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HIV and Pregnancy
Updated August, 2009
Seble G. Kassaye, M.D, David A. Katzenstein, M.D
Globally, more than 20 million women of childbearing age are estimated to be HIV positive with the epidemic rapidly expanding in young women, of whom 95% are unaware of their infection. Thus millions of children are at risk of acquiring HIV infection during pregnancy, parturition and through breast-feeding. Rapid-testing in antenatal clinics, short-course and single dose antiretroviral treatments to mothers and infants and exclusive breast-feeding with early weaning are evolving interventions. In industrialized countries, treatment of pregnant women with potent antiretroviral therapies has resulted in a greater than 10-fold reduction in the vertical transmission of infection and pediatric AIDS. Highly active antiretroviral therapies (HAART) are effective in pregnancy and with certain exceptions, recommendations for treatment of adult and adolescent women are suitable during pregnancy. Additional strategies to reduce mother-to-child-transmission include active promotion of voluntary testing and counseling to identify HIV infection, antiretroviral therapy, elective caesarean section, prophylactic antiretrovirals to newborns and avoidance of breast-feeding. Rapid testing for detection of HIV-1 infection is now possible, and is recommended by Centers for Disease Control for pregnant women who go into labor without having had an HIV test (11, 42). Detection of disease, even at this late stage, would allow for interventions such as antiretroviral prophylaxis, minimization of invasive procedures intrapartum, and avoidance of breast feeding allowing further decreases in the incidence of mother to child transmission (MTCT) of HIV-1. Epidemiology of HIV in Women and Children Over 130,000 women had been diagnosed with AIDS in the U.S. by the end of June 2001, most of who were of reproductive age. In the absence of antiretroviral treatment about 30% of infected women will transmit infection to their babies during pregnancy, labor and delivery, or breastfeeding. Estimated fractions of intrauterine, intrapartum and post partum breast feeding transmission are approximately 5-10%, 10-15% and 10-12%, respectively. Although over 8,900 children in the U.S. were diagnosed with AIDS by the end of June 2001 (22), increased surveillance and antiretroviral treatment of pregnant women has led to a 10 year decline in the number of new pediatric AIDS cases in this country. In contrast, adolescent and adult women comprise 50% of estimated HIV infections worldwide and >500,000 infants are estimated to acquire HIV infection from their mothers each year (21). More women than males are infected with HIV in sub-Saharan Africa, with even higher proportions in females in the 15-24 year age category (28). Vertical HIV Transmission Although infants may acquire HIV throughout pregnancy, most in utero transmission occurs after the first trimester. Intrapartum transmission during labor and delivery accounts for the majority of vertical transmission with additional risk from breastfeeding in up to 15% of cases of vertical transmission (4, 30, 52). The risk of vertical transmission is influenced by viral load, antiretroviral treatment, mode of delivery, duration of ruptured membranes, breastfeeding, chorioamnionitis and fetal maturity, as well as illicit drug use (32, 49). Plasma HIV RNA levels are probably the single best predictor of the risk of transmission, however, there is no threshold below which lack of transmission can be assured (32, 13, 17, 50, 51). Transmission may also differ based on HIV-1 subtype, with subtype D HIV-1 infection being associated with a higher rate of transmission compared to subtype-A HIV-1 infection (70). Additionally, timing of transmission can vary by subtype, with subtype C HIV-1 vertical transmission more likely to occur in utero, than subtype A or D HIV-1 transmission (58). Effects of Pregnancy on HIV Disease Controlled studies in the United States and Europe have not demonstrated an effect of pregnancy on HIV disease progression (3, 12, 59, 63, 68). Some data do suggest, however, that pregnancy may accelerate HIV disease progression in resource-poor settings (23, 31, 54). Although a direct effect of pregnancy on HIV disease is uncertain, there is no doubt that physiologic changes associated with pregnancy can indirectly affect the kinetics of drug absorption, distribution, biotransformation, and elimination (57). These physiological changes may in some cases increase (prolonged gastrointestinal transit time and decreased plasma protein concentrations) or decrease (increased volume of distribution and increased blood flow to the liver and kidney) effective drug concentrations. However, specific recommendations on adjustments to antiretroviral drug dosing in pregnant