PRE AND POST EXPOSURE PROPHYLAXIS IN HIV PREVENTION

Kimberly Woodhull, PharmD, AAHIVP

Objectives

Understand the current guidelines for occupational exposure prophylaxis

Select the appropriate drug regimen and duration of treatment for post exposure prophylaxis (PEP)

Understand the need for pre-exposure prophylaxis (PrEP)

Identify patients that are eligible for PrEP and recommend treatment

HIV Facts

In 2008, 2.7 million new HIV infections diagnosed worldwide

1.2 million people in US with HIV

21% unaware of their status

56,000 new HIV infections in US per year Men who have sex with men (MSM) over half of new

infections Women 27% of new infections

HIV patients will spend $600,000 for lifetime care

AIDS Facts

In 2009, estimated 34,247 people were diagnosed with AIDS

More than 594,500 people have died of AIDS since beginning of epidemic

~17,000 people died of AIDS in the US in 2009

Post Exposure Prophylaxis (PEP)

Percutaneous Occupational Exposures

In 2004, estimated 385,000 needlesticks/year

40-70% needlestick injuries unreported

Risk of Transmission HIV- 0.3% HBV-2-40% HCV-2.7-10%

PEP 80% effective

Case –Is JR Candidate for PEP? 28 yo nurse assistant at elementary

school

Stuck with needle while giving 3rd grader a diabetes shot before lunch

Parents refusing HIV testing

Is JR candidate for PEP?

After Needle Stick Injury

Decontamination Wash the area with soap and water Avoid squeezing or milking the wound Do not use caustic agents, such as bleach

Determine Risk Type of exposure Infection Status of Source

Decide on Treatment Gets Labs and Follow up in 3-6 months

Post Exposure Prophylaxis for the Healthcare Worker

Percutaneous injury (needlestick, cut)

OR

Contact of mucous membrane or nonintact skin

Blood Tissue Other body fluids

that are potentially infectious (cerebrospinal, semen or vaginal secretions)

Risks: With:

Assess Risk for HIV Infection

Type of exposure Less severe: solid needle or superficial injury More severe: large-bore hollow needle, deep

puncture, visible blood on device, needle used in patient’s artery or vein

Infection status of source Class 1: asymptomatic HIV infection or known

low viral load (<1,500 copies/mL) Class 2: symptomatic HIV, AIDS, acute

seroconversion, or known high viral load

Initiating PEP

Start within 72 hours

2-3 drug regimen based on risk

PEP should be given for 28 days, if tolerated

PEP for Percutaneous Injuries HIV + Source

Exposure Type Infection Status of SourceExposure Type Infection Status of

Source

HIV+, class 1 HIV+, class 2

Less severe Recommend basic 2-drug PEP

Recommend expanded ≥3-drug PEP

More severe Recommend expanded 3-drug PEP

Recommend expanded ≥3-drug PEP

PEP for Percutaneous Injuries Unknown Source

Exposure Type Infection Status of SourceExposure Type Infection Status of

Source

Unknown HIV status*

Unknown source

Less severe Generally, no PEP warranted; consider basic 2-drug PEP if source has HIV risk factors

Generally, no PEP warranted; consider basic 2-drug PEP if exposure to HIV-infected persons is likely

More severe As above As above*If PEP started and source later determined to be HIV negative, PEP should be discontinued.

Case –Is JR Candidate for PEP? Exposure-Less severe

Infection source status-Unknown

Time –Within 72 hours

Treat?

However….

ER provider recommended starting PEP for 28 days: Zidovudine/lamivudine (Combivir®) Indinavir (Crixivan®) or Nevirapine

(Viramune®)

Guidelines for Treatment

Basic 2 Drug Regimens: Preferred:

ZDV + 3TC or FTC TDF + 3TC or FTC

Alternative: d4T + 3TC or FTC ddI + 3TC or FTC

Expanded ≥3 drug: Preferred:

LPV/RTV (Kaletra) + Alternative:

ATV* ± RTV FPV ± RTV IDV** ± RTV SQV + RTV NFV*** EFV***

* If ATV is coadmnistered with TDF, RTV must be included in the PEP regimen.** Avoid in late pregnancy. *** Avoid in pregnancy.

IF PEP: Recommended Regimen

PEP Questions

Consult Guidelines Available at

http://www.aidsinfo.nih.gov/guidelines

National Clinician’s Postexposure Prophylaxis Hotline (PEPline) Telephone consultation service:

1-888-448-4911 9 am-2 am EST

JR Conclusion

JR opted not to take treatment

Child tested; negative

Recap PEP

Determine severity of risk

Source of infection

Initiate treatment within 72 hours

Treat with Truvada +/- Kaletra

Treat for 28 days

Pre Exposure Prophylaxis (PrEP)

Pre-Exposure Prophylaxis for HIV Prevention Antiretrovirals in HIV patients restores health

and may decrease transmission of virus to uninfected partners

HIV pill taken daily or gel applied to vagina Tenofovir (TDF) and Truvada (FTC-TDF)

Reduce risk of HIV infection Rationale based on:

Prevention of mother to child transmission Post exposure prophylaxis Animal Studies

PREP Trials Worldwide

Study 1: FHI West Africa Phase 2, randomized, double-blind, placebo-

controlled June 2004 to March 2006 Enrolled in 3 sites: Ghada, Camerron, and Nigeria 936 HIV-negative women at high risk of HIV infection

469 received TDF 467 received placebo

Safety endpoints measured by Serum creatinine >2.0 mg/dl Phosphorus <1.5 mg/dl Alanine aminotranferase elevations >170 U/I

Efficacy measured by infection of HIV-1 or HIV-2

Study 2: Preexposure Prophylaxis Initiative (iPrEx) Phase 3, randomized, double-blind,

placebo-controlled 11 sites in six countries July 2007-December 2009

3,324 person-years 2,499 HIV negative men or transgender

women who have sex with men 1,251 given FTC-TDF 1,248 given placebo

Study 3: CAPRISA 004

Phase II, double-blind, randomized, placebo-controlled

May 2007-March 2010 1,341 women years

889 women at high risk of HIV through intercourse 445 tenofovir gel 444 placebo gel

Efficacy Results

Data from FH1 West Africa

TDF Placebo Incidence Rate

Person-Years of

Follow-Up

232.6 241.3

HIV infections/10

0 person-years

0.86 2.48 0.35

Reduction in Risk for HIV Acquisition in iPrEX Trial

FTC-TDF(events)

Placebo(events)

Hazard Ratio

HIV Infection 36 64 0.56 (0.37-0.85)

Pill Use <90%

28 34 0.79 (0.48-1.31)

Pill Use ≥90%

8 30 0.27 (0.12-0.59)

Effectiveness of tenofovir gel in HIV Prevention in CAPRISA 004

HIV Incidence/100 Women Years

Tenofovir gel(95% CI)

Placebo gel(95% CI)

Incidence Rate Ratio

HIV total 5.6 9.1 0.61

Gel Use >80% 4.2 9.3 0.46

Gel Use <50% 6.2 8.6 0.72

Results from TDF2 and Partners PrEP TDF2 Study –Reduced risk by 63%

Separate analysis showed 78% risk reduction

Partners PrEP 62% with Tenofovir (p=0.0003) 73% with Truvada (p<0.0001)

Conclusions

PrEP effective in HIV prevention

Adherence is critical

Used in high risk populations

PrEP should be used in combination with other prevention methods

Questions

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2011.

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