BIOMEDICAL PREVENTION: NON-OCCUPATIONAL POST EXPOSURE PROPHYLAXIS (NPEP) GUIDELINES

Transcription

1 BIOMEDICAL PREVENTION: NON-OCCUPATIONAL POST EXPOSURE PROPHYLAXIS (NPEP) GUIDELINES ORLANDO O. HARRIS, PHD, RN, FNP, MPH POST-DOCTORAL FELLOW, CENTER FOR AIDS PREVENTION STUDIES, DEPARTMENT OF MEDICINE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO JUNE 22, 2017

2 CME Disclosures: Planning Committee And Speaker Speaker: The following speaker has nothing to disclose in relation to this activity: Orlando O. Harris, PHD., RN, FNP, MPH

3 Howard University CME Accreditation Sponsor Accreditation: Howard University College of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Credits for Physicians: Howard University College of Medicine, Office of Continuing Medical Education, designates this live activity for a maximum of 1.0 AMA PRA Category I Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Goulda A. Downer, PHD, RD, LN, CNS Principal Investigator/Project Director

4 CME Disclosures: Planning Committee And Speaker AETC-Capitol Region Telehealth Project Planning Committee: The following committee members have nothing to disclose in relation to this activity: Goulda A. Downer, PhD, RD, LN, CNS John I. McNeil, MD Jean Davis, PHD,DC, PA, MSCR Denise Bailey, MED Speaker: The following speaker has nothing to disclose in relation to this activity: Orlando O. Harris, PHD, FNP, MPH

5 Howard University CME Accreditation Requirements For Internet Viewers Intended Audience: Health service providers: Physicians, Physician Assistants, Nurse Practitioners, Pharmacists, Dentists, Nurses, Social Workers, Case Managers and other Clinical Personnel. Webinar Requirements: A computer, phone, etc., with internet accessibility and a telephone line. ØYour presence on the call must be acknowledged at the start of each session. Please log in for the session announce your name loud and clear at the beginning of the session. ØYou will not be able to receive CME credits if you leave the session early. ØAt the end of the Webinar our Training Coordinator will a CME Evaluation Survey. ØAll participants are required to complete and return the CME Evaluation Survey at the end of each session. It may be scanned and ed back to den_bailey@howard.edu, or faxed to: AETC-Capitol Region Telehealth Project (FAX#: ) ATTN: Project Coordinator. Please indicate in your or FAX if you would like to receive CMEs.

6 TEST YOUR KNOWLEDGE 6

7 Test Your Knowledge Question #1 A patient is started on npep and the baseline HIV test comes back showing the person is positive. The clinician should: A. Immediately stop the npep regimen B. Request a confirmatory HIV test C. Add an additional antiretroviral to the npep regimen D. Repeat the test using a rapid HIV test

8 Test Your Knowledge Question #2 Which of the following patient with HIV has the highest risk of infecting their partner? A. An elite controller B. A patient suppressed on a combination regimen C. A patient with acute HIV infection unaware of their status D. A patient who has been infected for about a year but is unaware of their status

9 Test Your Knowledge Question #3 Which regimen is preferred to npep? A. A triple nucleoside combination B. Dolutegravir, tenofovir, emtrictibine C. Atripla D. Kaletra/Combivir

10 TEST YOUR KNOWLEDGE QUESTION #4 A subject presents to the ER for testing suspecting they may have acute HIV infection. What single test would be most useful in determining this? A. A viral load (HIV RNA) B. A western blot C. A fourth-generation HIV test D. A home HIV test

11 BIOMEDICAL PREVENTION: NON-OCCUPATIONAL POST EXPOSURE PROPHYLAXIS (NPEP) GUIDELINES

12 LEARNING OBJECTIVES Upon completion of this webinar, participating providers will have the enhanced ability to: 1.Discuss CDC guidelines for non-occupational HIV post-exposure prophylaxis (npep) 2.Discuss timing of Post Exposure Prophylaxis treatment initiation 3.Describe post-exposure prophylaxis therapy and side effects 4.Explain transmission risks for various npep exposures. 5.Identify the dynamics of HIV transmission and early infections and select tests likely to be most accurate based on the patient's stage of infection 6.Assess the level of risk of transmission for a patient presenting for npep

