Workshop 4: HIV/AIDS em crian ças e adolescentes ...Needlestick Injury: When should ARVs be given?...

Workshop 4:

HIV/AIDS em crianHIV/AIDS em criançças e adolescentesas e adolescentesManagement of Pediatric and Management of Pediatric and Adolescent HIV InfectionAdolescent HIV Infection

Allison Agwu, M.D., ScMAllison Agwu, M.D., ScM

ANDAND

Deborah Persaud, M.D.Deborah Persaud, M.D.

Pediatric Infectious DiseasesPediatric Infectious Diseases

Johns Hopkins Medical InstitutionsJohns Hopkins Medical Institutions

Rio de Janeiro, BrasilRio de Janeiro, Brasil

April 11, 2012April 11, 2012 11

Financial DisclosuresFinancial Disclosures

�� NoneNone

22

ObjectivesObjectives

�� To discuss common dilemmas faced by To discuss common dilemmas faced by primary care providers with respect to HIV primary care providers with respect to HIV prevention in neonates and youthprevention in neonates and youth

�� To examine criterion for diagnosis of HIV To examine criterion for diagnosis of HIV infection in infantsinfection in infants

�� To understand recommendations for nonTo understand recommendations for non--occupational HIV postoccupational HIV post--exposure prophylaxisexposure prophylaxis

33

OutlineOutline

�� CaseCase--based, interactivebased, interactive

�� Review of the evidence supporting Review of the evidence supporting

actions taken in each caseactions taken in each case

HIVHIV--infection and infection and PregnancyPregnancy

�� 2/3 of HIV2/3 of HIV--infected women are of infected women are of

childchild--bearing age (between ages bearing age (between ages

1313--44 y/o)44 y/o)

�� HIV+ women are just as likely to HIV+ women are just as likely to

become pregnantbecome pregnant as HIVas HIV--uninfected uninfected

women women

�� They are no more likely to They are no more likely to

terminate a pregnancy.terminate a pregnancy.

�� 12% conceive after HIV diagnosis.12% conceive after HIV diagnosis.

�� Another 10% had their infection Another 10% had their infection

diagnosed during pregnancydiagnosed during pregnancy

Kirshenbaum SB, et al. Perspectives on Sexual & Reproductive Health, 2004; 36(3); CDC.gov

55

Case #1: Prophylaxis of Neonate Born Case #1: Prophylaxis of Neonate Born to an HIVto an HIV--Infected MotherInfected Mother

�� 2 hour old neonate born to a 422 hour old neonate born to a 42--yearyear-- old mother old mother (G4P3003) with known history of HIV infection and (G4P3003) with known history of HIV infection and polysubstance abuse (cocaine/heroin)polysubstance abuse (cocaine/heroin)–– HIV infection diagnosed in previous pregnancyHIV infection diagnosed in previous pregnancy

WHAT ADDITIONAL INFORMATION WOULD YOU NEED TO ASSIST WITH WHAT ADDITIONAL INFORMATION WOULD YOU NEED TO ASSIST WITH

RECOMMENDATIONS FOR MANAGEMENT OF THE INFANT?RECOMMENDATIONS FOR MANAGEMENT OF THE INFANT?

66

Case #1: Recommendations for Prophylaxis of Neonate Case #1: Recommendations for Prophylaxis of Neonate Born to an HIVBorn to an HIV--Infected MotherInfected Mother

�� Antiretroviral Treatment Status Antiretroviral Treatment Status

�� Viral LoadViral Load

�� CD4 CountsCD4 Counts

�� Maternal screen for sexually transmitted diseases Maternal screen for sexually transmitted diseases

�� Mode of Delivery Mode of Delivery

�� Complications of Delivery Complications of Delivery �� Intrapartum ARVsIntrapartum ARVs

�� Neonatal statusNeonatal status

77

Case #1: Recommendations for Prophylaxis of Neonate Case #1: Recommendations for Prophylaxis of Neonate Born to an HIVBorn to an HIV--Infected MotherInfected Mother

�� Antiretroviral Treatment Status Antiretroviral Treatment Status (None received) (None received)

�� Viral Load Viral Load (unknown)(unknown)

�� CD4 Counts CD4 Counts (unknown)(unknown)

�� Maternal screen for sexually transmitted diseases Maternal screen for sexually transmitted diseases (unknown)(unknown)

�� Mode of Delivery Mode of Delivery (vaginal; spontaneous)(vaginal; spontaneous)

�� Complications of Delivery Complications of Delivery [Preterm (32 5/7 weeks);prolonged [Preterm (32 5/7 weeks);prolonged rupture of membranes (62 hours)]rupture of membranes (62 hours)]

�� Intrapartum ARVsIntrapartum ARVs

–– initially started on IV AZT due to active laborinitially started on IV AZT due to active labor

–– however, when labor did not progress; mother was started however, when labor did not progress; mother was started on HAART with EFV/TDF/FTCon HAART with EFV/TDF/FTC

–– Labor then occurred precipitously with no opportunity for IV Labor then occurred precipitously with no opportunity for IV AZTAZT

�� Neonatal status Neonatal status ((Birth Wt 1830g), APGARS 9/9; well appearing; Birth Wt 1830g), APGARS 9/9; well appearing; unremarkable exam unremarkable exam

88

What do you do?What do you do?

a) a) Do nothing as baby is outside of the window Do nothing as baby is outside of the window

where any intervention will be helpful in where any intervention will be helpful in

preventing transmissionpreventing transmission

b) Administer antiretroviral drugs b) Administer antiretroviral drugs

c) If so, which antiretroviral drugsc) If so, which antiretroviral drugs

d) Start antiretrovirals when the baby is seen in d) Start antiretrovirals when the baby is seen in

the office at six weeks for followthe office at six weeks for follow--upup

99

Answer: Initiate ARV Prophylaxis to Answer: Initiate ARV Prophylaxis to

Infant Immediately: Infant Immediately: Risk of Perinatal Risk of Perinatal

TransmissionTransmission is HIGH!! is HIGH!!

