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Antiretrovirals in Pregnancy: Beyond Combivir Kaletrao
 

Antiretrovirals in Pregnancy: Beyond Combivir Kaletrao

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Michael Kavanaugh, MD, of U.S.Navy Medicine, presents "Antiretrovirals in Pregnancy: Beyond Combivir Kaletrao"

Michael Kavanaugh, MD, of U.S.Navy Medicine, presents "Antiretrovirals in Pregnancy: Beyond Combivir Kaletrao"

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    Antiretrovirals in Pregnancy: Beyond Combivir Kaletrao Antiretrovirals in Pregnancy: Beyond Combivir Kaletrao Presentation Transcript

    • The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
    • Michael Kavanaugh 4 October 2013
    •  I have no commercial interests or financial relationships associated with topics discussed.  I will be not be discussing off-label use of medications
    • 27 year old HIV+ female (diagnosed 2005 CD4 878/39%, undetectable) on FTC/TDF/RAL presents with planned pregnancy 7w2d following Intrauterine insemination (IUI)
    •  Diagnosed with HIV 2005 following sexual assault- initial CD4 299  Initially on EFV/FTC/TDF-undetectable for 7 years  Changed to FTC/TDF+Raltegravir in March 2013  Pt expressed desire for pregnancy-stopped Atripla  Counseled on options including Combivir/Kaletra  Had been on Depo-Provera until December 2012  Husband attempted pre-exposure prophylaxis (Truvada) but was unable to tolerate  Pursued IUI-successful on 1st attempt  Obtained preliminary prenatal US-normal
    •  HIV (as described)  ADHD (as child)-previously on methylphenidate  Not currently on medications  Bipolar (diagnosed age 10)  Not currently on medications  HPV+, no other STDs  SH Married since 2011, College student-expected graduation June 2014, no tobacco or alcohol  Meds: FTC/TDF, Raltegravir, prenatal vitamin  Allergies-None
    •  Some morning sickness & minor constipation  No fevers, chills, new lymphadenopathy or respiratory complaints
    •  T98.6 BP 112/79 P84 R16  Gen pleasant, healthy appearing, NAD  HEENT normocephalic, pupils reactive, throat wnl  CV RRR no murmur  Resp cta (b)  Abd +bs, soft, NT, ND (not noticeably gravid yet)  Ext no edema
    •  CD4 878/39, %Viral Load <20  HCG 777,100 from 361,100 two days prior  CBC 7.3/14/42.1/362  Lytes 141/3.8/103/25/11/0.8/101 Ca 9.7 Mg 2.3  Bili 0.1 TP 6.9  Alk P 113 ALT 27 AST 22 LDH 157
    •  Prevention of Mother to Child Transmission  Teratogenicity  Choice of Medication  Combivir + Kaletra  Truvada, Raltegravir (Choice when discussing options with our patient)  Preterm labor  Low Birth Weight  Infant Prophylaxis  Caesarian Section
    •  Since 1994 New England Journal article by Connor EM et al.  477 HIV+ mothers  Interventions arm-antepartum ZDV and infant AZT for 6 weeks  Transmission decreased 25.5% to 8.3%  While on ZDV infants had lower Hb but normalized  1st stage I Clinical Trial 1985  FDA Approved for use March 20, 1987  Anemia-most common side effect (reversible)
    •  Which of the following statements is TRUE about maternal to child transmission (MTCT) of HIV?  The majority of MTCT occurs at or just before delivery (50%) with an additional 25% occurring antenatally and 25% postnatally through breast-feeding  The risks of MTCT antiretroviral prophylaxis from in utero or neonatal exposure outweighs the benefits  The rate of HIV infection in infants who are breastfed is the same as in those who are not breastfed by HIV seropositive mothers  HIV has not been detected in human breast milk  Caesarian section should not be considered for HIV seropositive women in labor who are on ARVs with a viral load of >1000
    •  Which of the following statements is TRUE about maternal to child transmission (MTCT) of HIV?  The majority of MTCT occurs at or just before delivery (50%) with an additional 25% occurring antenatally and 25% postnatally through breast-feeding  The risks of MTCT antiretroviral prophylaxis from in utero or neonatal exposure outweighs the benefits  The rate of HIV infection in infants who are breastfed is the same as in those who are not breastfed by HIV seropositive mothers  HIV has not been detected in human breast milk  Caesarian section should not be considered for HIV seropositive women in labor who are on ARVs with a viral load of >1000