13 TIME-COURSE OF HIV INFECTION SEROLOGY

14 ALGORITHM FOR HIV TESTING

15 Ø Viral load of the source RISK FOR TRANSMISSION Ø STI s in the source or subject Ø Type of sex Ø Type of bodily fluids

16 HIGH-RISK FLUIDS Exposure of mucous membranes in the vagina, urethra, rectum, mouth, eyes, non-intact skin to: Ø Blood Ø Semen Ø Vaginal Fluids

17 LOW-RISK FLUIDS Ø Urine Ø Saliva Ø Sweat Ø Nasal secretions Ø Tears

18 RISK OF HIV TRANSMISSION BY TYPE OF SEX Sexual Type of Exposure Risk per 10,000 Exposures Receptive anal intercourse 50 Receptive penile-vaginal intercourse 10 Insertive anal intercourse 6.5 Insertive penile-vaginal intercourse 5 Receptive oral intercourse Insertive oral intercourse Low a Low a

19 INDICATIONS FOR NPEP Ø Receptive or insertive vaginal or anal sex Ø Sharing needles for drug-use Ø Injuries with exposure to blood or other high-risk fluids from a person known to be HIV+ or of unknown status Ø npep is NOT indicated for low-risk exposures!

20 FACTORS TO CONSIDER IN NPEP REGIMEN ØEfficacy ØCost ØTolerability/Toxicity ØAdherence

21 EVIDENCE FOR NPEP GUIDELINES Ø There are very limited data of any value suggesting any potentially suppressive regimen is better than another Ø There are no clinical studies that conclusively validate the use of nonoccupational PEP; there are a plethora of variables and any type of controlled study would constitute grave ethical concerns Ø Over the years, the preferred regimens for initiating ART are also recommended for non-occupational PEP

22 PREFERRED REGIMENS Ø Tenofovir/Emtricitibine Plus Ø Raltegravir or Dolutegravir Ø Boosted protease inhibitor Ø Atazanavir (300/100) or Darunavir (800/100) Ø Treatment should be initiated ideally with 36 hours of exposure, certainly with 72 hours, and continued for 28 days

23 PREFERRED REGIMENS- SUMMARY

24 HIV SCREENING AFTER INITIATING NPEP Ø Perform baseline testing Ø Perform testing of the source (if possible) Ø Test patient at baseline, week four post-exposure and week 12

25 OTHER TESTS WHILE ON NPEP ØClinical chemistries for monitoring patients on npep at baseline, week 2 and 4 post-exposure -liver enzymes, BUN, creatinine, CBC ØTest for other STI s at baseline - gonorrhea/chlamydia NAAT - syphilis RPR ØHCV/HBV ØPregnancy test

26 CASE STUDY DISCUSSION

27 CASE STUDY Ø Patient reports to an emergency room and states that he had just had receptive anal intercourse within 70 hours with his newly-seropositive partner and had engaged in numerous encounters with his partner over the last two months Ø Patient tested negative by rapid test in the ER Ø He request to start npep immediately. Case submitted by Demetre C Daskalakis MD, MPH to IAS-USA

28 WHAT WOULD YOU DO?

29 CONSIDER. Ø Sensitivity and specificity of rapid HIV tests Ø Proper use and interpretation of results Ø Detection of acute HIV infection by rapid tests Ø Is the subject a candidate for npep?

30 CASE STUDY (CON T) ØPatient started on npep ØRegimen initiated was Dolutegravir, tenofovir and emtricitibine Baseline Lab test Rapid HIV test AST ALT creatinine BUN CBC Result/Value negative 98 IU/L (10-35 IU/L) 101 IU/L (9-60 IU/L) normal normal normal

31 CASE STUDY (CON T) ØER clinician concerned that npep was started based on patient s prior history and concerned that partner may have acute HIV infection ØTransaminases are elevated ØID consults advise to do a viral load (HIV RNA) on the patient and screen for acute HCV/HBV infection

32 WHAT WOULD YOU DO?

33 CASE: SCREENING FOR STI S Patient s Laboratory Values at Follow-Up Visit Laboratory Measure or Test Oropharyngeal gonorrhea Rectal gonorrhea Rectal chlamydia Urine gonorrhea Urine chlamydia Syphilis immunoglobulin Hepatitis B virus (HBV) surface antibody HBV surface antigen Hepatitis C virus (HCV) serology Plasma HCV RNA Plasma HIV RNA Result Negative Positive Negative Negative Negative Nonreactive Positive Negative Negative Below limit of detection 900 copies/ml

34 CASE STUDY (CON T) Ø What do the previous series of labs indicate about the HIV status of this patient? Ø What other issues need to be managed?

