre-exposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos
    28. 28. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP Clinical Trials  Phase III clinical trials of PrEP tested daily oral TDF-based tablets (alone or in combination with FTC)  Factors that supported testing of TDF-based PrEP in clinical trials – Potency: rapid antiretroviral activity – Safety: high tolerability, substantial treatment safety experience – Ease: once-daily dosing, few drug–drug interactions – Preclinical/early clinical evidence: animal model data found high efficacy of PrEP for HIV protection[1] 1. Garcia-Lerma JG, et al. Current Opin HIV AIDS. 2012;7:505-513.
    29. 29. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP Trials Have Shown Efficacy in MSM, Heterosexual Men and Women, and IDUs Trial Population/Setting Intervention HIV Infections, n PrEP Placebo 64 Reduction in HIV Infection Rate, % (95% CI) iPrEX[1] (N = 2499) MSM, transgender women, 11 sites in US, South America, Africa, Thailand TDF/FTC 36 44 (15-63) Partners PrEP[2] (N = 4747) Serodiscordant couples in Africa TDF 17 TDF/FTC 13 52 75 (55-87) TDF2[3] (N = 1219) Heterosexual males and females in Botswana TDF/FTC 9 24 62 (21-83) Thai IDU[4] (N = 2413) Volunteers from 17 drug treatment centers in Thailand TDF 17 33 49 (10-72) 67 (44-81) 1. Grant RM, et al. N Engl J Med. 2010;363: 2587-2599. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 3. Thigpen MC, et al. N Engl J Med. 2012;367:423-434. 4. Choopanya K, et al. Lancet. 2013;381:2083-2090.
    30. 30. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Adherence Is a Key Determinant of PrEP Trial Outcomes Study Detection of TFV in Plasma, % HIV Seroconverters HIV Uninfected iPrEx[1] 51 Partners PrEP[2] (TDF/FTC arm) 81 Thai IDU[3] 67 In the large iPrEx, Partners PrEP, and Thai IDU studies, TFV was detected in blood samples of the majority of subjects who remained HIV uninfected during the study 1. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 3. Choopanya K, et al. Lancet. 2013;381:2083-2090.
    31. 31. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Adherence Is a Key Determinant of PrEP Trial Outcomes Study Detection of TFV in Plasma, % HIV Seroconverters HIV Uninfected iPrEx[1] 9 51 Partners PrEP[2] (TDF/FTC arm) 25 81 Thai IDU[3] 39 67 By contrast, TFV was detected in only a minority of subjects who acquired HIV, arguing that adherence to taking the study medication was related to remaining HIV uninfected 1. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 3. Choopanya K, et al. Lancet. 2013;381:2083-2090.
    32. 32. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Adherence Is a Key Determinant of PrEP Trial Outcomes Study Detection of TFV in Plasma, % HIV Seroconverters HIV Uninfected iPrEx[1] 9 51 Partners PrEP[2] (TDF/FTC arm) 25 81 Thai IDU[3] 39 67 This difference in TFV detection translated into a relative risk reduction of acquiring HIV: iPrEx: 92% (95% CI: 40% to 99%; P < .001) Partners PrEP TDF/FTC: 90% (95% CI: 56% to 98%; P = .002) Thai IDU: 70% (95% CI: 2% to 91%; P = .04) 1. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 3. Choopanya K, et al. Lancet. 2013;381:2083-2090.
    33. 33. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP (Like ART) Works When Taken Study Blood Samples With TFV Detected, % HIV Protection Efficacy in Randomized Comparison,% Partners PrEP[1] 81 75 TDF2[2] 80 62 iPrEx[3] 51 44 Thai IDU[4] 67 49 < 30 No HIV protection FEM-PrEP[5] and VOICE[6] 2 additional trials of PrEP (FEM-PrEP and VOICE), both conducted among high-risk African women, did not demonstrate protection against HIV; in both trials, PrEP adherence was very low (< 30%) 1. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 2. Thigpen MC, et al. N Engl J Med. 2012;367:423-434. 3. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. 4. Choopanya K, et al. Lancet. 2013;381: 2083-2090. 5. Van Damme L, et al. N Engl J Med. 2012;367:411-422. 6. Marrazzo J, et al. CROI 2013. Abstract 26LB.