    •  Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States  Last updated July 31, 2012
    •  NNRTIs-Didanosine and stavudine removed from alternatives  PIs- Atazanavir/r is now preferred as is lopinavir/r (for treatment naïve)  Previously alternative  Integrase Inhibitor-Raltegravir-moved from insufficient data to use in special circumstances
    •  Treat mother & reduce transmission  Generally-HIV+ pregnant women in 1st trimester should continue regimen if tolerating and effective (AII)  Choice of ART (childbearing)-prior to pregnancy  Effective treatment  HBV status  Teratogenicity of drug (should pregnancy occur)  Serodiscordant couple “treatment of infected partner may not be fully protective against sexual transmission of HIV”  Recommend treating HIV infected partner (AI if CD4<550)  PrEP may be offered CIII
    •  Infant transmission study-enrolled 1542 HIV-1 women 1990-2000 in US (WITS)  Prospective cohort  Measured HIV RNA levels  Transmission Based on Regimen  No ART (396 women) 20%  ZDV alone (710 women) 10%  Dual therapy (186 women) 4%  3 drugs (250 women) 1.2%  Transmission Based on Viral Load  >30,000 copies/ml 23% (115 women)  <400 copies/ml 1% (32 women) –undetectable at that time
    • Trimesters Treated Number /Trimester ZDV only Dual ART HAART 3rd 319 15.8 6.2 3.6 2nd & 3rd 409 8.4 4.3 0 1st, 2nd & 3rd 418 8.8 0 0
    •  Treatment Naïve  Obtain genotype prior to initiation-don’t wait for results  When to start?  Based on CD4 count, viral load, maternal nausea  Immediate versus week 12?  All should receive at least antepartum ART (regardless of CD4)  Prevention of perinatal transmission  On ART at initial prenatal visit  Efavirenz-concern of neural tube defects in first 5-6 weeks of pregnancy  If on EFV at recognition of pregnancy (>4-6 wks), may be unnecessary to change (affect on viral load)  Recommendation-continue at that point  Pre-pregnancy counseling  ARV which does not include Efavirenz should be strongly considered in women who are planning pregnancy or not using appropriate contraception (BIII)
    •  Zidovudine/lamivudine + lopinavir/ritonavir  Zidovudine/lamivudine + atazanavir/ritonavir  Tenofovir/emtricabine/efavirenz  Tenofovir/lamivudine +atazanavir/ritonavir  Tenofovir/lamivudine +maraviroc
    •  Zidovudine/lamivudine + lopinavir/ritonavir  Zidovudine/lamivudine + atazanavir/ritonavir  Tenofovir/emtricabine/efavirenz  Tenofovir/lamivudine +atazanavir/ritonavir  Tenofovir/lamivudine +maraviroc
    • Drug Pk Concerns in pregnancy Lamivudine Recommend No change No evidence of human teratogenicity, benefit if HBV coinfected, combined w/ ZDV (Combivir) High placental transfer Zidovudine Recommend Not signif (No dose Δ) No evidence of human teratogenicity, well tolerated High placental transfer Abacavir Alternative Not signif (No dose Δ) No evidence of human teratogenicity, hypersensitivity reactions (5-8%) Emtricibine Alternative Lower in 3rd trimester (No dose Δ) No evidence of human teratogenicity, benefit for HBV coinfected High placental transfer Tenofovir Alternative/ Preferred (HBV) AUC lower in 3rd trimester No evidence of human teratogenicity, preferred for HBV coinfected (with 3TC or FTC), monitor renal function, Monkey studies- double doses –decreased fetal growth and reduction in fetal bone porosity within 2 months of therapy Clinical Studies-bone demineralization with chronic use High placental transfer
    • *Preferred NNRTI-just really not preferred Drug Pk Concerns in pregnancy Nevirapine* (No dose Δ) No evidence of human teratogenicity Not for CD4>250 (life-threatening hepatotoxicity) High placental transfer Efavirenz AUC decrease 3rd trimester (No dose Δ) Class D (anencephaly, anopthalmia, cleft palate) Monkeys with EFV 3/20 (15%) 4 case reports and 1 prospective study with neural tube defects (1st trimester exposure) Risk of NT defect only limited to 1st 5-6 weeks, Recommend-continue if pregnancy recognized at 6 weeks (CIII) Etravirine Limited data Only 23 1st trimester exposures reported No evidence of teratogenicity in rats Rilpivarine No Pk studies in humans No published human data. No evidence of teratogenicity in rats or rabbits.