9-13%

ARV in Labor

ARV (antepartum/intrapartum/postpartum)

<2%Wade,et al. 1998 NEJM 339;1409-14Guay, et al. 1999 Lancet 354;795-802Fiscus, et al. 2002 Ped Inf Dis J 21;664-668Moodley, et al. 2003 JID 167;725-735 Courtesy (P. Garcia)

Transm

ission

Rate

Risk Assessment and Selection of Risk Assessment and Selection of

Neonatal Antiretroviral ProphylaxisNeonatal Antiretroviral Prophylaxis

1111

What was motherWhat was mother’’s CD4 & viral load (VL)? s CD4 & viral load (VL)?

•• Advanced immunosuppression , higher VL Advanced immunosuppression , higher VL �� higher likelihood of transmissionhigher likelihood of transmission

When was mother diagnosed? Acute vs. chronic?When was mother diagnosed? Acute vs. chronic? �� Acute infection higher likelihood Acute infection higher likelihood

Is mother on an antiretroviral regimen? Is mother on an antiretroviral regimen?

•• What was the regimen?What was the regimen?

•• If yes, have there been concerns about adherence?If yes, have there been concerns about adherence?

•• Any noted resistance mutations?Any noted resistance mutations?

What is motherWhat is mother’’s most recent VL(> or < 1000 copies/ml)?s most recent VL(> or < 1000 copies/ml)?

What was the mode of delivery? What was the mode of delivery?

–– If CIf C--section: reasons for Csection: reasons for C--sectionsection

–– Planned repeat C/S or elevated VL (>1000 copies/mL)Planned repeat C/S or elevated VL (>1000 copies/mL)

–– Vaginal delivery: duration of ROM? (> or < 4 hours)Vaginal delivery: duration of ROM? (> or < 4 hours)

Any obstetric complications?Any obstetric complications?

•• abruption, laceration, use of scalp electrodesabruption, laceration, use of scalp electrodes

Any maternal coAny maternal co--infections?infections?

•• ulcerative sexually transmitted diseasesulcerative sexually transmitted diseases

Viral load and transmissionViral load and transmission

1212

Dickover RE et al. JAMA. 1996;275:599-605

Nielsen-Saines et al. CROI 2011

Preventing Intrapartum Transmission Preventing Intrapartum Transmission in Late Presenters: Evidencein Late Presenters: Evidence

Note: moms only received AZT, no HAART; Infants: no extreme prematurity, able to tolerate po

Nielsen-Saines et al. CROI 2011

Preventing Intrapartum Transmission in Late Preventing Intrapartum Transmission in Late Presenters: EvidencePresenters: Evidence

Selection of Neonatal Antiretroviral Selection of Neonatal Antiretroviral Prophylactic Regimen (Maternal HAART)Prophylactic Regimen (Maternal HAART)

Maternal HAART

VL < 1000 VL>1000- <10,000

ZDV x 6 weeks ZDV x 6 weeks +

Single Dose of Nevirapine+

3TC for one week

VL>10,000

VaginalC/S Vaginal or C/S

ID consult for infants assessed as requiring more than AZT for prophylaxis (Hopkins guidelines adapted from DHHS guidelines 2011)

1515

Infants of Untreated HIV Infected MothersInfants of Untreated HIV Infected Mothers

HIV+ Untreated

Regardless of Mode of Delivery

Maternal CD4 or Viral load

ZDV x 6 weeks

Nevirapine

3TC*

1616

*Refer to DHHS Pediatric Guidelines, Sept 2011

Management of the Neonate Management of the Neonate (Case #1): 2 wks old now(Case #1): 2 wks old now

�� The infant is now 2 weeks old The infant is now 2 weeks old

�� Gaining weight well, physical exam is Gaining weight well, physical exam is unremarkable unremarkable

�� Medications: AZT, completed one week Medications: AZT, completed one week of 3TC, and received a single dose of of 3TC, and received a single dose of nevirapinenevirapine

�� HIV antibody positive at birthHIV antibody positive at birth

BASED ON THIS INFORMATION, IS THE BABY INFECTED?BASED ON THIS INFORMATION, IS THE BABY INFECTED?

1717

Is this infant infected?Is this infant infected?

a)a) YesYes

b)b) NoNo

c)c) Indeterminate (unknown)Indeterminate (unknown)

1818

Determination of HIV Infection in Determination of HIV Infection in the Neonate (Case #1): 7 wks old the Neonate (Case #1): 7 wks old

�� The infant is now 7 weeks old The infant is now 7 weeks old

�� Gaining weight well, physical exam is Gaining weight well, physical exam is unremarkable unremarkable

WHAT QUESTIONS DO YOU HAVE TO HELP WHAT QUESTIONS DO YOU HAVE TO HELP DETERMINE INFECTION STATUS FOR THIS DETERMINE INFECTION STATUS FOR THIS

INFANT?INFANT?

