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Carmen D. Zorrilla, MD Professor OB-GYN UPR School of Medicine PI Maternal Infant Studies Center

A Multicultural Caribbean United Against HIV/AIDS Mother to Infant HIV Transmission: State of the Art. Carmen D. Zorrilla, MD Professor OB-GYN UPR School of Medicine PI Maternal Infant Studies Center. We make a living by what we get. We make a life by what we give. ~Winston Churchill~.

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Carmen D. Zorrilla, MD Professor OB-GYN UPR School of Medicine PI Maternal Infant Studies Center

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  1. A Multicultural Caribbean United Against HIV/AIDSMother to Infant HIV Transmission: State of the Art Carmen D. Zorrilla, MD Professor OB-GYN UPR School of Medicine PI Maternal Infant Studies Center

  2. We make a living by what we get. We make a life by what we give.~Winston Churchill~

  3. Possible Routes of Transmission In-utero At Birth During Breastfeeding

  4. Incidence of Perinatally-Acquired AIDS United States, 1985-2000 81% PACTG 076 decline 500 USPHS ZDV recs 400 300 No. of Cases 200 100 0 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 Half Year of Diagnosis (Reported through December 2000)

  5. Perinatal HIV TransmissionPuerto Rico (1990 – 2002) Sources: Ryan White Title IV Program, OCASET, 2002; Gamma Project; CEMI

  6. Antiretroviral Therapy During Pregnancy : Indications • Maternal: Management of HIV Infection • Fetal: Prevention of Perinatal HIV Transmission

  7. Initial Perinatal Trials Focused on Prevention of In Utero and Intrapartum Transmission AP IP PP(baby, mother or both) 14 wks 28 wks 36 wks 3d to 1 wk 6 wks 076 NonBF NonBF Thai (Harvard) NonBF Thai (Harvard) NonBF Thai (Harvard), BMS IvC (ANRS), PETRA, Thai (Harvard) BF/NonBF Thai (CDC), IvC (CDC) NonBF/BF PETRA, 012, SAINT BF PETRA BF PP: Minimal duration? Is it needed? AP: Minimum duration? Is it needed? IP: Work alone?

  8. Initial Perinatal HIV Clinical TrialsEfficacy of Regimens Breast-fed Formula-fed AZT AZT/ AZT AZT NVP AZT/ NVP AZT AZT/ AZT 3TC 3TC 3TC

  9. Effect of Breastfeeding on PMTCT Prophylaxis 37% No ARV, BF 22.5% AZT AP-IP 20% 18.1% AZT/3TC IP-PP 16.5% 15.7% NVP IP-PP 14.9% AZT/3TC AP-IP-PP 11.8% 8.9% 8.6% 076 AZT-no BF 5.7% 1.6% 316 comb-no BF Infant Age

  10. Mother To Child Transmission (MTCT): Treatment Options • ZDV long course (076) • ZDV short course (Thai 28 wks) • ZDV shorter course (36wks) • ZDV/3TC • NVP single dose (SD) • NVP plus infant ZDV • ZDV short course /NVP SD • HAART

  11. Group A: Single-dose NVP to both mother (200 mg) and infant (6 mg) + AZT n = 724 Group B: Single-dose NVP (200 mg to mother) + Placebo (to infant) + AZTn = 721 Group C: Placebo (to mother) + Placebo (to infant) + AZT n = 399 Single-dose NVP added to standard AZT regimen for prevention of MTCT in Thailand Lallemant M et al. 11th Retrovirus Conf, Feb 2004 Abs 40LB Delivery before interim analysis Final as-treated Women: ZDV prophylaxis in 3rd trimester Infants: 1 wk ZDV + formula feeding Mother-infant pairs n = 1844 P = .00026 6.3% 1.1% 2.8% 2.0% NS

  12. Addition of Single-Dose Maternal/Infant NVP toAZT is Most Effective at Higher Maternal RNA Levels and lower CD4 counts (not shown)Lallemant et al. 11th Retrovirus Conf, Feb 2004 (abs 40LB) HIV RNA Comparing Difference in Transmission Rates AZT/Placebo-Placebo and AZT/NVP-NVP