    • *ATV-package insert recommends BID dose in 2nd and 3rd trimester for treatment experienced only Drug Pk Concerns in pregnancy Atazanavir/r Preferred Decreased concentration *Increase dose 2nd & 3rd trimester Experienced vs. all No evidence of human teratogenicity, question about bilirubin-not seen clinically Do not use with both TDF and H2 receptor antagonist See PI in pregnancy articles Lopinovir/r Preferred 2nd & 3rd trimester Increase dose No evidence of human teratogenicity Low placental transfer Darunavir Alternative Concentrations decreased 23-28% in 3rd trimester Recommed BID Insufficient data to assess teratogenicity No evidence in in mice, rats or rabits Saquinavir/r Alternative Twice daily recommended Insufficient data to assess teratogenicity Issues with QT prolongation
    •  Didanosine-increased rate of birth defects compared to general population (19/409) 4.3%with 1st trimester use, (20/460) 4.3% with 2nd and third trimester  Stavudine-No evidence of human teratogenicity, lactic acidosis (occasionally fatal) in pregnanty women  Do not use with ddI or ZDV  Indinavir-No evidence of teratogenicity  Concern with potential for renal stones  Nelfinavir-No evidence of teratogenicity  Raltegravir-Recently upgraded from insufficient data  Limited human experience  Increased skeletal variants in rats, NO DEFECTS rabbits  Variable levels in 3rd trimester-No dose adjustment recommended  High Placental transfer
    •  Insufficient data-No teratogenicity in rats, rabbits  Fosamprenavir  Tiprinavir  T20 (Enfuvirtide)  Maraviroc
    • Because clinically significant resistance to protease inhibitors (PIs) is less common than resistance to non-nucleoside reverse transcriptase inhibitors in ARV-naive individuals in general, a ritonavir-boosted PI-based regimen should be initiated (AIII).
    • Clinicians should be aware of a possible small increased risk of preterm birth in pregnant women receiving protease inhibitor (PI)-based combination antiretroviral regimens; however, given the clear benefits of such regimens for both a woman’s health and prevention of mother-to-child transmission, PIs should not be withheld for fear of altering pregnancy outcome (AII).