1919

Determination of HIV Infection Determination of HIV Infection in the Neonate? in the Neonate?

�� How do you determine this?How do you determine this?

�� What testing is needed?What testing is needed?

�� When would you perform testing?When would you perform testing?

�� What is the definition of What is the definition of

infected/uninfected?infected/uninfected?

2020

HIV Testing in Exposed InfantsHIV Testing in Exposed Infants

� Appropriate test: HIV DNA or RNA PCR.– Perform on infant sample: umbilical cord blood is inappropriate

�� Virologic diagnostic testing is recommended in Virologic diagnostic testing is recommended in infants with known perinatal HIV exposure at infants with known perinatal HIV exposure at ages 14ages 14––21 days, 121 days, 1––2 months, and 42 months, and 4––6 months 6 months of ageof age� Some experts recommend 48hr testing (high risk)

� PCR Sensitivity at birth 30-40%, at 14-21 days >90%

http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf2121

How is infection ruled out?How is infection ruled out?

� Definitively HIV uninfected: negative tests at >1 month and ≥4 months

� Confirmation HIV ab at 12-18 months to document seroreversion

Assumptions: no premastication, Assumptions: no premastication, breastfeeding, or other potential exposuresbreastfeeding, or other potential exposures

http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf2222

Case 1: Timeline of testing and ARVs for PMTCTCase 1: Timeline of testing and ARVs for PMTCT

2323

Day 0Birth

Day 1 Day 5 Day 7 Day 15

?QNS

?QNS

+Result received at DOL 15

Intrapartum AZTInfant AZT/NVP/3TC

AZT

+Result at DOL 36

Positive by HIV DNA PCR

Viral load assessmentsViral load assessments

2424

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

7 15 30 60 90 120 150

HIV-1 RNA

Ultrasensitive

HIV RNA Copies/mL

Days of Life

AZT off

Is this infant infected?Is this infant infected?

a)a) YesYes

b)b) NoNo

c)c) Indeterminate (unknown)Indeterminate (unknown)

2525

Case 1: Interpreting the resultsCase 1: Interpreting the results

� HIV ab + == mom� HIV DNA PCR positive at days 9 and day 14� Antiretrovirals may suppress the viral replication �RNA being undetectable

� AZT stopped and viral load rebounded to 8,000 copies/mL

INFECTED

http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf

2626

Case 1: ManagementCase 1: Management

� Consult ID� Discontinue AZT monotherapy� Initiate bactrim prophylaxis� Initiate HAART as soon as possible� Close monitoring (baseline CD4, viral load, resistance testing, monitoring labs)

� Childhood immunizations

http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf

2727

Diagnosing HIV neonate/older children in Diagnosing HIV neonate/older children in

the era of enhanced PMTCTthe era of enhanced PMTCT

�� Implications of full ARV regimens on Implications of full ARV regimens on

ability to diagnose infection in ability to diagnose infection in

infants/neonatesinfants/neonates

�� Dilemmas and challengesDilemmas and challenges

�� Implications of early neonatal therapyImplications of early neonatal therapy

2828

When to start? What to start? When to start? What to start? (Case 1): Infected infant(Case 1): Infected infant

�� Initial CD4 3200 cells/mmInitial CD4 3200 cells/mm33

�� CD4%= 28.5CD4%= 28.5

�� VL= 8000 copies/mLVL= 8000 copies/mL

�� Physical exam: unremarkablePhysical exam: unremarkable

2929


A)A) Patient does not meet criteria for Patient does not meet criteria for

treatment would watch and waittreatment would watch and wait

B)B) There are no available drugs to treat There are no available drugs to treat

infants this young, therefore would infants this young, therefore would

defer until olderdefer until older

C)C) Start therapy with AZTStart therapy with AZT

D)D) Start HAART with 2 NRTIs and a PI or Start HAART with 2 NRTIs and a PI or

NNRTINNRTI3030

When to Start?When to Start?

�� All infants <12 months of age All infants <12 months of age

regardless of CD4 or viral load levelregardless of CD4 or viral load level

DHHS guidelines, 2010


�� Children age Children age ≥≥1 year:1 year:

�� AIDS or significant symptoms (Clinical Category C AIDS or significant symptoms (Clinical Category C

or most Clinical Category B conditions), regardless or most Clinical Category B conditions), regardless

of CD4 or HIV RNA of CD4 or HIV RNA

�� Who have met the ageWho have met the age--related CD4 threshold for related CD4 threshold for

initiating treatment initiating treatment

�� CD4 <25% for children age 1 to <5 years CD4 <25% for children age 1 to <5 years

�� CD4 <500 cells/mmCD4 <500 cells/mm33 for children age for children age ≥≥5 years5 years

�� Regardless of symptoms or plasma HIV RNA Regardless of symptoms or plasma HIV RNA

level. level.



�� Children age Children age ≥≥1 year:1 year:

�� Who are asymptomatic or have mild symptomsWho are asymptomatic or have mild symptoms

�� have CD4 have CD4 ≥≥25% for children age 1 to <5 25% for children age 1 to <5

yearsyears

�� ≥≥500 cells/mm500 cells/mm33 for children age for children age ≥≥5 years5 years

�� andand have plasma HIV RNA have plasma HIV RNA ≥≥100,000 100,000

copies/mL. copies/mL.


When to consider delaying therapy?When to consider delaying therapy?

