sally hodder, md new jersey medical school university of dentistry and medicine newark, nj

Sally Hodder, MDNew Jersey Medical School

University of Dentistry and MedicineNewark, NJ

Treating HIV in Special PopulationsTreating HIV in Special Populations

Reproductive Issues in HIV-Infected Women

• Important to assure that reproductive intentions/needs are discussed Nearly half of HIV-infected women were not asked by HIV provider

about this issue1

• Contraception Drug interactions between oral contraceptives (OCs) and antiretroviral

agents documented

• Amprenavir (and probably fosamprenavir) increase ethinyl estradiol (EE) and norethindrone (NE) levels while OCs decrease amprenavir levels2

• Lopinavir/ritonavir decreases EE 42%2

• Atazanavir increases EE 48% and NE 110%2

1. Bridge DA. XVII IAS; 2008; Mexico City. Abstract TUPE0911. 2. DHHS guidelines.hrrp://AIDSinfo.nih.gov

• Antiretroviral selection in women considering pregnancy Treatment guidelines should be followed Evaluate and control therapy–associated side effects

(e.g., hyperglycemia, anemia) EFV – FDA Class D; associated with neural tube

defects in animals1

1. DHHS guidelines.http://AIDSinfo.nih.gov/PerinatalGL1. DHHS guidelines.http://AIDSinfo.nih.gov/PerinatalGL

Antiretroviral Selection When Considering Pregnancy

Estimated Number of Perinatally Acquired AIDS Cases by Year of Diagnosis in the United States and

Dependent Areas (1985-2006)

Note: Data have been adjusted for reporting delays and cases without risk factor information were proportionally redistributed.

Year of Diagnosis

No

. of

Cas

es

Antiretroviral Agents in Pregnancy

NRTI NNRTI PI

Recommended* ZDV

3TC

Nevirapine (NVP)** Lopinavir (LPV/r)

Alternative Didanosine (ddI)

FTC

Stavudine (d4T)

Abacavir (ABC)

Indinavir/r (IDV/r)

Nelfinavir (NFV)

Saquinavir (HGC)/r

Insufficient

data

TDF* Atazanavir (ATV)

Darunavir (DRV)

Fosamprenavir (FPV)

Tipranavir (TPV)

Not recommended Zalcitabine (ddC) EFV

*TDF/FTC recommended for women with chronic hepatitis B** For use with CD4 count less than 250 cells/mm3

r=boosted with ritonavir.Public Health Service Task Force.Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health&Interventions to Reduce Perinatal HIV Transmission in the United States. July 8, 2008

Birth Defect Rate in LPV/r- Exposed Infants Similar to LPV/r-Unexposed

% Prevalence (95% CI)

LPV/r-First trimester 1.9 (0.6 – 4.3)

LPV/r-Second/third trimester 2.6 (1.6 – 4.1)

LPV/r- Any trimester 2.4 (1.5 – 3.6)

MACDP 2.67

• 987 LPV/r exposures with pregnancy outcomes 955 Live births

• Birth defect prevalence compared with that of the Metropolitan Atlanta Congenital Defects Program (MACDP) population-based surveillance system

Roberts S, et al. XVII IAS; 2008; Mexico City. Abstract TUPE0120.

Birth Defect Prevalence for LPV/r-Exposed and -Unexposed Infants

LPV/r Pharmacokinetics in Pregnancy

Second Trimestern=7

Third Trimestern=25

Postpartumn=19

LPV/r Dose 400/100 bid 600/150 bid 400/100 bid

AUC0-12 72 97* 129

Cpre-dose (µg/mL) 5.3 6.7† 8.4

Cmax (µg/mL) 9.1 10.7* 14.6

*P<.05 Third trimester vs postpartum†P<.05 Third trimester vs second trimester

Best BM, et al. 15th CROI ;2008; Boston. Abstract 629.