women are not available. Effects of HIV on Outcome of Pregnancy HIV-infected women receiving antiretroviral therapy have a higher risk of pre-term delivery than uninfected women (8, 43, 45, 47, 15). Whether this risk is due to HIV disease, antiretroviral therapy, other correlated maternal risk factors (e.g. nutritional deficiencies, concomitant infections), or a combination of the above is not known. One large population-based survey in Uganda found that HIV-infected women had lower rates of conception and increased rates of spontaneous abortion (33). Safety of Antiretroviral Therapy During Pregnancy Data on the safety of antiretroviral drugs in pregnancy come from four sources: animal studies, anecdotal reports, patient clinical trials, and the Antiretroviral Pregnancy Registry (66). Antiretroviral drugs may be directly toxic to a fetus or may indirectly harm a fetus by through maternal toxicity. Nucleoside analog associated mitochondrial toxicity (including lactic acidosis and hepatic steatosis), anemia, and leukopenia can occur. Pharmacokinetics of antiretrovirals can be different during pregnancy. For example, saquinavir/ ritonavir (800mg/100mg BID) levels are higher during pregnancy than during the postpartum period (1), while nelfinavir levels are lower in the antepartum period (9) (14/17 meeting the targeted AUCO-12), than postpartum (10/11 met targeted AUCO-12). There is not an absolute correlation between drug levels and transmission, as despite detectable HIV-1 RNA > 400 copies/ ml in 3/14 women, there was only 1 documented case of vertical transmission in a small study of nelfinavir (1/23) in a woman treated for less than 3 weeks. Pregnancy may be complicated by protease inhibitor-induced gestational diabetes as found in PACTG 316, with an increased risk seen in pregnant women on a protease inhibitor containing regimen before or during the first trimester, less so in those initiated on such treatment during later time points (67). The possibility of unrecognized drug-related teratogenic effects as well as nausea and anorexia in the first trimester suggest that antiretroviral therapy may be interrupted or withheld, in pregnancy until the second trimester (24 weeks), unless there are maternal indications for treatment (e.g. symptomatic HIV disease, fewer than 200-300 CD4 cells, or plasma HIV-1 RNA levels > 55,000 copies/ml). It is generally recommended that women who become pregnant while receiving combination antiretroviral therapy continue treatment with close monitoring for pregnancy-related complications and drug toxicities (10, 17, 57). However, hydroxyurea, efavirenz, and delavirdine are contraindicated in pregnant women or in women planning to become pregnant. Hydroxyurea has carcinogenic and teratogenic potential. Efavirenz has been shown to cause anencephaly, anopthalmia, and micropthalmia in primates. Of 188 women with exposure to efavirenz in the first trimester, reported prospectively to the Pregnancy antiretroviral registry, birth defects were reported in 5. Independently, 4 cases of neural tube defects associated with first trimester exposure have also been reported (package insert Efavirenz 12/2004). Thus pregnancy testing, before the initiation of efavirenz is advised as well as strict adherence to both barrier and hormonal contraception by women with reproductive potential who are prescribed efavirenz. Delavirdine has demonstrated embryotoxicity in other animal models.). PACTG 1022 compared the safety of nelfinavir to nevirapine initiated between 10 and 30 weeks gestation, and showed evidence of increased hepatotoxicity, including one death, in the nevirapine arm in women with CD4+ lymphocyte counts greater than 250 cells per cu mm (5/14 subjects, p=0.04) (35). Recent case reports of fatal maternal lactic acidosis (accompanied by pancreatitis in 2 of 3 women) have led to recommendations to avoid the use of d4T-ddI-containing regimens in pregnancy (6, 46, 71). Pregnant women receiving NRTIs should have their hepatic enzymes, blood counts, and electrolytes monitored during the third trimester and those receiving protease inhibitors should be monitored for the development of hyperglycemia. Although the British HIV Association treatment guidelines state that physicians should consider monitoring lactate in women receiving NRTIs during pregnancy (7), this is likely to be impractical because the normal range for lactate levels in pregnant women is not known and it is difficult to obtain accurate, reproducible venous lactate results (66). Initial reports of a possible increased risk of ventricular septal defects due to Zidovudine (ZDV, AZT, Retrovir®, GlaxoSmithKline) were not confirmed in a large prospective study (44). NRTI exposure has been associated with mitochondrial dysfunction in the first few months of life even in uninfected infants (5, 45). However, the benefits of the reduced risk of transmission due to antiretroviral therapy far outweigh the extremely low risk of clinically apparent fetal mitochondrial toxicity (55, 66). Health care providers are requested to report infants with prenatal exposure to antiretroviral drugs to the Antiretroviral Pregnancy Registry, a project to collect observational data on exposure during pregnancy to assess the potential teratogenicity of these drugs (2). Efficacy of Antiretroviral Therapy During Pregnancy