�� Treatment may be Treatment may be considered or considered or

deferred deferred for children age for children age ≥≥1 year 1 year

who:who:

–– are asymptomatic or have mild are asymptomatic or have mild

symptoms symptoms

–– and who have CD4 and who have CD4 ≥≥25% for children 25% for children

age 1 to <5 years and age 1 to <5 years and ≥≥500 cells/mm500 cells/mm33

for children age for children age ≥≥5 years 5 years

–– and have plasma HIV RNA and have plasma HIV RNA <100,000<100,000copies/mL copies/mL 3434

ARVARV--nanaïïve HIVve HIV--Infected Infants <12 months Infected Infants <12 months

�� Children with HIV Early Children with HIV Early Antiretroviral Therapy Antiretroviral Therapy [CHER] study:[CHER] study:�� South African clinical trial: South African clinical trial:

initiation of HAART prior to initiation of HAART prior to

age 12 weeks in age 12 weeks in

asymptomatic infants with asymptomatic infants with

CD4 >25% vs. delayed CD4 >25% vs. delayed

HAARTHAART

�� 75% 75% ↓↓ in early mortality in early mortality

found with early initiationfound with early initiation

�� 20/125 (16%) in the 20/125 (16%) in the

deferreddeferred--therapy group died therapy group died

vs. 10/252 (4%) in the earlyvs. 10/252 (4%) in the early--

therapy group, P<0.001therapy group, P<0.001Violari et al. NEJM 2008;359:2233-44.


A)A) Restart therapy with AZTRestart therapy with AZT

B)B) Patient does not meet criteria for Patient does not meet criteria for

treatment would watch and waittreatment would watch and wait

C)C) There are no available drugs to treat There are no available drugs to treat



D)D) Start HAART with 2 NRTIs and a PI or Start HAART with 2 NRTIs and a PI or

NNRTINNRTI3636

What to Start?What to Start?

�� PI/NNRTI + 2 NRTIsPI/NNRTI + 2 NRTIs

�� Preferred: lopinavir/ritonavirPreferred: lopinavir/ritonavir

�� Alternative regimen NVP (resourceAlternative regimen NVP (resource--limited settings limited settings

with no prior NVP exposure)with no prior NVP exposure)

�� Lopinavir/ritonavir for infants: Lopinavir/ritonavir for infants:

�� Cannot be given before 14 days of age and Cannot be given before 14 days of age and

postmenstrual age of 42 weekspostmenstrual age of 42 weeks

��Risk of accumulation of ETOH and propylene glycol Risk of accumulation of ETOH and propylene glycol

�� Leads to: cardiac toxicityLeads to: cardiac toxicity, lactic acidosis, acute renal failure, , lactic acidosis, acute renal failure,

CNS depression, and respiratory complications CNS depression, and respiratory complications

DHHS guidelines; www.FDA.gov

http://neuromonitoring.files.wordpress.com/2011/08/needlestick.jpg

3838

Case #2: On the playgroundCase #2: On the playground

�� 8 year old playing in a 8 year old playing in a

parkpark

�� Stuck by a syringe Stuck by a syringe

with needle attachedwith needle attached

�� The family has not The family has not

brought the needle inbrought the needle in

3939

4040

ADDITIONAL QUESTIONS?

WHAT SHOULD YOU DO?



�� Any irrigation or cleaning?Any irrigation or cleaning?

�� Immunization status of patient? Immunization status of patient?

–– (tetanus, Hep B, HBIG)(tetanus, Hep B, HBIG)

�� Characteristics of the wound?Characteristics of the wound?

�� Size of needle (gauge/bore)? Size of needle (gauge/bore)?

�� Blood in hub?Blood in hub?

�� Blood on skin? Blood on skin?

4141

The needlestick: First stepsThe needlestick: First steps

�� Irrigation/cleaningIrrigation/cleaning

�� Assess woundAssess wound

�� Assess immunization status and immunize (tetanus, Hep Assess immunization status and immunize (tetanus, Hep

B, HBIG)B, HBIG)

�� Testing (Hep B, C, HIV)Testing (Hep B, C, HIV)

�� Assess need for antiretrovirals Assess need for antiretrovirals

–– if exposure and risk deemed high (size of needle, if exposure and risk deemed high (size of needle,

blood in hub, on skinblood in hub, on skin))

Landovitz et al. NEJM 2009; 361: 1768-754242

PEP (PostPEP (Post--exposure prophylaxis) exposure prophylaxis)

Guidelines: Needle Stick Guidelines: Needle Stick

�� Overall risk of HIV transmission through Overall risk of HIV transmission through

percutaneous inoculation = 0.3% (95% CI 0.2 to percutaneous inoculation = 0.3% (95% CI 0.2 to

0.5) 0.5)

�� Estimated risk of transmission associated with Estimated risk of transmission associated with

sharing needles for injectionsharing needles for injection--drug use is drug use is

approximately 0.67% per needleapproximately 0.67% per needle--sharing contact.sharing contact.


Needlestick Injury: When should ARVs be given?Needlestick Injury: When should ARVs be given?

�� Features associated with Features associated with ↑↑ rrate of transmission:ate of transmission:

–– Deep needlestick, and visible blood on the surface of the Deep needlestick, and visible blood on the surface of the

instrument.instrument.

