Keith W. Crawford, R.Ph., Ph.D. HIV Faculty Expert
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 0.5 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 Funded by Health Resources Services Administration (HRSA) Grant #H4AHA24081
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 Denise Bailey, MEd Marjorie Douglas-Johnson, BA Kwame Frimpong Speaker: The following speaker has nothing to disclose in relation to this activity: Keith W. Crawford, R Ph, PhD
Intended Audience: Low volume clinicians (i.e. those with fewer than 25 patients in their case load who are HIV positive): 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. Your presence on the call must be acknowledged at the start of each session. Please log in for the session then announce your name loudly and clearly at the beginning of the session. You will not be able to receive CME credit if you leave the session early. At the end of the Webinar our Training Coordinator will email a CME Evaluation Survey. All participants are required to complete and return the CME Evaluation Survey at the end of each session. It may be scanned and emailed back to mdouglas@howard.edu, or faxed to: AETC-Capitol Region Telehealth Project (FAX#: 202.667.1382) ATTN: Training Coordinator. Please indicate in your email or FAX if you would like to receive CME credit.
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
Which statement is correct? A. Population-based treatment of symptomatic and asymptomatic urethritis has been shown to reduce HIV incidence B. An additional advantage of treating bacterial vaginosis is that it increases CD4+ cell count in HIV patients not on antirtroviral therapy C. Successful treatment of most STI's will result in a reduction of HIV in semen and vaginal fluid D. HSV-2 infection increases the acquisition of HIV from female to male but not from male to female E. All statements are correct
The most effective agent as a topical microbicide is: A. Topical AZT (zidovudine creme) B. A topical gel containing the spermicide nonoxynol-9 C. Tenofovir gel D. Carraguard gel E. They are all equally effective
Upon completion of this webinar, participating providers will have the enhanced ability to: Discuss CDC guidelines for non-occupational HIV post-exposure prophylaxis (n-pep) Discuss timing of Post Exposure Prophylaxis treatment initiation Describe post-exposure prophylaxis therapy and side effects State challenges associated with Post Exposure Prophylaxis Explain transmission risks for various n-pep exposures Understand the dynamics of HIV transmission and early infections and select tests likely to be most accurate based on the subject s stage of infection Assess the level of risk of transmission for a patient presenting for npep 10
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 young 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
Receptive or insertive vaginal or anal sex Sharing needles for drug-use Injuries with exposure to blood or other high-risk fluids from a person known to be HIV+ or of unknown status npep is NOT indicated for low-risk exposures!
Tenofovir/Emtricitibine Plus Raltegravir or Dolutegravir Boosted protease inhibitor Atazanavir (300/100) or Darunavir (800/100) Treatment should be initiated ideally with 36 hours of exposure, certainly with 72 hours, and continued for 28 days
Perform baseline testing Perform testing of the source (if possible) Test subject at baseline, week four postexposure and week 12
Clinical chemistries for monitoring patients on ART at baseline, week 2 and 4 post-exposure -liver enzymes, BUN, creatinine, CBC Test for other STI s at baseline - gonorrhea/chlamydia NAAT - syphilis RPR HCV/HBV Pregnancy test
Male Circumcision as a Strategy for Reducing HIV Transmission Risk
The foreskin contains a mucosal surface on the penis This mucosal surface can be a gateway for pathogens, particularly sexually-transmitted ones, into the body Dendritic cells and other APC s maintain surveillance for pathogens that breach the foreskin mucosal surface Dendritic cells that encounter HIV can carry the virus almost in a Trojan Horse style to infect T lymphocytes in lymphoid tissues Three RCT demonstrate efficacy of male circumcision in reducing risk of HIV transmission by 50-60%
Figure 2 Source: The Lancet 2007; 369:657-666 (DOI:10.1016/S0140-6736(07)60313-4) Terms and Conditions
Figure 2 Source: The Lancet 2007; 369:643-656 (DOI:10.1016/S0140-6736(07)60312-2) Terms and Conditions
TABLE 1. Voluntary medical male circumcisions (VMMCs) performed by CDC-supported programs, by country and fiscal year, 2010 2013 Country No. of VMMCs 2010 2011 2012 Total Botswana 8,590 8,590 Kenya* 104,131 166,310 116,311 386,752 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 80,701 100,095 Tanzania 1,519 50,325 49,756 101,600 Uganda 9,052 57,132 139,628 205,812 Zambia 13,368 33,841 58,309 105,518 Total 137,096 347,724 535,604 1,020,424 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. * 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 2012. South Africa's data are reported from January December for 2010 2012. Tanzania's data for 2010 2012 are from APR reports and Tanzania's national database.