35 CASE STUDY: CONCLUSION Ø What were the risk factors for transmission in this case? Ø The gonorrhea was treated with ceftriaxone 250 mg IM, and azithromycin 1g orally Ø The npep regimen was changed to raltegravir, tenofovir, emtricitibine Ø Does the very early initiation of a potent, suppressive regimen in the patient influence the natural history of the infection in this patient?

36 FACTORS TO CONSIDER IN NPEP REGIMEN- SUMMARY

37 OTHER FACTORS TO CONSIDER

38 MALE CIRCUMCISION AS A STRATEGY FOR REDUCING HIV TRANSMISSION RISK

39 RATIONALE Ø The foreskin contains a mucosal surface on the penis Ø This mucosal surface can be a gateway for pathogens, particularly sexually-transmitted ones, into the body Ø Dendritic cells and other APC s maintain surveillance for pathogens that breach the foreskin mucosal surface Ø Dendritic cells that encounter HIV can carry the virus almost in a Trojan Horse style to infect T lymphocytes in lymphoid tissues Ø Three RCT demonstrate efficacy of male circumcision in reducing risk of HIV transmission by 50-60%

40 SCALE-UP OF MALE CIRCUMCISION IN AFRICAN COUNTRIES TABLE 1. Voluntary medical male circumcisions (VMMCs) performed by CDC-supported programs, by country and fiscal year, Country No. of VMMCs Total Botswana 8,590 8,590 Kenya* 104, , , ,752 Malawi 778 7,420 8,198 Mozambique 4,009 18,472 68,924 91,405 Namibia 1,197 5,292 5,965 12,454 South Africa 3,820 15,574 80, ,095 Tanzania 1,519 50,325 49, ,600 Uganda 9,052 57, , ,812 Zambia 13,368 33,841 58, ,518 Total 137, , ,604 1,020,424 * Kenya's data for 2010 and 2011 are reported from January December, but data from 2012 are from October September. Malawi's data are from APR results and CDC Malawi's partner reports for South Africa's data are reported from January December for Tanzania's data for are from APR reports and Tanzania's national database. Source: President's Emergency Plan for AIDS Relief (PEPFAR) annual progress report (APR) submissions for CDC-supported partners, for fiscal years October 1 September 30, except where noted.

41 SEXUALLY-TRANSMITTED INFECTIONS AND HIV TRANSMISSION ØSTI s result in inflammation and migration of immune cells into the genital tract. Inflammatory cytokines increase HIV replication and make immune cells more susceptible to HIV infection ØGenital Ulcer Disease (GUD) caused by STI s (HSV-1,2, syphilis) compromise the integrity of the mucosal barrier and facilitate HIV transmission

42 SEXUALLY-TRANSMITTED INFECTIONS AND HIV TRANSMISSION ØSTI s (e.g. gonorrhea) can increase the amount of HIV in semen and vaginal fluids up to 10x increasing exposure to the partner ØReproductive Tract Infections (RTI; bacterial vaginosis, Trichomonas) increase HIV in vaginal fluids and risk of transmission ØSTI s and RTI s increase the risk of HIV transmission from seropositive individuals and also HIV acquisition by a seronegative individual

43 URETHRITIS Ø HIV-1-seropositive men with urethritis had HIV-1 RNA concentrations in seminal plasma eight times higher than those in seropositive men without urethritis (12.4 vs 1.51 x 10 4 copies/ml, p = 0.035). CD4 counts and concentrations of blood plasma viral RNA were similar Ø Gonorrhoea was associated with the greatest concentration of HIV-1 in semen Ø Treatment of STI decreased the concentration of HIV-1 RNA in semen significantly (from 12.4 x 10 4 copies/ml to 8.91 x 10 4 copies/ml at 1 week [p = 0.03] and 4.12 x 10 4 copies/ml at 2 weeks [p = ]) Cohen et al., Lancet,2007,349(9069):