Conclusions

• HIV care providers must address contraception and preconception care

• Antiretroviral therapy should be instituted or continued during first trimester if indicated for HIV care of the pregnant woman

• Emerging data now available with LPV/r suggest similar rates of birth defects in ART-exposed and -unexposed infants

• Pharmacokinetics of some antiretroviral agents are altered in pregnancy Dose adjustments may be necessary

• Infants of mothers with chronic hepatitis B should receive hepatitis B immune globulin; initiate hepatitis B vaccination within the first 12 hours after birth

Primary and Secondary Syphilis: US Rates 1987–2006

http://www.cdc.gov/std/stats/SyphilisSlides2006.ppt

Rate (per 100,000 Population)

MaleFemaleTotal2010 target

Year

Liver Disease Is a Leading Cause of Death in HIV-Infected Patients (1999-2004)

• D:A:D study (n=23,441) Median follow-up: 3.5 years

• Baseline characteristics Nadir CD4: 200 cells/mm3

Previous AIDS: 26.5% HCV positive: 22.5% Active HBV infection: 6.8% Receiving combination

antiretroviral therapy: 88.7%

• Liver deaths (n = 181) CD4 at death = 196 cells/mm3 HIV < 400 copies/mL at death

= 54.6%

Weber R, et al. Arch Intern Med. 2006;166:1632-1641.

Cause of Death (n=1246)

AIDS Liver-RelatedDiseases

CVD

Patie

nts

(%)

31.1%

14.5%

11.0%

Independent Predictors of Liver-Related Death

Latest CD4 cell count (cells/mm3)<50

50-99

100-199

200-349

350-499

>500

HIV acquisition via IDU

Hepatitis C statusNegative

Positive

Hepatitis B statusNegative

Positive

Weber R et al. Arch Intern Med. 2006;166:1632-1641.

0.2 1.0 10 100

Relative Risk of Death

16.06

11.54

7.14

3.95

1.67

2.01

6.66

3.73

IDU, injection drug use.Multivariate analysis.Not shown: Age per 5 years (1.32).

Impact of HCV on HIV Infection

• HCV impact on HIV Meta-analysis of 8 trials (N=6216 patients)

• HIV/HCV-coinfected patients gain 33.4/mm3 fewer CD4 cells than HIV-monoinfected patients

• No clinical significance EuroSIDA and Johns Hopkins HIV cohorts

• After adjusting for confounding factors (eg, IDU), HIV/HCV-coinfected patients do not have a greater risk of progressing to AIDS

• Increased risk of ART-induced liver injury Grade 3/4 ALT and AST elevations ~ 3-fold higher in coinfected

persons than in monoinfected

Miller MF, et al. Clin Infect Dis. 2005;41:713-720.Rockstroh JK, et al. J Infect Dis. 2005;192:992-1002.

HIV and ART: Impact on SVR

• CD4 > 350 cells/mm3 – trend toward higher SVR rate for genotype 1

• PIs and NNRTIs APRICOT: PI or NNRTI

associated with increased SVR (p = .034)

• NRTIs Didanosine → mitochondrial

toxicity Zidovudine → anemia Abacavir → decreased viral

response?

SVR by CD4 (Gt 1)

13

19

32

0

10

20

30

40

< 200 200 to<350

> 350

Opravil M et al. JAIDS 2007;47:36-49

GESIDA Cohort: SVR Reduces Risk for Liver-Related Morbidity & Mortality

Berenguer J, et al. 15th CROI; 2008; Boston. Abstract 60.

*P < .05

1.8

20%

0.5*

0.5*

0.9*

Frequency of Events During Follow-up (%)

No SVR SVR

0 10%

Death

Liver-related death

Liver decompensation

Hepatocellular carcinoma

Liver transplantation

6.9

3.7

9.1

02.2

0*

N = 711 HIV/HCV patients

NRTI Choice and HCV Treatment Response in Coinfected Patients

1. Mira J et al. 15th CROI; 2008; Boston. Abstract 1074.2. Gonzalez-Garcia JJ et al. 15th CROI; 2008 Boston. Abstract 1076.3. Mereno A et al. 15th CROI; 2008; Boston. Abstract 1075.

% S

VR

n= 70 n= 186

P =0.02

n= 238 n= 481 n= 56 n= 118

P =0.001

P =0.26

Study #11 Study #22 Study #33

45%

40%

35%

30%

25%

20%

15%

10%

5%

0%

60%

50%

40%

30%

20%

10%

0%

Conclusions

• Syphilis is increasing in incidence. It should always be considered in appropriate clinical presentations

• Liver disease is a leading cause of death in HIV-infected persons

• Lower CD4 cell count and presence of hepatitis C or hepatitis B coinfection increases risk of liver-related death

• Effective treatment of hepatitis C decreases liver-related morbidity and mortality in HIV/hepatitis C coinfected persons

• Antiretroviral choices may affect response rates to hepatitis C treatment