–– Advanced HIV disease in the source patientAdvanced HIV disease in the source patient

–– Clinical judgment is required to assess the likelihood that the Clinical judgment is required to assess the likelihood that the

inoculum is sufficient to pose a credible threat of transmissioninoculum is sufficient to pose a credible threat of transmission�� many clinicians use a puncture that draws blood as a general thmany clinicians use a puncture that draws blood as a general threshold. reshold.

�� Initiate as soon as possibleInitiate as soon as possible

�� Ideally <36 hoursIdeally <36 hours

�� Treat x 28 daysTreat x 28 days

�� Regimens: twoRegimens: two--three drug regimens three drug regimens

�� Close followClose follow--upup

Landovitz et al. NEJM 2009; 361: 1768-75; CDC4444

What was done?What was done?

�� Immunizations up to date: Td givenImmunizations up to date: Td given

�� No PEP administered No PEP administered

�� No Hep B vaccine or HBIGNo Hep B vaccine or HBIG

�� Testing for HCV and HIV baseline; Testing for HCV and HIV baseline;

followfollow--up ensured up ensured

4545

Case #3: The Case #3: The ““roofieroofie””incidentincident�� 1717--yearyear--old previously healthy male presents to the Emergency old previously healthy male presents to the Emergency

department. department.

�� He reports that he was at a party last evening and thinks that hHe reports that he was at a party last evening and thinks that he e was slipped a was slipped a ““roofieroofie””

�� He does not remember anything, but when he regained He does not remember anything, but when he regained consciousness, he realized that he had been subjected to nonconsciousness, he realized that he had been subjected to non--consensual anal intercourse. consensual anal intercourse.

�� He does not know whether or not a condom was used.He does not know whether or not a condom was used.

�� PMH: unremarkablePMH: unremarkable

�� Social history: no illicit substances, sexually active, engagesSocial history: no illicit substances, sexually active, engages in in protected intercourse (always)protected intercourse (always)

�� Meds: noneMeds: none

�� Physical exam: T 98.3Physical exam: T 98.3°°F; distraught exam otherwise within normal F; distraught exam otherwise within normal limitslimits

OTHER QUESTIONS? WHAT DO YOU DO AND RECOMMEND?OTHER QUESTIONS? WHAT DO YOU DO AND RECOMMEND? 4646

(Case 3): The roofie incident(Case 3): The roofie incident

A)A) Initiate prophylactic therapy with AZTInitiate prophylactic therapy with AZT

B)B) Patient does not meet criteria for PEP Patient does not meet criteria for PEP

treatment treatment

C)C) watch and waitwatch and wait

D)D) There are no available drugs to treat There are no available drugs to treat



E)E) Start HAART with 2 or 3 drug ARV Start HAART with 2 or 3 drug ARV

regimens for 28 daysregimens for 28 days4747

Sexual assault: First stepsSexual assault: First steps

�� Assault proceduresAssault procedures

�� Immunization status (Hep B, Hep A)Immunization status (Hep B, Hep A)

�� Vaccination (active and passive) if necessaryVaccination (active and passive) if necessary

�� Testing (Hep A, B, C, HIV)Testing (Hep A, B, C, HIV)

�� Antiretrovirals if exposure and risk deemed high*Antiretrovirals if exposure and risk deemed high*

–– Adherence counselingAdherence counseling

�� Close followClose follow--up and serial testingup and serial testing


PostPost--exposure prophylaxis (PEP) Guidelines:exposure prophylaxis (PEP) Guidelines:

NonNon--occupational exposureoccupational exposure

�� PerPer--contact risk of HIV transmission from sexual exposure varies contact risk of HIV transmission from sexual exposure varies

according to the nature of the exposure. Risks of sexual transmiaccording to the nature of the exposure. Risks of sexual transmission ssion

perper--contact transmission derived from observational studiescontact transmission derived from observational studies

�� 1 to 30% (receptive UAI); 1 to 30% (receptive UAI);

�� 0.1 to 10.0% ( insertive UAI and receptive vaginal intercourse)0.1 to 10.0% ( insertive UAI and receptive vaginal intercourse)

�� 0.1 to 1.0% with insertive vaginal intercourse0.1 to 1.0% with insertive vaginal intercourse

�� Oral sexOral sex

–– good risk estimates are lacking good risk estimates are lacking

–– Presumed lower risk of HIV transmissionPresumed lower risk of HIV transmission

–– case reports of HIV infections in persons with oral intercourse case reports of HIV infections in persons with oral intercourse as only as only

reported risk factorreported risk factor

–– Factors affecting acquisition: presence or absence of concomitaFactors affecting acquisition: presence or absence of concomitant nt

genital ulcer disease, trauma, cervical or anal dysplasia; circugenital ulcer disease, trauma, cervical or anal dysplasia; circumcision mcision

status; viral load in the genital compartment; virulence.status; viral load in the genital compartment; virulence.


4949

NonNon--occupational PEP: When should it be given?occupational PEP: When should it be given?

