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