Attendees will be able to:

Transcription

1 A. Kay Kalousek, DO, MS, FACOFP April 21, 2017 Attendees will be able to: List strategies for prevention of HIV infection Explain the pharmacology of TDF/FTC related to PrEP Assess an individual patient s risk for HIV infection Evaluate patients at risk for adverse events or outcomes related to PrEP Renal function Chronic Hepatitis B Disorders of bone Pregnancy 1

2 Attendees will be able to: Order appropriate laboratory testing prior to starting PrEP and manage as needed Provide patient education for patients who are candidates for PrEP Symptoms of acute HIV Importance of adherence Additional strategies for HIV & STI risk reduction Potential side effects/adverse reactions Monitor PrEP and evaluate patient s continued risk for HIV and need for PrEP Behavioral Sexual abstinence Sexual partner reduction/monogamy Consistent use of condoms Decreased substance use Harm reduction strategies for drug users 2

3 Lifetime Risk of HIV Diagnosis Varies by Region of the U.S. 384 West Midwest Northeast 527 (VT) (NJ) 96 (DE) 13 (DC) 49 (MD) 411 (NH) 121 (MA) 143 (RI) 139(CT) South High HIV Risk Moderately High HIV Risk Moderately Low HIV Risk Low HIV Risk People living in the South are more likely to be diagnosed with HIV over the course of their lifetime than other Americans, with the highest risk in Washington, DC (1 in 13) and the lowest risk in North Dakota (1 in 670) U.S. Centers for Disease Control and Prevention. Feb, 23, Available at: 5 Estimated New HIV Infections in the US, by Age, % 7,084 7,510 Estimated New HIV infections, n ,698 5,437 4,194 3,418 3,302 3,010 1,860 17% < >65 Persons <25 and >50 years old make up nearly 40% of new HIV infections U.S. Centers for Disease Control and Prevention. HIV Surveillance Report, Available at: Accessed November 29,

4 Percentage of People with HIV and Percentage of HIV Transmissions at Each Stage of the Care Continuum, U.S. and Puerto Rico, % 90% 80% Percentage 70% 60% 50% 40% 30% 20% People with viral suppression People prescribed ART without viral suppression People receiving care but not prescribed ART People with diagnosis and not receiving care People with undiagnosed HIV infection 10% 0% 13 People living with HIV Infection 23 Transmissions 92% of new HIV infections are transmitted from HIV-positive persons who are undiagnosed or diagnosed but not in care Frieden T, et al. N Engl J Med 2015;373: Biologic Vaccine: No effective preventative vaccine currently available Pharmacologic: Use of TDF FTC for Pre Exposure Prophylaxis (PrEP) 4

5 High-Impact HIV Prevention Incorporates Multiple Interventions Biomedical Interventions Circumcision Behavioral Interventions Patient and Partner Education Testing and Treatment of STIs Sex Partners Sharing Needles Post-Exposure Prophylaxis (PEP) TRUVADA for PrEP HIV Prevention Strategies Having Only One Sexual Partner Correct and Consistent Condom Use TasP Older Age at Initiation of Sexual Activity Prevention of Motherto-Child Transmission Abstaining From Sexual Intercourse Cohen M, et al. J Int AIDS Soc. 2008;11:4. Cohen M, et al. Sexual HIV Transmission and Its Transmission. Accessed March 10, PARTNER Study: Treatment as Prevention HIV Transmission Rates in HIV Serodiscordant Couples, with Suppressed HIV+ Partner and Condomless Sex Multicenter, European, observational study in serodiscordant couples [888 couples (548 heterosexual, 340 MSM)] Couples were assessed every 6 months to ensure: HIV-infected partner remained virally suppressed (HIV RNA <200 c/ml) HIV-uninfected partner was not using PrEP or PEP Couple was having condomless vaginal or anal sex HIV-Negative Members of Eligible Couples Reporting Specific Sex Act, % Couple-Years of Follow-up Upper 95% CI Heterosexual women Vaginal sex w/ ejaculation Vaginal sex w/o ejaculation Heterosexual men Vaginal sex MSM Insertive anal sex Receptive anal sex w/ ejaculation Receptive anal sex w/o ejaculation No documented HIV within-couple transmissions. Longer-term follow-up is necessary to provide more precise estimates of risk. Rodger A, et al. JAMA. 2016;316(2): Rate of Within-Couple Transmission, per Couple-Year of Follow-up 10 5