�� Consensus guidelines recommends for PEP for:Consensus guidelines recommends for PEP for:

–– exposed to known HIV+ source patient (source often unavailable)exposed to known HIV+ source patient (source often unavailable)

–– selected highselected high--risk populations with unknown HIV status among risk populations with unknown HIV status among

whom the seroprevalence of HIV infection is considered to be whom the seroprevalence of HIV infection is considered to be

sufficient to justify the toxicity and cost of treatment:sufficient to justify the toxicity and cost of treatment:

�� MSM; MSM&WMSM; MSM&W

�� commercial sex workerscommercial sex workers

�� injectioninjection--drug usersdrug users

�� persons with a history of incarcerationpersons with a history of incarceration

�� persons from a country/locale where the seroprevalence of HIV ispersons from a country/locale where the seroprevalence of HIV is ≥≥1% 1%

�� persons who have a sexual partner belonging to one of these groupersons who have a sexual partner belonging to one of these groupsps

�� Perpetrators of sexual assault are also considered to be at highPerpetrators of sexual assault are also considered to be at high risk for being risk for being

HIV+; this risk is sufficient for the consideration of PEP in thHIV+; this risk is sufficient for the consideration of PEP in the victime victim

PostPost--exposure prophylaxis (PEP) Guidelines exposure prophylaxis (PEP) Guidelines

for Nonfor Non--occupational exposure: occupational exposure:

What to give and for how long?What to give and for how long?

�� Extrapolated from occupational exposure Extrapolated from occupational exposure

and PMTCTand PMTCT

�� No efficacy data are available for this No efficacy data are available for this

strategy, but substantial safety and feasibility strategy, but substantial safety and feasibility

data have led to widespread acceptance.data have led to widespread acceptance.

�� Initiate as soon as possible, <36 hours ideal, Initiate as soon as possible, <36 hours ideal,

continue x 28 dayscontinue x 28 days


5252

Regimen Dose Advantage Disadvantage

2-drug

TDF/FTC 300/200mg once daily

well tolerated Nephrotoxicity

AZT/3TC 300/150mg twice daily

Preferred in pregnancy

Nausea, marrow toxicity, pill burden

3-drug

LPV/r + TDF/FTC or AZT/3TC

Once or twice daily High genetic barrier to resistance

GI toxicity, LFT abnormalities

ATV/r + TDF/FTC or AZT/3TC

Once or twice daily Well tolerated, once daily

Ritonavir to be refrigerated. Asymptomatic jaundice, increased LFTs

LPV/r + TDF/FTC or AZT/3TC

Once or twice daily High genetic barrier to resistance

28-day PEP regimens

Note: Nonadherence (70-80%)


(Case 3): The roofie incident(Case 3): The roofie incident

A)A) Initiate prophylactic therapy with AZTInitiate prophylactic therapy with AZT

B)B) Patient does not meet criteria for PEP Patient does not meet criteria for PEP

treatment treatment

C)C) watch and waitwatch and wait

D)D) There are no available drugs to treat There are no available drugs to treat



E)E) Start HAART with 2 or 3 drug ARV Start HAART with 2 or 3 drug ARV

regimens for 28 daysregimens for 28 days 5353

What was done?What was done?

�� The patient received no PEPThe patient received no PEP

5454

Case #3: Four weeks laterCase #3: Four weeks later……

�� The patient presents with fever to 40 F, malaise, sore The patient presents with fever to 40 F, malaise, sore throat, diffuse erythroderma throat, diffuse erythroderma

�� PE: generalized lymphadenopathy, diffuse body rashPE: generalized lymphadenopathy, diffuse body rash

WHAT OTHER QUESTIONS DO YOU HAVE?WHAT OTHER QUESTIONS DO YOU HAVE?

WHAT IS YOUR DIFFERENTIAL DIAGNOSIS?WHAT IS YOUR DIFFERENTIAL DIAGNOSIS?

5555

Differential DiagnosisDifferential Diagnosis

�� EpsteinEpstein--Barr virus mononucleosis Barr virus mononucleosis

�� Primary cytomegalovirus infectionPrimary cytomegalovirus infection

�� Influenza Influenza

�� Severe (streptococcal) pharyngitis Severe (streptococcal) pharyngitis

�� Drug reactionDrug reaction

�� Viral hepatitisViral hepatitis

�� Primary herpes simplex virus infectionPrimary herpes simplex virus infection

�� Secondary syphilisSecondary syphilis

�� ToxoplasmosisToxoplasmosis

�� RubellaRubella

�� BrucellosisBrucellosis

�� MalariaMalaria

�� Acute retroviral syndrome (ARS)Acute retroviral syndrome (ARS)5656

Acute Retroviral Syndrome (ARS)Acute Retroviral Syndrome (ARS)

�� Occurs in Occurs in ½½ to 2/3 of recently infected to 2/3 of recently infected individualsindividuals

�� Occurs 1 to 6 wks after exposureOccurs 1 to 6 wks after exposure–– peak 3 wks; lasts approx 14 dayspeak 3 wks; lasts approx 14 days

�� Underreported and underUnderreported and under--diagnoseddiagnosed

�� Nonspecific and variable presentationNonspecific and variable presentation

�� Symptoms last approximately 14 daysSymptoms last approximately 14 days

�� Labs: Labs: –– reduced total lymphocyte count, reduced total lymphocyte count, ↑↑ ESR, negative ESR, negative

monospot, monospot, ↑↑ LFTsLFTs

–– HIV Antibody test is likely negative;may not be HIV Antibody test is likely negative;may not be reliably positivereliably positive

�� Best test: HIV RNABest test: HIV RNA

�� PERIOD OF HIGH INFECTIVITY!!!PERIOD OF HIGH INFECTIVITY!!! 5757

Case #3: Four weeks laterCase #3: Four weeks later……

�� Evaluation : Evaluation :

–– Rapid strep Rapid strep –– negative; throat culture pendingnegative; throat culture pending

–– CBC w/differential: wbc 3.1CBC w/differential: wbc 3.1××101033//µµL; platelet L; platelet count, 85count, 85××101033//µµL)L)

–– LFTs elevatedLFTs elevated

–– EBV serologies EBV serologies –– consistent with past infectionconsistent with past infection

THOUGHTS?THOUGHTS?