HSV-2? Chlamydia? Gonorrhea? Trichomonas vaginalis? High-risk and low-risk HPV genotypes!
STI 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 Genital Ulcer Disease (GUD) caused by STI s (HSV- 1,2, syphilis) compromise the integrity of the mucosal barrier and facilitate HIV transmission
STI s (e.g. gonorrhea) can increase the amount of HIV in semen and vaginal fluids up to 10x increasing exposure to the partner Reproductive Tract Infections (RTI; bacterial vaginosis, Trichomonas) increase HIV in vaginal fluids and risk of transmission STI s and RTI s increase the risk of HIV transmission from seropositive individuals and also HIV acquisition by a seronegative individual
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 Gonorrhoea was associated with the greatest concentration of HIV-1 in semen 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 = 0.0001]) Cohen et al., Lancet,2007,349(9069):1868-73
A causative agent of genital ulcer disease HSV-2 is suspected to be a major driver of the HIV epidemic in Africa
The Effect of Valacyclovir on Postpartum Plasma (A) and Breast Milk (B) Human Immunodeficiency Virus Type 1 (HIV-1) RNA Levels Drake A L et al. J Infect Dis. 2012;205:366-375
Effect of Valacyclovir Treatment on HIV RNA Levels in Rectum and Plasma in Co-Infected MSM s (in Co-Infected B) HIV-1 Levels between Treatment Arms, by Individual Participant 2007 by the Infectious Diseases Society of America Zuckerman R A et al. J Infect Dis. 2007;196:1500-1508
Lactobacillus sp. predominate in the vaginal normal flora Bacterial vaginosis is characterized by alterations in the vaginal microbiome and colonization by species like Gardnarella vaginalis, Mycoplasma hominis BV increases vaginal inflammation and increases shedding of HIV into cervicovaginal fluid
Incidence of HIV-1 Transmission to Men, by the Vaginal Flora Category of their Female HIV-1 Infected Partner Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, et al. (2012) Bacterial Vaginosis Associated with Increased Risk of Female-to- Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples. PLoS Med 9(6): e1001251. doi:10.1371/journal.pmed.1001251 http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001251
STI/RTI facilitate HIV transmission Treatment of STI s/rti s reduce the concentration of HIV in semen and vaginal fluids Treatment of some STI s may also reduce the concentration of HIV in plasma (e.g. HSV-2) Reducing the concentration of HIV in genital fluids and plasma should reduce HIV transmission Amazingly, population-targeted interventions in treating symptomatic and asymtomatic STI s/rti s have not shown an effect in reducing HIV incidence
Topical Microbicides
Topical microbicides are formulations (gels, creams, devices) that are applied/inserted vaginally or rectally to prevent infections from agents like HIV. They are designed to protect the receptive partner. They may: Kill or inactivate the pathogen (e.g. detergents) Create a barrier preventing the pathogen crossing the mucosa Pharmacologically target the pathogen preventing replication in or spread from mucosal tissues
TRIAL MICROBICIDE N COUNTRIES EFFECT Abdool Karim 2011 BufferGel 1546 Malawi, South Africa, United States, Zambia, Zimbabwe RR 1.05, 95% CI 0.73 to 1.52 Skoler-Karpoff 2008 Carraguard 6202 South Africa RR 0.89, 95% CI 0.71 to 1.11 Halpern 2008, Van Damme 2008 CS 3069 Benin, India, Nigeria RR 1.20, 95% CI 0.74 to 1.95 Abdool Karim 2011, McCormack 2010 PRO 2000 8191 Malawi, South Africa, Tanzania, Uganda, United States, Zambia, Zimbabwe RR 0.93, 95% CI 0.77 to 1.14 Feldblum 2008, Peterson 2007 SAVVY (C31G) 4295 Ghana, Nigeria RR 1.38, 95% CI 0.79 to 2.41 Abdool Karim 2010 TDF 889 South Africa, Uganda, Zimbabwe RR 0.63, 95% CI 0.43 to 0.93