    •  Combination Antiretroviral Use and Preterm Birth. JID. Watts H. et al. 2013.  1869 births (born of HIV+ mothers)-Cohort  18.6% (346)preterm, 7.3%(135) Small for gestational age  Protease Inhibitors resulted in higher preterm birth OR 1.55 compared to NNRTI or triple NRTI regimens  If exposure was 3rd trimester only-no statistical significance  Women evaluated from 22 weeks pregnancy till 1 week post-partum  Multiple racial and socioeconomic factors associated with preterm birth, also low CD4 (<200 copies/mL)
    •  Protease inhibitor-based antiretroviral therapy and glucose tolerance in pregnancy: AIDS Clinical Trials Group A5084. Hitt J, et al. 2007 Am J Obstet Gyn.  149 HIV+ women (73 on PIs, 76 other)  Abnormal Glucose Tolerance PI 26/73 versus 33/76  Not statistically significant  Gestational DM (PI 8%, other 10%-not significant)  HIV+ overall, 38% 57/149-Impaired Glucose Tolerance  General population 20-25%  HIV+ Gestational DM 9%  General population 2-5%
    •  1st line for HIV+ non-pregnant and pregnant with HIV/HBV coinfection  Alternative for HIV+ pregnant  Antiretroviral Pregnancy Registry-no adverse events (1219 pregnancies-1st trimester exposure)
    •  US based cohort of 2029 children  TDF 444 mothers (21%)  Evaluated Small for Gestational Age (SGA), Low Birth Weight (LBW), Weight for age-z-score (WAZ), length for age z score (LAZ), head circumference for age (HCAZ)  No difference for SGA, LBW & newborn LAZ and HCAZ  One year LAZ and HCAZ were smaller  Authors uncertain of clinical significance
    •  Pregnant Rhesus macaques-received TDF (double dose)- Tarantal et al. J Acquir Immune Defic Syn 2002  TDF group (n=4)-dosed at different times (20-150 days)  Lower crown-rump length  Lower body weight  Smaller adrenals  No difference -head, arm or chest circumference or extremity bone length  vanRompay et al Antimicrob Agents Chemother 2004.  39 infant macaques-varying doses-no adverse effect on health or growth  Separate issue-High dose TDF administered to infant macaques did show growth retardation  Lower Dose TDF-effect not observed-VonRompay 2008  High dose had effect on DEXA, no effect on low dose  No effect on renal failure with TDF
    •  Multicenter Observational Study 68 enrolled  TDF 33, no-TDF exposure 35  No difference between groups for low birth weight or birth length  Bone health not affected
    •  High neonatal concentrations of raltegravir following transplacental transfer in HIV-1 positive pregnant women. Mckeown D et al. AIDS. 2010.  Favorable side effect profile, no effect on CYP450, rapid reduction in viral load, increase CD4  3 cases reported of late term use in pregnancy-goal rapid reduction of viral load with MDR virus  Patients from Uganda, Ghana, Zimbabwe  Evaluated raltegravir concentrations after delivery  All infants HIV negative at 12 weeks  To date, no adverse events with mother
    •  HIV/HCV coinfected Italian woman-38 weeks  At time of pregnancy Truvada/RAL  CD4 543 with VL<50 coplies/mL  Changed to ZDV, 3TC, LPV/r (per guidelines)  Unable to obtain viral suppression-changed to DRV/r bid at 8 weeks  Poor adherence to new regimen  Wk 25, VL 189 copies/mL  Wk 38 CD4 350 and VL 75,584 copies/mL  Previous meds FTC, TDF, d4T, NVP, LPV/r, ATV/r, RAL
    •  No nevirapine (K103R mutation) & CD4>250  Added TDF and RAL to current regimen  9 days after start of RAL, pt delivered  IV ZDV added at time of delivery  VL decreased to 260 copies/mL at time of delivery (2.4 log decrease in 9 days)  Pt received 6 weeks post-natal ZDV/3TC and at birth and 1 month HIV negative  Cord to maternal level (RAL) 1.06 compared to DRV levels 0.36
    •  Per AIDS-info  Addition of Raltegravir in 3rd trimester neither endorsed nor rejected, but discussed as option Currently being evaluated by study at UCSF & International Maternal Pediatrics Adolescent AIDS Trial (IMPAACT)