5858

Case#3: HIV test ResultsCase#3: HIV test Results

�� HIV antibody negative; VL 500,000 HIV antibody negative; VL 500,000

copies/mL!copies/mL!

59593 months later HIV antibody positive

Natural History of HIV: Virologic and Natural History of HIV: Virologic and

Immunologic FeaturesImmunologic Features

6060

Why is it important to recognize ARS?Why is it important to recognize ARS?

�� Markedly elevated viremiaMarkedly elevated viremia

�� Transmissibility very high!!!!! Transmissibility very high!!!!!

�� Secondary preventionSecondary prevention

�� Opportunity to diagnose and get into careOpportunity to diagnose and get into care

�� +/+/-- treatment (highly debatable)treatment (highly debatable)

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Table 1: Theoretical Rationale for and Disadvantages of Initiating ARV Therapy During Acute Infection

Rationale for ARV therapy

•↓ risk of viral transmission

•Preserve HIV-specific immune function, including promoting the survival of CD4 cells that are involved in the initial response to HIV infection •Suppress the initial burst of viral replication and ↓ the magnitude of viral dissemination •Potentially ↓ the initial viral setpoint, which may ultimately affect the rate of disease progression •To potentially ↓ the emergence of viral mutations as a result of the suppression of viral replication

Disadvantages of ARV therapy

•Adverse effects on quality of life as a result of drug toxicities and complex treatment regimens •Potential for the development of drug resistance if therapy fails due to nonadherence or to insufficient suppression of viral replication, which may limit future treatment options •Earlier commitment to lifetime ARV therapy •Less time to educate the patient about ARV therapy •Insufficient data regarding effectiveness of early treatment

6262Adapted from Diagnosis and Management of Acute HIV Infection, HIV Clinical Guidelines from the NY State Dept of Health AIDS Institute, January 2010

Early treatmentEarly treatment

6363

http://www.topnews.in/files/HIV-Infants.jpg

Case 4: 9 year old early treated childCase 4: 9 year old early treated child

�� 9 year old adopted male 9 year old adopted male

�� Diagnosed with HIV at 2 months of ageDiagnosed with HIV at 2 months of age

–– HIV DNA PCR +HIV DNA PCR +

–– HIV RNA PCR of >750,000 copies/mLHIV RNA PCR of >750,000 copies/mL

–– Initial CD4 1029 (31.2%)Initial CD4 1029 (31.2%)

�� HAART (R/AZT/3TC) initiated at 2 months of ageHAART (R/AZT/3TC) initiated at 2 months of age

�� VL suppressed by 6 months of age and remained <50VL suppressed by 6 months of age and remained <50--

400 copies/mL400 copies/mL

�� No clinical symptomsNo clinical symptoms

MOTHER QUESTIONS: IS HE REALLY INFECTED?MOTHER QUESTIONS: IS HE REALLY INFECTED?6464


�� Is he really infected?Is he really infected?

�� What testing can be done to verify this?What testing can be done to verify this?

6565


�� HIV ANTIBODY TEST: HIV ANTIBODY TEST:

–– Negative (9 y/o)Negative (9 y/o)

–– HIV DNA PCR: varying results (+ and HIV DNA PCR: varying results (+ and --))

IS HE REALLY INFECTED?IS HE REALLY INFECTED?

WHAT OTHER TESTING CAN BE DONE TO VERIFY ?WHAT OTHER TESTING CAN BE DONE TO VERIFY ?

HIV culture (research basis)HIV culture (research basis)

6666

Dilemmas of early treatmentDilemmas of early treatment

�� No development of HIV specific ab response No development of HIV specific ab response

–– (2(2--7% adults; 267% adults; 26--75% infants) 75% infants)

–– Impact of ARV discontinuationImpact of ARV discontinuation

�� Reliability on ARVs to suppress virusReliability on ARVs to suppress virus

�� Lifelong therapy?Lifelong therapy?

�� Proof of infection Proof of infection

6767Kassulto S, et al. CID 2005 Mar 15;40(6):868-73; Kfutwah K, et al. JAIDS.2011 Oct 1;58(2):e43-6Luzuriaga K, et al. J Virol. 2000;74:6984-6991

Case 5: Restarting HAARTCase 5: Restarting HAART

6868

Out of options??

Case 5: Restarting HAARTCase 5: Restarting HAART

�� 16 y/o male with perinatally16 y/o male with perinatally--acquired HIVacquired HIV

�� PMH: PMH:

–– Chronic nonadherenceChronic nonadherence

–– AsthmaAsthma

–– developmental delaydevelopmental delay

–– uncircumciseduncircumcised

–– recent h/o gonorrhea/chlamydia recent h/o gonorrhea/chlamydia

–– Hep B nonHep B non--responderresponder

��

Lab data: Case 5Lab data: Case 5

�� CD4 268 (26%) (nadir= 154 (7/07)CD4 268 (26%) (nadir= 154 (7/07)

�� VL: 10K copies/mL (only once <400 VL: 10K copies/mL (only once <400

throughout treatment history)throughout treatment history)