6 HIV Incidence in San Francisco, New HIV Diagnoses Annual HIV diagnoses, n San Francisco established: Year Treatment of all HIV-positive people regardless of CD4 Truvada for PrEP program with an estimated 6,000 people taking PrEP There has been a 44% drop in new HIV cases diagnosed from 2012 to 2015 San Francisco Department of Public Health, Population Health Division,. HIV Epidemiology Annual Report Fixed dose combination of two medications used to treat HIV Tenofovir disoproxil fumarate emtricitabine (TDF FTC; Truvada) Reduction in HIV transmission: >90% (up to 96%) in patients with high risk for infection through sexual contact >70% in patients using injection drugs Patient must be committed to daily medication adherence and regular medical follow up and monitoring. 6

7 Combination of a nucleoside reverse transcriptase inhibitor (emtricitabine) + a nucleotide RT inhibitor (tenofovir) Emtricitabine: cytosine analog Tenofovir: adenosine 5 monophosphate analog Both drugs interfere with viral RNA dependent DNA polymerase and this prevents viral RNA from becoming viral DNA. PrEP: Linkage to Care Identifying Potential PrEP Providers (or Providers who Might Refer for PrEP) Primary care providers who practice in communities at high risk for HIV HIV care providers Substance abuse or mental health providers Sexual health service providers STD clinics, family planning settings OB / GYN Student Health Providers 14 7

8 PrEP: Linkage to Care Information That Providers Need to Know PrEP science Who is at risk for HIV locally How to prescribe PrEP Resources and education available ICD -10 Payment options Sexual history taking 15 Detailed sexual and drug use history: Is patient at high risk for HIV infection? Sex with men, women, or both Sexual activities How many partners during the past 3 months Percentage of condom use during this time Serodiscordant partner(s) or HIV status unknown Sex under the influence: drugs and/or alcohol. 8

9 Sex with an IV drug user Sex with transgender woman Transactional sex STIs during the preceding 6 months Gonorrhea Chlamydia Syphilis Hepatitis B Hepatitis C Herpes HPV Alcohol abuse Eating disorder Endocrine disorder (diabetes, thyroid, etc.) Renal problems Osteopenia/osteoporosis Family history of bone disorders Chronic NSAID use Hepatitis B 9

10 General physical examination with attention to any positive findings including: Elevated blood pressure Swelling of extremities Liver enlargement Injection scars (tracks) HIV rapid antibody testing HIV 1/2 Fourth Generation Ab/Ag testing HIV viral RNA Comprehensive metabolic profile (CMP) Glucose Renal function testing: creatinine/gfr Electrolytes Calcium Liver function testing 10

11 Complete blood count (CBC) Urinalysis Hepatitis A, B, C RPR with reflex testing if positive STI testing for gonorrhea and chlamydia Rectal swab, throat swab, urine Cervical swab (for females) Baseline dexa scan for patients with or at risk for osteopenia/osteoporosis Pregnancy testing Give a copy to patient at each PrEP encounter Sections should include: FAQ type information Length of time until PrEP is effective (7 21 days) Information regarding symptoms that may point to acute HIV infection PrEP medication (TDF FTC) potential SE and AR Emphasis on adherence (no refills without visit) and continued condom use while taking PrEP Document in chart that information sheet was given to patient and discussed during the visit 11

12 Patient should not receive PrEP medication until negative rapid HIV testing results are back TDF FTC is a significant component of HIV treatment, but HIV infected patients taking TDF FTC alone run the risk of HIV resistance Tenofovir: high genetic barrier to resistance (K65R mutation is uncommon) Emtricitabine: low genetic barrier to resistance (M184V mutation) If HIV negative, prescription for fixed dose TDF FTC 300 mg 200 mg (Truvada) can be given Patients can experience elevation of creatinine and decrease of glomerular filtration rate (GFR) Additive effect of medications such as acyclovir, NSAIDs, other antiviral medications If patient develops elevated creatine, proteinuria and/or glycosuria, consider Fanconi syndrome: impaired proximal tubular function Urinary wasting of phosphorous (osteomalacia) Glycosuria Renal tubular acidosis (bicarbonate loss) 12