Data on 419 mother-infant pairs enrolled in PACTG 076 revealed a 66% reduction
in perinatal HIV transmission, from 23% in the placebo group to 8% in the ZDV
group, when ZDV was administered during the 2nd and 3rd trimesters of pregnancy,
intrapartum, and to the neonate (three-part prophylaxis) (16,
61). Although most of the women enrolled in this particular
trial had low viral loads,
In the United States and Europe, ZDV prophylaxis has been superseded by highly
active antiretroviral therapy (HAART). Treatment with a combination of ZDV and
Onen NF, et al. Effect of Postpartum HIV Treatment Discontinuation on Long-Term Maternal Outcome. J Int Assoc Physicians AIDS Care (Chic Ill). 2008 Sep 23. [Epub ahead of print] Prophylaxis Regimens in Resource-Limited Settings In resource-limited settings, less expensive, shorter prophylaxis regimens have been studied providing guidance for the management of pregnant women in regions where HAART regimens are not available, as well as insight into the dynamics of maternal-to-child transmission that are particularly relevant when HIV infection is identified late in pregnancy or at parturition. In a Thailand study initiating treatment with ZDV of the mother at 28 weeks and extending the treatment in the neonate for 6 weeks was associated with a significantly lower rate of vertical transmission of 4.1% (40). Similarly, the Petra study in Africa showed that earlier initiation of ZDV-3TC at 36 weeks with continued treatment of the infant post-partum for 7 days decreased transmission by more than 60% compared to placebo, but sustained efficacy in prevention of transmission was more likely in infants who were not breastfed (25). More recent data from studies in Thailand show transmission rates of 4.6% when ZDV treatment was initiated in the mother between 34-36 weeks gestation and continued through delivery, with the addition a single dose of nevirapine to the mother, and prophylaxis in the infant using a single dose of nevirapine between 48 and 72 hours of life in addition to ZDV for 4 weeks (14). Earlier administration of ZDV starting close to 28 weeks of gestation with an intrapartum single dose of nevirapine to the mother, followed by a single dose of nevirapine and a week of ZDV to the infant resulted in a further decrease in vertical transmission to less than 2% (41).
Another study in Uganda showed that a single oral dose of nevirapine given at
the onset of labor combined with a single oral dose given to the neonate reduced
transmission by 50% in treatment naïve women when compared to an equivalent
dosing schedule of ZDV (34), with the greatest difference between the two
interventions seen in women with HIV-1 RNA levels (>50,000 copies/ ml) and lower
CD4+ t-lymphocyte counts (<200 per cu mm). However, approximately 20%-44% of the
women receiving nevirapine were found to have genotypic resistance to each of
the NNRTIs eight to ten weeks following their dose of
Treatment Recommendations The Public Health Service Task Force has a series of recommendations for treating pregnant women that take into account the time of presentation with respect to conception and delivery (Table 1) (57). Women whose immunologic or virologic status requires treatment, or who have plasma HIV RNA levels >1,000 copies/ml should receive HAART including ZDV. In pregnant women with plasma HIV RNA levels <1,000 copies/ml, perinatal transmission is reduced from about 10% without treatment to 1% in women receiving ZDV prophylaxis (36). Therefore, even women whose virologic and immunologic status does not require treatment should be offered therapy, such as ZDV monotherapy or a standard HAART regimen, to prevent perinatal transmission. Dual nucleoside regimens have also been used in this setting, but may lead to the development of NRTI resistance, and should be viewed with caution Antiretroviral treatment can be discontinued postnatally in women for whom treatment was used only to prevent perinatal transmission. Because most perinatal transmission occurs during late pregnancy and delivery, HIV-infected women may consider withholding therapy during the first 10 weeks of gestation when nausea and vomiting may interfere with adherence, tolerance, and bioavailability and increase the risk of drug resistance. In addition, definitive safety data are for most antiretroviral drugs during the first trimester are still pending.