  13. Short-Course AZT + Single-Dose Maternal/Infant NVPThailand Studies (Formula-Fed Infants):Longer Maternal Therapy = Lower Transmission Lallemant M et al. 11th Retrovirus Conf, Feb 2004 Abs 40LB AZT Backbone* *If mom <4 wk AZT, infant gets 4 wks AZT 28 wk oral 1 wk NVP NVP Transmission 2.0% (95% CI 1.2-3.4%) [N=693] Chalermchokcharoenkit et al. 11th Retrovirus Conf, Feb 2004 (abs 96) AZT Backbone 34-36 wk oral 4 wk NVP NVP Transmission 4.6% (95% CI 2.5-8.5%) [N=220]

  14. One Week of AZT Added to Single-Dose Infant NVP Improves Efficacy When No Maternal IP NVP DoseTaha T et al. Lancet 2003;362:1171-7 -- NVAZ StudyTaha T. 2002 AIDS Conf, Barcelona Abs ThPpD2146 MotherInfant p=0.03 Stratified: Late Presenter vs Early Presenter (got maternal NVP) 20.9% 15.3% NB NVP NB NVP AZT 1 wk 15.4% 15.3% IP NVP NB NVP IP NVP NB NVP AZT 1 wk When maternal intrapartum NVP dose is received, addition of AZT doesn’t offer benefit

  15. PHPT-2: Single-Dose NVP + Short-Course AZTResponse to Treatment Sub-studyJourdain et al. 11th Retrovirus Conf, Feb 2004 (Abs 41LB) • After the PHPT-2 clinical trial, women were placed on NNRTI-based HAART (most d4T/3TC/NVP) for clinical and/or CD4 indications. There were 213 women with prior SD NVP exposure and 42 without. • There were no differences in immunologic or virologic responses to <400 RNA at 3 and 6 mo. • Women with prior NVP exposure had lower response to <50 at 6 months (only 27 women) • Women with NVP resistance mutations had lower response overall

  16. Summary: Virologic Response (<400 & <50) to NNRTI-Based Therapy by Prior History SD NVPJourdain et al. 11th Retrovirus Conf, Feb 2004 (Abs 41LB) <400 copies/mL <50 copies/mL • Baseline 3 Months 6 Months

  17. WHO Statement: ARV and MTCT in resource-limited settingsExpert consultation, Geneva, 5-6 February 2004 • Women who need ARV for their own health should receive it • Women who do not need treatment should be offered ARV prophylaxis to prevent MTCT • The most efficacious regimen is ZDV from 28 wks with single dose NVP at the onset of labor and single dose NVP plus one week ZDV for the infant

  18. WHO Statement: ARV and MTCT in resource-limited settingsExpert consultation, Geneva, 5-6 February 2004 • Alternative (but less efficacious) regimens include: • ZDV alone (28 wks) and 1 week for the infant, • ZDV/3TC from 36wks, and 1 week for mother and infant, and • Single NVP for mother and infant • The selection should be based at national level based on efficacy, safety, drug resistance, feasibility and acceptability

  19. Mode of Delivery and Perinatal HIV Transmission: Meta-Analysis from 15 Prospective Cohort StudiesThe International Perinatal HIV Grp. N Engl J Med 1999;340:977-87 8,533 Mother-Infant Pairs from 15 Studies

  20. Effect of C/S on MTCT Transmission(PACTG 367 Chart Abstraction Study) • Transmission rate compared for elective C-section vs all other modes of delivery (n=3,081) • HIV-1 RNA < or > 1000 copies/mL • 1 drug vs multidrug therapy • No difference between delivery modes in women with HIV-1 RNA < 1000 copies/mL receiving HAART Shapiro D, et al. #99

  21. Pregnancy in Perinatally HIV-Infected adolescents and Young Adults– PR 2002(n= 8 adolescents and 10 pregnancies) MMWR February 28, 2003/52(08); 149-151 * All infants were HIV-uninfected

  22. Number of perinatally HIV-infected adolescents and young adults reporting selected behavioral and social characteristics (PR 2002)

  23. Before making any important decision-declaring a war, moving with his companions to another plain, choosing a field in which to sow seed- the warrior asks himself: “How will this affect the fifth generation of my descendants?” A warrior knows that everything a person does has enduring consequences and he needs to understand what kind of world he is leaving behind for that fifth generation. Paulo Coelho

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