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Sally Hodder, MD New Jersey Medical School University of Dentistry and Medicine Newark, NJ

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

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Sally Hodder, MD New Jersey Medical School University of Dentistry and Medicine Newark, NJ

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  1. Sally Hodder, MD New Jersey Medical School University of Dentistry and Medicine Newark, NJ Treating HIV in Special Populations

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

  3. Antiretroviral Selection When Considering Pregnancy • 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 • DHHS guidelines.http://AIDSinfo.nih.gov/PerinatalGL

  4. Estimated Number of Perinatally Acquired AIDS Cases by Year of Diagnosis in the United States and Dependent Areas (1985-2006) No. of Cases Year of Diagnosis Note: Data have been adjusted for reporting delays and cases without risk factor information were proportionally redistributed.

  5. Antiretroviral Agents in Pregnancy *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

  6. Birth Defect Rate in LPV/r- Exposed Infants Similar to LPV/r-Unexposed 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 Birth Defect Prevalence for LPV/r-Exposed and -Unexposed Infants Roberts S, et al. XVII IAS; 2008; Mexico City. Abstract TUPE0120.

  7. LPV/r Pharmacokinetics in Pregnancy *P<.05 Third trimester vs postpartum †P<.05 Third trimester vs second trimester Best BM, et al. 15th CROI ;2008; Boston. Abstract 629.

  8. 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

  9. Primary and Secondary Syphilis: US Rates 1987–2006 Rate (per 100,000 Population) Male Female Total 2010 target Year http://www.cdc.gov/std/stats/SyphilisSlides2006.ppt

  10. 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% 31.1% Patients (%) 14.5% 11.0% AIDS Liver-Related Diseases CVD Cause of Death (n=1246) Weber R, et al. Arch Intern Med. 2006;166:1632-1641.

  11. Independent Predictors of Liver-Related Death Latest CD4 cell count (cells/mm3) <50 50-99 100-199 200-349 350-499 >500 16.06 11.54 7.14 3.95 1.67 2.01 HIV acquisition via IDU Hepatitis C status Negative Positive 6.66 Hepatitis B status Negative Positive 3.73 IDU, injection drug use. Multivariate analysis. Not shown: Age per 5 years (1.32). 0.2 1.0 10 100 Relative Risk of Death Weber R et al. Arch Intern Med. 2006;166:1632-1641.

  12. 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.

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

  14. GESIDA Cohort: SVR Reduces Risk for Liver-Related Morbidity & Mortality No SVR SVR N = 711 HIV/HCV patients 6.9 Death 0.9* 3.7 Liver-related death 0.5* 9.1 Liver decompensation 0.5* 1.8 Hepatocellular carcinoma 0 2.2 Liver transplantation 0* 0 10% 20% Frequency of Events During Follow-up (%) *P < .05 Berenguer J, et al. 15th CROI; 2008; Boston. Abstract 60.

  15. NRTI Choice and HCV Treatment Response in Coinfected Patients Study #11 Study #22 Study #33 60% 50% 40% 30% 20% 10% 0% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% P =0.26 P =0.02 P =0.001 % SVR n= 238 n= 481 n= 70 n= 186 n= 56 n= 118 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.

  16. 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

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