# HIV infections / women years Tenofovir Placebo Overall effectiveness of tenofovir gel HIV 38 / 60 / 660.7 889 endpoints 680.6 N HIV incidence Tenofovir gel (95% CI) 5.6 (4.0, 7.7) Placebo gel (95% CI) 9.1 (6.9, 11.7) Incidence Rate Ratio Effectiveness 95% Confidenc e Interval p- value 0.61 39% 6, 60 0.017 HIV endpoints by levels of adherence^ High adherers 25 / (>80% gel 11 / 259.2 269.4 adherence) Intermediate adherers (50-80% adherence) Low adherers (<50% gel adherence) 10 / 159.8 16 / 258.5 10 / 99.7 25 / 290.6 336 181 367 4.2 (2.1, 7.6) 6.3 (3.0, 11.5) 6.2 (3.5, 10.1) 9.3 (6.0, 13.7) 10.0 (4.8, 18.4) 8.6 (5.6, 12.7) 0.46 54% 4, 80 0.025 0.62 38% -67, 77 0.343 0.72 28% -40, 64 0.303
# HIV infections /women years T Tenofovir Placebo N Tenofovir gel (95% CI) HIV incidence Overall effectiveness of tenofovir gel HIV endpoints 38 / 680.6 60 / 660.7 889 5.6 (4.0, 7.7) Placebo gel (95% CI) 9.1 (6.9, 11.7) Incidence Rate Ratio Effectivenes s 95% Confidenc e Interval p- value 0.61 39% 6, 60 0.017 Effectiveness of tenofovir gel by study exit HSV-2 status HSV-2 positive 29 / 397.7 46 / 410.7 541 7.3 (4.9, 10.5) 11.2 (8.2, 14.9) 0.65 35% -6, 61 0.070 HSV-2 negative 9 / 272.8 14 / 248.0 339 3.3 ( 1.5, 6.3) 5.6 (3.1, 9.5) 0.58 42% -45, 78 0.209
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 young 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
Sensitivity and specificity of home HIV tests Proper use and interpretation of results Detection of acute HIV infection by rapid tests Is the subject a candidate for npep?
UPDATE: HIV Prophylaxis Following Non-Occupational Exposure http://www.hivguidelines.org/clinical-guidelines/post-exposure-prophylaxis/hiv-prophylaxis-followingnon-occupational-exposure/ http://www.prn.org/index.php/transmission/article/new_guidelines_for_non_occupa tional_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) http://www.cdc.gov/hiv/pdf/guidelines/prepguidelines2014.pdf HIV Post-Exposure Prophylaxis for Occupational and Non-occupational Exposure http://www.ceiconnect.org/p43148073/?launcher=false&fcscontent=true&pbmode= normal
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
Which statement is correct? A. Population-based treatment of symptomatic and asymptomatic urethritis has been shown to reduce HIV incidence B. An additional advantage of treating bacterial vaginosis is that it increases CD4+ cell count in HIV patients not on antirtroviral therapy C. Successful treatment of most STI's will result in a reduction of HIV in semen and vaginal fluid D. HSV-2 infection increases the acquisition of HIV from female to male but not from male to female E. All statements are correct
The most effective agent as a topical microbicide is: A. Topical AZT (zidovudine creme) B. A topical gel containing the spermicide nonoxynol-9 C. Tenofovir gel D. Carraguard gel E. They are all equally effective
Howard University HURB 1 1840 7 th Street NW, 2 nd Floor Washington, DC 20001 202-865-8146 (Office) 202-667-1382 (Fax) As a Reminder: At the end of the Webinar, participants are required to complete and return the CME Evaluation Survey. It may be scanned and emailed back to mdouglas@howard.edu, or faxed to: AETC-Capitol Region Telehealth Project (FAX#: 202.667.1382) ATTN: Training Coordinator. Please indicate in your email or FAX if you would like to receive CME credit. www.capitolregiontelehealth.org www.aetcnmc.org