Treatment-naïve women presenting during labor should be offered one of the
following four regimens: (i) a single dose of
Infants born to mothers who have received no antiretroviral treatment at any time during pregnancy or intrapartum are candidates for treatment for six weeks of ZDV after birth. ZDV should be started within 6 to 12 hours after birth and may be used in combination with other antiretroviral drugs if the mother is suspected to have ZDV-resistant virus. As in other post-exposure prophylaxis situations, some physicians would institute HAART both to treatment-naive women presenting during labor and to infants born to mothers who may or may not have received intrapartum antiretroviral drugs. Guideline: Aberg JA, et al. Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2009;49:651-681. Guideline: Guidelines for diagnosis and treatment of HIV/AIDS. Taiwan CDC, Jan 2008.
Guideline:
Public Health Service Task Force Recommendations for Use
of Antiretroviral Drugs in Pregnant HIG-Infected Women for Maternal Health and
Interventions to Reduce Perinatal HIV Transmission in the United States. July 8,
2008. http://aidsinfo.nih.gov/
Vertical Transmission of Drug-Resistant HIV Antiretroviral drug resistance testing should be obtained in all pregnant women with detectable viremia who are receiving antiretroviral therapy or in pregnant women residing in areas with significant rates of primary HIV resistance who are about to start antiretroviral therapy (65, 71). Limited data suggest that ZDV-resistant isolates are more likely to be transmitted than ZDV-susceptible isolates (69) and a recent study of ARV naïve pregnant women in St Louis found evidence of NNRTI resistant virus in 2 of 17 pregnant women, consistent with an increasing rate of acquisition of and transmission of NNRTI resistance. In heavily treated women with persistent viremia, it is important to consider drugs received in the past, the current drug regimen, and the available options for post-partum prophylaxis of the infant. For example, if a woman previously developed virologic failure while receiving an NNRTI or 3TC, then it is unlikely that an NNRTI or 3TC will be effective at suppressing maternal viremia. However, these drugs may be useful for post-partum prophylaxis if resistance to these drugs is not evident in maternal virus near delivery. Although efavirenz is contraindicated during the first trimester, it may be used later in pregnancy, particularly if it is needed to treat a drug-resistant maternal strain (66). Optimal antiretroviral prophylaxis of the infant born to a woman with drug-resistant HIV should be determined in consultation with pediatric infectious diseases specialists and should be based on the levels of maternal viremia and resistance tests done during pregnancy. Cesarean Delivery Studies from the United States and Europe have shown that in the absence of antiretroviral therapy, elective cesarean section reduces the risk of perinatal HIV transmission from about 20% to 10% or lower (26, 64). In the presence of ZDV chemoprophylaxis, perinatal HIV transmission is reduced from 4-7% with regular delivery to 1-2% with cesarean delivery (26, 64). Whether elective cesarean delivery offers any benefit to the infants of women receiving HAART who have low or undetectable plasma HIV RNA levels is not known. Plasma HIV RNA levels should be checked at 34-36 weeks gestation and options for mode of delivery should be discussed at that time. Based on the low risk associated with low plasma HIV RNA levels, the American College of Obstetrics and Gynecology has chosen 1,000 copies/ml as the threshold above which to recommend scheduled cesarean delivery as an adjunct for preventing perinatal HIV transmission (57). Elective cesarean delivery should be performed at 38-39 weeks gestation or at the onset of labor. The benefit of a slightly reduced risk of HIV transmission should be balanced against the increased risk of post-operative complications associated with cesarean delivery. Cesarean delivery should be accompanied by intravenous ZDV administered three hours prior to the surgery followed by six weeks of ZDV therapy for the neonate. There are not enough data to evaluate the role of cesarean delivery in women in labor or after membrane rupture. This situation should be evaluated on a case-by-case basis, taking into account the duration of membrane rupture, progress of labor, plasma HIV RNA levels, the woman's current antiretroviral therapy regimen and other clinical factors. The public health service guidelines have been recently updated with respect to four scenarios: (A) HIV-infected women presenting late in pregnancy not receiving antiretroviral therapy and in whom virus load data are not expected to be available before delivery, (B) HIV-infected women who initiated prenatal care early in 3rd trimester, are receiving HAART, and have had an initial virologic response, but have RNA levels that are >1,000 copies/ml at 36 weeks gestation, (C) HIV-infected women on HAART with undetectable plasma HIV RNA levels at 36 weeks gestation, (D) HIV-infected women who have elected scheduled cesarean section but present in early labor or shortly after rupture of membranes (57). Breastfeeding Breastfeeding appears to confer an additional risk above and beyond the risk of pregnancy and parturition proportional to the duration of breastfeeding (20, 24, 53, 54). In settings in which alternatives to breastfeeding are available, safe, and affordable, formula feeding is recommended. Chasela C, et
al.