13 Patients with chronic hepatitis B need to be informed that adherence to therapy is critical since tenofovir can be used as first line therapy for hepatitis B, but stopping therapy can lead to flare of hepatitis B Treatment for hepatitis B can be range from years to lifelong Patients who stop PrEP should be considered for transition of therapy for hepatitis B alone Baseline dexa scan for patients with history of or risk factors for osteopenia or osteoporosis If PrEP is started, consider repeat dexa scan at 6 months and 12 months after initiation of therapy Vitamin D testing and replacement as indicated Calcium intake Sun exposure 13

14 Women with potential for pregnancy should receive pregnancy testing at baseline and each follow up encounter. PrEP is considered to be safe for use in pregnancy (category B) but it is unclear if the tenofovir component can cause issues with fetal bone development Risk of HIV infection must be weighed with potential risk to the developing fetus. Typically if history, physical, and lab findings are normal first follow up is 4 to 6 weeks after starting and every 3 months thereafter Reassess patient s continued need for PrEP Assess if patient is having any signs of signs of acute HIV infection or SE or AR with PrEP Provide education regarding safer sexual practices Order laboratory testing: HIV rapid antibody testing, HIV 1/2 4 th generation Ab/Ag testing, HIV RNA quantitative, renal function, urinalysis, gonorrhea, chlamydia, syphilis, (+/ hepatitis C), pregnancy testing, etc 14

15 Treat STIs as needed Manage other findings as needed If hepatitis B positive, obtain hep B viral load. Stress importance of adherence to therapy and potential for flare of hep B is therapy stopped Manage hepatitis C if positive Watch for change in renal function and consider discontinuation of therapy if GFR <60 or decreases by more than 20% Vaccinations: Hep A & B, Meningitis, others as indicated Assess patient s risk for HIV infection Assess patient s understand of what PrEP does and does not prevent and provide education Assess patient s willingness and ability to be adherent to daily medication regimen Assess patient s ability for regular follow up Medical history and physical examination Baseline laboratory testing Monitor and re assess at least every 3 months 15

16 PrEP: Linkage to Care Potential PrEP Navigation Protocol IDENTIFICATION AND EDUCATION 1. Thoroughly discuss sexual history / HIV risk 2. Educate individual at risk for HIV on all prevention options, including PrEP ASSESSMENT 3. Assess PrEP treatment readiness 4. Assess mental health or substance abuse treatment needs 5. Assess insurance status of patient 6. Assist with any enrollment paperwork that might be necessary 7. Consider providing baseline HIV / STD screening labs REFERRAL AND FOLLOW-UP 8. Actively refer to a PrEP prescriber 9. Assess need for ongoing adherence support or case management 10. Follow-up to assess status of referral 31 PrEP Landscape in the U.S. PrEP is One Component of High-Impact HIV Prevention Patient and Education partner education Behavioral Interventions Aim: to lower the number of partners, alter risk-taking behavior Sexual Partners partners Sharing Needles needles Refraining from Sex sex Older Age age at Initiation initiation of Sexual sexual Activity activity Having only one sexual partner Male circumcision High-impact HIV Prevention Correct & Consistent consistent Condom condom use Use Treatment of STIs PEP PrEP HIV treatment as prevention Biomedical Interventions Aim: to reduce the efficiency of HIV transmission or to shorten the duration of infectiousness Prevention of of mother-to-child transmission Cohen M, et al. Sexual HIV Transmission and Its Transmission. Available at: Accessed December 8, 2011 Cohen M, et al. J Int AIDS Soc 2008;11:4 (Adapted) 32 16

17 Other classes or combinations of medications: Integrase inhibitors Entry inhibitors Protease inhibitors Long acting injectable medications Significantly decreases issues related to adherence Preferred by most patients in early trials Vaginal ring for women PrEP: Clinical Support PrEP Provider Resources U.S. PHS/CDC Clinical Practice Guidelines for PrEP HIV Prevention Capacity Building Assistance Providers HRSA-funded AIDS Education and Training Centers aidsetc.org UCSF Clinical Consultation Center NACCHO s PrEP for Local Health Departments Educational Series