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Sally Hodder, MD New Jersey Medical School University of Dentistry and Medicine Newark, NJ. Treating HIV in Special Populations. Reproductive Issues in HIV-Infected Women. Important to assure that reproductive intentions/needs are discussed - PowerPoint PPT Presentation
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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