    34. 34. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Partners PrEP: Comparable Efficacy in Heterosexual Men and Women Arm Groups Efficacy, % (95% CI) TDF Women (n = 595) Men (n = 984) 71 (37-87) 63 (20-83) Women (n = 566) Men (n = 1010) 66 (28-84) 84 (54-94) TDF/FTC Baeten JM, et al. N Engl J Med. 2012;367:399-410. P Value vs Placebo .002 .01 .005 < .001
    35. 35. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP Safety  Rates of death, serious adverse events, and laboratory abnormalities (including renal dysfunction) low and not significantly different between those receiving PrEP and those receiving placebo  PrEP was well tolerated – Adverse events occurred in minority of subjects – GI adverse events (eg, nausea) more common in those receiving PrEP than placebo – Occurred in < 10% and primarily during the first month only (PrEP “start up” symptoms)  PrEP associated with a small change (~ 1%) in bone mineral density but without increased risk of fracture
    36. 36. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP Trials Found Decreasing Risk Behavior Over Time iPrEx[1] Placebo FTC/TDF 80 60 40 20 Placebo FTC/TDF TDF 50 Subjects Reporting Unprotected Sex (%) Subjects Reporting Unprotected Receptive Anal Sex (%) 100 Partners PrEP[2] 0 40 30 20 10 0 0 24 48 72 96 120 144 Wks Since Randomization 1. Grant RM, et al. N Engl J Med. 2010;363: 2587-2599. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 0 3 6 9 12 15 18 21 24 27 30 33 Follow-up Time (Mos)
    37. 37. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP and HIV Drug Resistance  Resistance rare (consistent with subjects who acquired HIV not taking PrEP) – Exception: those with undiagnosed (seronegative) acute HIV infection at time PrEP was initiated  Resistance mutations seen: K65R (TDF) or M184V/I (FTC) Liegler T, et al. CROI 2011. Abstract 97LB. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Baeten JM, et al. N Engl J Med. 2012;367:399-410 (supplementary appendix). Thigpen MC, et al. N Engl J Med. 2012;367:423-434 (supplementary appendix). Choopanya K, et al. Lancet. 2013;381:2083-2090.
    38. 38. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv FDA Approval of TDF/FTC Fixed-Dose Combination for PrEP  In July 2012, the FDA approved the fixed-dose combination TDF/FTC as PrEP in combination with safer sex practices to reduce the risk of sexually acquired HIV infection in adults at high risk  Must be used only by individuals who are confirmed to be HIV negative – Prior to prescribing the drug and at least every 3 mos during use  Once-daily dosing (no evidence for any other prescribing frequency)  Manufacturer required to have training and education program to assist prescribers in counseling individuals who are receiving or considering TDF/FTC for PrEP – Patient assistance available: 855.330.5479
    39. 39. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Prescribing PrEP: CDC Interim Guidance for MSM, Heterosexual Couples, IDUs Component Recommendation Risk assessment  PrEP indicated for those at high HIV risk Eligibility  HIV negative, adequate renal function Dosing  1 FDC tablet, once daily Follow-up  Testing for HIV every 3 mos  Counseling on risk reduction and testing creatinine at 3 mos and then annually  Testing for STIs every 6 mos, even if asymptomatic Discontinuation  PrEP not meant for lifelong administration but rather for periods of highest risk CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68. CDC. MMWR Morb Mortal Wkly Rep. 2012;61:586589. CDC. MMWR Morb Mortal Wkly Rep. 2013;62;463-465.
    40. 40. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Limitations of Current Data  Long-term adherence to PrEP and long-term health effects of TDF/FTC in HIV-negative persons and HIV seroconverters not known  Adherence, risk behavior, and PrEP interest likely to be different now that PrEP HIV protection benefits known CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68. Grant RM, et al. N Engl J Med. 2010;363:25872599.
    41. 41. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Summary: PrEP  TDF/FTC is approved as PrEP in combination with safer sex practices to reduce the risk of sexually acquired HIV infection in adults at high risk (July 2012)  Adherence appears to be key to PrEP efficacy  Providers should be prepared to do risk assessment, counseling, and prescribe PrEP for high-risk individuals
    42. 42. Additional Issues
    43. 43. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Talking About Treatment and PrEP  A common belief is that antiretroviral medications are awful; this delays treatment and is a prominent patient concern for PrEP  New messages from providers are needed
    44. 44. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Key Questions for ART as Prevention and PrEP  Cost  Uptake  Adherence  Sexual behavior  Impact  Resistance
    45. 45. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv PrEP Works Together With Other HIV Prevention Strategies  Example from Partners PrEP Study: package of HIV prevention services, including ongoing risk-reduction counseling, HIV testing, ART, treatment of STIs, and other strategies plus PrEP synergize to maximally reduce HIV risk HIV Incidence 10% to 15%/yr 2%/yr 0.5%/yr Serodiscordant Couples Outside of Clinical Trials[1] Partners PrEP Placebo Arm[2] Partners PrEP TDF/FTC Arm[2] 1. Quinn TC, et al. N Engl J Med. 2000;342:921-929. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410.
    46. 46. Strengthening HIV Prevention in Primary Care clinicaloptions.com/hiv Putting This Together HIV Prevention Effect With High Adherence Antiretroviral treatment for HIV prevention PrEP for HIV prevention 96% (With high adherence as measured by TFV levels in iPrEx and Partners PrEP) (HPTN 052, near-perfect adherence) 90% to 92% 2 incredibly powerful prevention strategies

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