    •  IV zidovudine is no longer required for HIV infected women on ART if HIV RNA<400 copies/ml  If HIV RNA>400 copies/ml (or unknown)  IV Zidovudine  Infant ART  Neonatal zidovudine (birth through 6 weeks)  Dosing depends on weeks of gestation  Start within 6-12 hours of birth  UK-recommended for only 4 weeks (if mother on ART)  If no antepartum ART  Higher dose ZDV + nevirapine (3 doses in 1st week)  Test infants at 14-21 days, 1-2 months, and 4-6 months  HIV cDNA PCR
    •  UK 4 weeks since 2005  Prospective cohort Spain  171 patients  133 received 6 weeks  33 received 4 weeks  All bottle fed (exclusively)  No statistical difference in transmission  No statistical difference in Hb at 6 weeks or 3 months (12.1 vs 13.1), MCV lower in 4 week group-earlier recovery  US-Six weeks since PACTG-076  Other Post-Exposure prophylaxis is only 4 weeks
    •  HIV RNA monitor at initial visit  Repeat 2-4 weeks after starting ART  Repeat monthly until undetectable  Every 3 months until delivery (**34-36 weeks**)  Viral Suppression should be obtained 16-24 weeks  CD4-every 3 months during pregnancy (BIII)  Every 6 months on ART for >2-3 years (maybe less?)  Genotype-treatment naïve or CD4>500 to 1000  Testing for viral hepatitis  Other: Toxoplasmosis, TB, STD screen, CMV?  Pneumococcal HAV, HBV vaccines (if not previous)  PCP prophylaxis (CD4<200)  1st Trimester inhaled pentamidine  2nd and 3rd Trimester TMP/SMX  Ultrasound both 1st and 2nd Trimester
    •  Mother to child transmission of HIV infection in the era of highly active antiretroviral therapy. CID. European Collaborative Study. 2005.  4625 mother-child pairs in prospective cohort (97-04)  In 1997-5% on HAART, by 2003 -92% on HAART  Total 1147 HAART, 654 (57%) started in 1st trimester, 39% prior to pregnancy  1998 only 29% undetectable, 50% in 2003  Mother-to-child-transmission 2.87 overall  From 2001-2003 0.99% (CI 0.32-2.3) 885 patients  Delivery (vaginal 410 (21%), instrument 35 (2%), elective C-section 1204 (61%) emergent C-section 306 (16%)  Entire cohort: Elective C section Adjusted OR (0.38 CI 0.24-0.61 O<0.001)  HAART era: 0.33 (0.11-0.94 p 0.40)
    •  With undetectable viral load (560 undetectable) OR 0.52 (CI 0.14-2.03 p=0.358)  Univariant Logistical Regression  Elective C section higher complication rate than vaginal  RECOMMENDATION: HIV>1000 copies/ml  Assess resistance (If adequate treatment duration)  Scheduled cesarean delivery at 38 weeks  Reasonable to offer elective C section-probably benefit but grossly underpowered (suggest further reduction of transmission to 0.5-1%)
    •  Collaboration of 7 European countries and US  1202 women with RNA<1000 at delivery  1% transmission rate 8/834 if on ART  9.8% transmission rate 36/368 untreated  C section OR 0.30 p=0.022)  Vaginal delivery 37/44 transmissions  Study did not factor risk of operative delivery to mother
    •  Cohort in France 1997-2010-received ART, not breastfeeding  IV ZDV used in 95.2% (11,538 deliveries)  Lack of ZDV 4.8% (554 deliveries)  If VL>1000 copies/ml-higher transmission without ZDV (7.5% vs. 2.9% P=0.01)  If VL<400, IV ZDV (0.6%, without 0%)  Conclusion IV ZDV for virological failure, not if effectively treated
    •  Deliver vaginally, start patient on ZDV/3TC LPV/r  Perform C section, start mother on IV ZDV, provide 6 weeks of ZDV and 3 doses of NVP to the child, discourage breast feeding  Perform C section, start mother on IV ZDV, provide 6 weeks of ZDV and 6 weeks of NVP to child, encourage breast feeding  Perform C section, start mother on IV ZDV, provide 4 weeks of ZDV and 4 weeks of NVP, discourage breast feeding
    •  Deliver vaginally, start patient on ZDV/3TC LPV/r  Perform C section, start mother on IV ZDV, provide 6 weeks of ZDV and 3 doses of NVP to the child, discourage breast feeding  Perform C section, start mother on IV ZDV, provide 6 weeks of ZDV and 6 weeks of NVP to child, encourage breast feeding  Perform C section, start mother on IV ZDV, provide 4 weeks of ZDV and 4 weeks of NVP, discourage breast feeding