7070

Case 5: ARVs and GenotypesCase 5: ARVs and Genotypes

�� Past ARV: Past ARV:

–– AZT monotherapyAZT monotherapy

–– AZT/3TC (10/2000AZT/3TC (10/2000--10/2002)10/2002)

–– LPV/r/DDI/TDF(11/02LPV/r/DDI/TDF(11/02--12/04)12/04)

–– EFV/ABC/3TC (12/04EFV/ABC/3TC (12/04--1/06)1/06)

–– LPV/r/TDF/FTC (1/06LPV/r/TDF/FTC (1/06-- unclear stop date) ?adherence; now off unclear stop date) ?adherence; now off

treatment for several monthstreatment for several months

�� Past Genotypes:Past Genotypes:

–– RT: 219Q, 67N, 69N, 70R, M184VRT: 219Q, 67N, 69N, 70R, M184V

–– PI: A71T, L63P, L90MPI: A71T, L63P, L90M

�� Most recent genotype: no mutations presentMost recent genotype: no mutations present

Case 5: What would you do?Case 5: What would you do?

A) You are excited that he has no mutations A) You are excited that he has no mutations

and start him on first line agents.and start him on first line agents.

B) Are concerned about hidden resistance B) Are concerned about hidden resistance

and therefore consider options with the and therefore consider options with the

past mutations and regimens in mind.past mutations and regimens in mind.

C) Restart his most recent regimen.C) Restart his most recent regimen.

D) No treatmentD) No treatment

Interpreting resistance: The latent reservoirInterpreting resistance: The latent reservoir

�� The virus persists in a latent form The virus persists in a latent form

in resting memory CD4 cells.in resting memory CD4 cells.

–– infected memory cells can survive for infected memory cells can survive for

many years. many years.

�� Following reFollowing re--exposure to the exposure to the

relevant antigen or other activating relevant antigen or other activating

stimuli (ARV), these cells can begin stimuli (ARV), these cells can begin

to produce virus again.to produce virus again.

�� The reservoir is a permanent The reservoir is a permanent

archive for wildarchive for wild--type virus and for type virus and for

drugdrug--resistant variants that arise resistant variants that arise

during treatment. during treatment.

�� Interruption in treatment results in Interruption in treatment results in

the reemergence of the original the reemergence of the original

wildwild--type virus; genotype type virus; genotype

misleadingmisleading Persaud D et al. J Virol. 2003

Case 5: Additional testing tools?Case 5: Additional testing tools?

�� TrofileTrofile®® assayassay

�� Genotype (not helpful at this time)Genotype (not helpful at this time)

�� Phenotype (not helpful at this time)Phenotype (not helpful at this time)

7474

Case 5: Designing a regimenCase 5: Designing a regimen

�� Past Genotypes:Past Genotypes:

–– RT: 219Q, 67N, 69N, 70R, M184VRT: 219Q, 67N, 69N, 70R, M184V

–– PI: A71T, L63P, L90MPI: A71T, L63P, L90M

Resistance interpretationResistance interpretation

--Minimal activity of NRTIsMinimal activity of NRTIs

--TDF with FTC most active of NRTIs TDF with FTC most active of NRTIs

--Some decreased activity of LPV/rSome decreased activity of LPV/r

--DRV and ATV may be more active than LPV/rDRV and ATV may be more active than LPV/r

7575

What specific ARVs What specific ARVs would you start?would you start?

What other aspects What other aspects should be considered?should be considered?

7676

Designing a new ARV regimenDesigning a new ARV regimen

�� Goal: Goal:

–– ≥≥2 fully active agents2 fully active agents

–– Consider context of patientConsider context of patient’’s life (i.e., pill s life (i.e., pill

burden, palatability)burden, palatability)------once daily, less pillsonce daily, less pills

–– Virologic suppressionVirologic suppression

–– Promotion of adherencePromotion of adherence——texting, close texting, close

followfollow--upup

Case 5: RecommendedCase 5: Recommended

�� DRV/r + TDF/FTC + ralDRV/r + TDF/FTC + ral

�� DRV/r + ETV + ral DRV/r + ETV + ral

�� ATV/r + TDF/FTC + ralATV/r + TDF/FTC + ral

�� Trofile test result: DM virus (no CCR5 Trofile test result: DM virus (no CCR5

antagonist activity)antagonist activity)

7878

7979

ComentComentáários o perguntas???rios o perguntas???

8080

OBRIGADO!!OBRIGADO!!

ReferencesReferences

�� Kirshenbaum SB, et al. Perspectives on Sexual & Kirshenbaum SB, et al. Perspectives on Sexual & Reproductive Health, 2004; 36(3)Reproductive Health, 2004; 36(3)

�� Landovitz et al. NEJM 2009; 361: 1768Landovitz et al. NEJM 2009; 361: 1768--7575

�� Puga A, Emmanuel P. Challenges in Puga A, Emmanuel P. Challenges in Pediatric/Adolescent HIV Case Studies. 15Pediatric/Adolescent HIV Case Studies. 15thth Annual HIV Annual HIV Conference of Florida/Caribbean AETC. 2006Conference of Florida/Caribbean AETC. 2006

�� http://www.fda.gov/oashi/aids/pedlbl.htmlhttp://www.fda.gov/oashi/aids/pedlbl.html

�� www.cdc.govwww.cdc.gov

�� http://www.aidsinfo.org/Guidelineshttp://www.aidsinfo.org/Guidelines

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