44 HSV-2 AND HIV CO-INFECTION ØA causative agent of genital ulcer disease ØHSV-2 is suspected to be a major driver of the HIV epidemic in Africa

45 BACTERIAL VAGINOSIS AND HIV Ø Lactobacillus sp. predominate in the vaginal normal flora Ø Bacterial vaginosis is characterized by alterations in the vaginal microbiome and colonization by species like Gardnarella vaginalis, Mycoplasma hominis Ø BV increases vaginal inflammation and increases shedding of HIV into cervicovaginal fluid

46 SUMMARY Ø STI/RTI facilitate HIV transmission Ø Treatment of STI s/rti s reduce the concentration of HIV in semen and vaginal fluids Ø Treatment of some STI s may also reduce the concentration of HIV in plasma (e.g., HSV-2) Ø Reducing the concentration of HIV in genital fluids and plasma should reduce HIV transmission Ø Amazingly, population-targeted interventions in treating symptomatic and asymptomatic STI s/ RTI s have not shown an effect in reducing HIV incidence

47 CASE STUDY DISCUSSION

48 CASE STUDY Ø Ø Ø Ø Ø Ø Ø Ø Ø Scott, a 19-year-old who was visiting his cousin Matt at a local college campus decided to attend a party given by a graduate student Before leaving for the party, at 10:00 PM, Matt warned Scott to stick to punch or sodas and not to drink any alcoholic beverages He also advised him not to leave his drink unattended Scott promised and consumed a total of three glasses of fruit punch; He did not consume any alcohol At 3:00 AM when the party was winding down and Matt was ready to go home he was unable to locate his cousin Scott was found unconscious at about 3:45 AM lying in a fetal position; He was nude from the waist down and bleeding from his rectum There was also evidence of vomitus and bruise on his left cheek The police were called and Scott was rushed to the emergency room Two hours later, Matt was told that Scott was raped and did not want to see him or anyone else. From HU CRTP Case Study Bank

49 WHAT WOULD YOU DO?

50 CONSIDER. ØSensitivity and specificity of home HIV tests ØProper use and interpretation of results ØDetection of acute HIV infection by rapid tests ØIs the subject a candidate for npep?

51 REFERENCES Update: HIV Prophylaxis Following Non-Occupational Exposure, April Updated guidelines for antiretroviral post exposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV United States, new_guidelines_for_non_occupational_post_exposure_prophylaxis_in_new_york (video) Pre Exposure Prophylaxis for the Prevention of HIV Infection in the United States -2014: A Clinical Practice Guideline (US Public Health Service) HIV Post-Exposure Prophylaxis for Occupational and Non-occupational Exposure

52 QUESTIONS?

53 TEST YOUR KNOWLEDGE

54 Test Your Knowledge Question #5 A patient is started on npep and the baseline HIV test comes back showing the person is positive. The clinician should: A. Immediately stop the npep regimen B. Request a confirmatory HIV test C. Add an additional antiretroviral to the npep regimen D. Repeat the test using a rapid HIV test

55 Test Your Knowledge Question #6 Which of the following patient with HIV has the highest risk of infecting their partner? A. An elite controller B. A patient suppressed on a combination regimen C. A patient with acute HIV infection unaware of their status D. A patient who has been infected for about a year but is unaware of their status

56 Which regimen is preferred to npep? Test Your Knowledge Question #7 A. A triple nucleoside combination B. Dolutegravir, tenofovir, emtrictibine C. Atripla D. Kaletra/Combivir

57 TEST YOUR KNOWLEDGE QUESTION #8 A subject presents to the ER for testing suspecting they may have acute HIV infection. What single test would be most useful in determining this? A. A viral load (HIV RNA) B. A western blot C. A fourth-generation HIV test D. A home HIV test

58 Howard University HURB th Street, NW, 2 nd Floor Washington DC (Office) (Fax) As a Reminder: At the end of the Webinar, All participants are required to complete and return the CME Evaluation Survey. It may be scanned or ed back to: den_bailey@howard.edu or faxed to AETC Capitol Region Telehealth Training Center. (FAX # ) ATTN: Training Coordinator Please indicated in your or fax if you would like to receive CMEs.