    •  If woman is on ART & viral load>400 copies/mL- provide IV ZDV (AI)  If on ART, but RNA>1000, scheduled C section recommended (AI)  Scheduled C section is not recommended RNA<1000 BIII  Unclear if C section is beneficial for PROM  Avoid artificial rupture of membranes, operative delivery with forceps or fetal scalp electrodes  Breast-feeding not recommended in US  Different internationally  National Perinatal HIV Consultation and Referral Service at UCSF 1-888-448-8765
    •  comparison US British guideline WHO 39/1437 with birth defects comparable to baseline
    •  Giles, M. HIV and pregnancy: how to manage conflicting recommendations from evidence-based guidelines. AIDS. 2013; 27: 857-862.  Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf Accessioned 27 September 2013  Lahoz R, Noguera A, Rovira N, et al. Antiretroviral-related hematologic short-term toxicity in healthy infants: implications of the new neonatal 4-week zidovudine regimen. Pediatr Infect Dis J. Apr 2010;29(4):376-379.  Cooper ER, Charurat M, Mofenson L, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002; 29:484.  Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994; 331:1173.  http://en.wikipedia.org/wiki/Zidovudine Accessioned 1 Oct 2013  Hitti J, Andersen J, McComsey G, et al. Protease inhibitor-based antiretroviral therapy and glucose tolerance in pregnancy: AIDS Clinical Trials Group A5084. Am J Obstet Gynecol 2007; 196:331.e1.  Siberry GK, Williams PL, Mendez H, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS 2012; 26:1151.  Viganò A, Mora S, Giacomet V, et al. In utero exposure to tenofovir disoproxil fumarate does not impair growth and bone health in HIV-uninfected children born to HIV-infected mothers. Antivir Ther 2011; 16:1259.  Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral pregnancy registry international interim report for 1 Jan 1989 – 1 Jan 2010. Wilmington, NC: Registry coordinating center; 2010.
    •  Tarantal A, Castillo A, Ekert J, Bischofberger N, Martin R. Fetal and Maternal Outcome After Administration of Tenofovir to Gravid Rhesus Monkeys (Macaca mulatta) J Acquir Immune Defic Syndr. 2002;29(3):207.  Van Rompay KK, Brignolo LL, Meyer DJ, Jerome C, Tarara R, Spinner A, et al. Biological effects of short-term or prolonged administration of 9-[2-(phosphonomethoxy) propyl]adenine (tenofovir) to newborn and infant rhesus macaques. Antimicrob Agents Chemother. 2004 May;48(5):1469–87.  Van Rompay K, Durand-Gasselin L, Brignolo L, Ray A, Abel K, Cihlar T, et al. Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics, biological and virological effects. Antimicrob Agents Chemother. 2008;52(9):3144– 60.  http://www.uptodate.com/contents/prevention-of-hiv-transmission-during-breastfeeding-in- resource-limited-settings?source=see_link Accessioned 1 Oct 2013  http://www.uptodate.com/contents/antiretroviral-medications-in-pregnancy-entry-and-integrase- inhibitors?source=see_link Accessioned 1 oct 2013  McKeown D, Rosenvinge M, Donaghy S, Sharland M, Holt D, Cormack I, Hay P, SadiqS. High neonatal concentrations of raltegravir following transplacental transfer in HIV-1 positive women. AIDS. 2010: 2416-2418.  Carmela Pinnetti1*, Silvia Baroncelli2, Paola Villani3,, Massimo Fantoni1, Valerio Tozzi4, Andrea De Luca1,5,, Roberto Cauda1, Gianfranco Anzidei4, Maria Cusato3,, Mario Regazzi3, Marco Floridia2 and Enrica Tamburrini1. Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy Pinnetti C. et al. J Antimicrob Chemother. 2010.. 65: 2050-52.  Briand N, Warszawski J, Mandelbrot L, Dollfus C et al. Is intrapartum IV Zidovudine for prevention of mother-to-child HIV-1 transmission still useful in the combination antiretroviral therapy era? CID. 2013: 57: 903-914.
    •  Once daily fixed dose combinations  Tenofovir, lamivudine, emtricitabine and efavirenz in breast feeding  Goal to minimimize viral load  HIV transmission versus malnutrition  Concerns of poor water quality and mortality secondary to alternative causes  Duration ART-at least for duration of pregnancy and breast-feeding  Generally recommend lifelong therapy  Infants of breastfeeding mothers-nevirapine for at least 6 weeks