Both maternal HAART and daily infant nevirapine are
effective in reducing HIV-1 transmission during breastfeeding in a randomized
trial in Malawi: 28 week results of the Breastfeeding, Antiretroviral and
Nutrition (BAN) Study. 5th IAS Conference on HIV Treatment,
Pathogenesis and Prevention, Cape Town, abstract WeLBC103, 2009. Tables and Figures
Table 1.Clinical
Scenarios and Recommendations for the Use of Antiretroviral Drugs to Reduce
Perinatal HIV Transmission
REFERENCES 1. Acosta EP, Bardeguez A, Zorrilla CD, Van Dyke R, Hughes MD, Huang S, Pompeo L, Stek AM, Pitt J, Watts DH, Smith E, Jimenez E, Mofenson L. Pharmacokinetics of saquinavir plus low-dose ritonavir in human immunodeficiency virus-infected pregnant women. Antimicrob Agents Chemother 2004; 48:430-6. [PubMed] 2. Antiretroviral Pregnancy Registry 2002. internet access: www.APRegistry.com, tel:800-258-4263., 2002. [PubMed] 3. Berrebi A, Kobuch WE, Puel J, Tricoire J, Herne P, Grandjean H, Pontonnier G. Influence of pregnancy on human immunodeficiency virus disease. Eur J Obstet Gynecol Reprod Biol 1990; 37:211-7. [PubMed] 4. Bertolli J, St Louis ME, Simonds RJ, Nieburg P, Kamenga M, Brown C, Tarande M, Quinn T, Ou CY. Estimating the timing of mother-to- child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire. J Infect Dis 1996; 174:722-6. [PubMed] 5. Blanche S, Tardieu M, Rustin P, Slama A, Barret B, Firtion G, Ciraru-Vigneron N, Lacroix C, Rouzioux C, Mandelbrot L, Desguerre I, Rotig A, Mayaux MJ, Delfraissy JF. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 1999; 354:1084-9. [PubMed] 6. Bristol-Myers Squibb Company. Bristol-Myers warns of AIDS drugs' use. AIDS Read 2001; 11:82 [PubMed] 7. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Med 2001; 2:276-313. [PubMed] 8. Brocklehurst P, French R. The association between maternal HIV infection and perinatal outcome: a systematic review of the literature and meta-analysis. Br J Obstet Gynaecol 1998; 105:836-48. [PubMed] 9. Bryson Y, Stek A, Mirochnick M, et al. Pharmakokinetics, antiviral activity, and safety of nelfinavir (NFV) with ZDV/3TC in pregnant HIV infected women and their infants: PACTG 353 Cohort 2., 9th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, 2002. Vol. Abs. 795W. [PubMed] 10. Bucceri AM, Somigliana E, Matrone R, Ferraris G, Rossi G, Grossi E, Vignali M. Combination antiretroviral therapy in 100 HIV-1-infected pregnant women. Hum Reprod 2002; 17:436-41. [PubMed] 11. Bulterys M, Jamieson DJ, O'Sullivan MJ, et al. Performance of rapid HIV-1 testing at labor and delivery: A multicenter study, 11th Conference on retroviruses and opportunistic infections, San Francisco, CA, 2004. Vol. Abs. 95. [PubMed] 12. Burns DN, Landesman S, Minkoff H, Wright DJ, Waters D, Mitchell RM, Rubinstein A, Willoughby A, Goedert JJ. The influence of pregnancy on human immunodeficiency virus type 1 infection: antepartum and postpartum changes in human immunodeficiency virus type 1 viral load. Am J Obstet Gynecol 1998; 178:355-9. [PubMed] 13. Cao Y, Krogstad P, Korber BT, Koup RA, Muldoon M, Macken C, Song JL, Jin Z, Zhao JQ, Clapp S, Chen IS, Ho DD, Ammann AJ. Maternal HIV-1 viral load and vertical transmission of infection: the Ariel Project for the prevention of HIV transmission from mother to infant. Nat Med 1997; 3:549-52. [PubMed] 14. Chalermchokcharaoenkit A, Asavapiriyanont S, Teeraratkul A, et al. Combination short-course zidovudine plus 2-dose nevirapine for prevention of mother-to-child transmission: safety, tolerance, transmission, and resistance results., 11th Conference on Retroviruses and Opportunistic Infections., San Francisco, CA, 2004. Vol. Abs. 96. [PubMed] 15. Combination antiretroviral therapy and duration of pregnancy. AIDS 2000; 14:2913-20. [PubMed] 16. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, 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; 331:1173-80. [PubMed] 17. Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, Hayani K, Handelsman E, Smeriglio V, Hoff R, Blattner W; Women and Infants' Transmission Study Group. 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; 29:484-94. [PubMed] 18. Cunningham CK, Chaix ML, Rekacewicz C, Britto P, Rouzioux C, Gelber RD, Dorenbaum A, Delfraissy JF, Bazin B, Mofenson L, Sullivan JL. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis 2002; 186:181-8. [PubMed] 19. Dancis J, Lee JD, Mendoza S, Liebes L. Transfer and metabolism of dideoxyinosine by the perfused human placenta. J Acquir Immune Defic Syndr 1993; 6:2-6. [PubMed] 20. Datta P, Embree JE, Kreiss JK, Ndinya-Achola JO, Braddick M, Temmerman M, Nagelkerke NJ, Maitha G, Holmes KK, Piot P, et al. Mother-to-child transmission of human immunodeficiency virus type 1: report from the Nairobi Study. J Infect Dis 1994; 170:1134-40. [PubMed] 21. De Cock KM, Fowler MG, Mercier E, de Vincenzi I, Saba J, Hoff E, Alnwick DJ, Rogers M, Shaffer N. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283:1175-82. [PubMed] 22. Department of Health And Human Services, Public Health Service, Centers for Disease Control and Prevention. U.S. HIV and AIDS cases reported through December 2001. HIV AIDS Surveillance Report. 13(2). [PubMed] 23. Deschamps MM, Pape JW, Desvarieux M, Williams-Russo P, Madhavan S, Ho JL, Johnson WD Jr. A prospective study of HIV-seropositive asymptomatic women of childbearing age in a developing country. J Acquir Immune Defic Syndr 1993; 6:446-51. [PubMed] 24. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Lancet 2000; 355:451-5. [PubMed] 25. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet 2002; 359:1178-86. [PubMed] 26. Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial. The European Mode of Delivery Collaboration. Lancet 1999; 353:1035-9 [PubMed] 27. Eshleman SH, Guay LA, Mwatha A, et al. Characterization of nevirapine resistance mutations in women with subtype A vs. D HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012). J Acquir Immune Defic Syndr 2004; 35:126-30. [PubMed] 28. Executive Summary: 2004 Report on the global AIDS epidemic. Vol. 2004: (UNAIDS) Joint United Nations Programme on HIV/AIDS, 2004. [PubMed] 29. Fiscus SA, Adimora AA, Schoenbach VJ, McKinney R, Lim W, Rupar D, Kenny J, Woods C, Wilfert C, Johnson VA. Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina. J Infect Dis 1999; 180:99-105. [PubMed] 30. Fowler MG. Update: transmission of HIV-1 from mother to child. Curr Opin Obstet Gynecol 1997; 9:343-8. [PubMed] 31. French R, Brocklehurst P. The effect of pregnancy on survival in women infected with HIV: a systematic review of the literature and meta-analysis. Br J Obstet Gynaecol 1998; 105:827-35. [PubMed] 32. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J, Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med 1999; 341:394-402. [PubMed] 33. Gray RH, Wawer MJ, Serwadda D, Sewankambo N, Li C, Wabwire-Mangen F, Paxton L, Kiwanuka N, Kigozi G, Konde-Lule J, Quinn TC, Gaydos CA, McNairn D. Population-based study of fertility in women with HIV-1 infection in Uganda. Lancet 1998; 351:98-103. [PubMed] 34. Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D, Mmiro F, Jackson JB. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999; 354:795-802. [PubMed] 35. Hitti J, Frenkel LM, Stek AM, et al. Maternal toxicity with continuous nevirapine in pregnancy. J Acquir Immune Defic Syndr 2004; 36:772-776. [PubMed] 36. Ioannidis JP, Abrams EJ, Ammann A, Bulterys M, Goedert JJ, Gray L, Korber BT, Mayaux MJ, Mofenson LM, Newell ML, Shapiro DE, Teglas JP, Wilfert CM. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml. J Infect Dis 2001; 183:539-45. [PubMed] 37. Jackson JB, Becker-Pergola G, Guay LA, Musoke P, Mracna M, Fowler MG, Mofenson LM, Mirochnick M, Mmiro F, Eshleman SH. Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. AIDS 2000; 14:F111-5. [PubMed] 38. Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med 2004; 351:229-40. [PubMed] 39. Kantor R, Lloyd R, Shafer R, et al. Comparison of mother-to-child transmission (MTCT) and genotypic resistance in HIV-1 subtypes A, C, and D after single dose nevirapine (sd-NVP) in Africa., 9th Conference on Retroviruses and Opportunistic Infections., Seattle, WA, 2002. Vol. Abs. 801-W. [PubMed] 40. Lallemant M, Jourdain G, Le Coeur S, Kim S, Koetsawang S, Comeau AM, Phoolcharoen W, Essex M, McIntosh K, Vithayasai V. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators. N Engl J Med 2000; 343:982-91. [PubMed] 41. Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004; 351:217-28. [PubMed] 42. Lampe M, Branson B, Paul S, et al. Rapid HIV-1 antibody testing during labor and delivery for women of unknown HIV status: A practical guide and model protocol. Vol. 2004: Division of HIV/AIDS, Centers for Disease Control, 2003. [PubMed] 43. Leroy V, Ladner J, Nyiraziraje M, De Clercq A, Bazubagira A, Van de Perre P, Karita E, Dabis F. Effect of HIV-1 infection on pregnancy outcome in women in Kigali, Rwanda, 1992-1994. Pregnancy and HIV Study Group. AIDS 1998; 12:643-50. [PubMed] 44. Lipshultz SE, Easley KA, Orav EJ, Kaplan S, Starc TJ, Bricker JT, Lai WW, Moodie DS, Sopko G, McIntosh K, Colan SD. Absence of cardiac toxicity of zidovudine in infants. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group. N Engl J Med 2000; 343:759-66. [PubMed] 45. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, Berrebi A, Benifla JL, Burgard M, Lachassine E, Barret B, Chaix ML, Bongain A, Ciraru-Vigneron N, Crenn-Hebert C, Delfraissy JF, Rouzioux C, Mayaux MJ, Blanche S; Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study Group. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001; 285:2083-93. [PubMed] 46. Marcus K, Truffa M, Boxwell D, Toerner J. Recently identified adverse events secondary to NRTI therapy in HIV-infected individuals: cases from the FDA's adverse event reporting system (AERS). 9th Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 2002. [PubMed] 47. Martin R, Boyer P, Hammill H, Peavy H, Platzker A, Settlage R, Shah A, Sperling R, Tuomala R, Wu M. Incidence of premature birth and neonatal respiratory disease in infants of HIV-positive mothers. The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus Infection Study Group. J Pediatr 1997; 131:851-6. [PubMed] 48. Martinson N, Morris L, Gray G, et al. HIV resistance and transmission following single-dose nevirapine in a PMTCT cohort., 11th Conference on Retroviruses and Opportunistic Infections., San Francisco, CA, 2004. Vol. Abs. 38. [PubMed] 49. Maternal viral load and vertical transmission of HIV-1: an important factor but not the only one. The European Collaborative Study. AIDS 1999; 13:1377-85. [PubMed] 50. Mayaux MJ, Dussaix E, Isopet J, Rekacewicz C, Mandelbrot L, Ciraru-Vigneron N, Allemon MC, Chambrin V, Katlama C, Delfraissy JF, Puel J. Maternal virus load during pregnancy and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohort studies. SEROGEST Cohort Group. J Infect Dis 1997; 175:172-5. [PubMed] 51. Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA 3rd, Whitehouse J, Moye J Jr, Reichelderfer P, Harris DR, Fowler MG, Mathieson BJ, Nemo GJ. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med 1999; 341:385-93. [PubMed] 52. Mofenson LM. U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. MMWR Recomm Rep 2002; 51:1-38; quiz CE1-4. [PubMed] 53. Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J, Mwatha A, Ndinya-Achola J, Bwayo J, Onyango FE, Hughes J, Kreiss J. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000; 283:1167-74. [PubMed] 54. Nduati R, Richardson BA, John G, Mbori-Ngacha D, Mwatha A, Ndinya-Achola J, Bwayo J, Onyango FE, Kreiss J. Effect of breastfeeding on mortality among HIV-1 infected women: a randomised trial. Lancet 2001; 357:1651-5. [PubMed] 55. Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. J Acquir Immune Defic Syndr 2000; 25:261-8. [PubMed] 56. Patterson TA, Binienda ZK, Newport GD, Lipe GW, Gillam MP, Slikker W Jr, Sandberg JA. Transplacental pharmacokinetics and fetal distribution of 2', 3'-didehydro-3'-deoxythymidine (d4T) and its metabolites in late-term rhesus macaques. Teratology 2000; 62:93-9. [PubMed] 57. Recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health, and interventions to reduce perinatal HIV-1 transmission in the United States. Vol. 2004, http://www.aidsinfo.nih.gov/guidelines/perinatal/PER_062304.pdf: Public Health Service Task Force, 2004. [PubMed] 58. Renjifo B, Gilbert P, Chaplin B, Vannberg F, Mwakagile D, Msamanga G, Hunter D, Fawzi W, Essex M. Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D. AIDS 2004; 18:1629-36. [PubMed] 59. Saada M, Le Chenadec J, Berrebi A, Bongain A, Delfraissy JF, Mayaux MJ, Meyer L. Pregnancy and progression to AIDS: results of the French prospective cohorts. SEROGEST and SEROCO Study Groups. AIDS 2000; 14:2355-60. [PubMed] 60. Sandberg JA, Slikker W Jr. Developmental pharmacology and toxicology of anti-HIV therapeutic agents: dideoxynucleosides. Faseb J 1995; 9:1157-63. [PubMed] 61. Sperling RS, Shapiro DE, Coombs RW, Todd JA, Herman SA, McSherry GD, O'Sullivan MJ, Van Dyke RB, Jimenez E, Rouzioux C, Flynn PM, Sullivan JL. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1996; 335:1621-9. [PubMed] 62. Stiehm ER, Lambert JS, Mofenson LM, Bethel J, Whitehouse J, Nugent R, Moye J Jr, Glenn Fowler M, Mathieson BJ, Reichelderfer P, Nemo GJ, Korelitz J, Meyer WA 3rd, Sapan CV, Jimenez E, Gandia J, Scott G, O'Sullivan MJ, Kovacs A, Stek A, Shearer WT, Hammill H. Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185. J Infect Dis 1999; 179:567-75. [PubMed] 63. Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe. The European Collaborative Study. Br J Obstet Gynaecol 1998; 105:704-9. [PubMed] 64. The International Perinatal HIV Group. The Mode of Delivery and the Risk of Vertical Transmission of Human Immunodeficiency Virus Type 1 -- A Meta-Analysis of 15 Prospective Cohort Studies. N Engl J Med 1999; 340:977-987 [PubMed] 65. US Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents., 2002. [PubMed] 66. Watts DH. Management of human immunodeficiency virus infection in pregnancy. N Engl J Med 2002; 346:1879-91. [PubMed] 67. Watts DH, Balasubramanian R, Maupin RT Jr, Delke I, Dorenbaum A, Fiore S, Newell ML, Delfraissy JF, Gelber RD, Mofenson LM, Culnane M, Cunningham CK; PACTG 316 Study Team. Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316. Am J Obstet Gynecol 2004; 190:506-16. [PubMed] 68. Weisser M, Rudin C, Battegay M, Pfluger D, Kully C, Egger M. Does pregnancy influence the course of HIV infection? Evidence from two large Swiss cohort studies. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17:404-10. [PubMed] 69. Welles SL, Pitt J, Colgrove R, McIntosh K, Chung PH, Colson A, Lockman S, Fowler MG, Hanson C, Landesman S, Moye J, Rich KC, Zorrilla C, Japour AJ. HIV-1 genotypic zidovudine drug resistance and the risk of maternal--infant transmission in the women and infants transmission study. The Women and Infants Transmission Study Group. AIDS 2000; 14:263-71. [PubMed] 70. Yang C, Li M, Newman RD, Shi YP, Ayisi J, van Eijk AM, Otieno J, Misore AO, Steketee RW, Nahlen BL, Lal RB. Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission. AIDS 2003; 17:1667-74. [PubMed] 71. Yeni PG, Hammer SM, Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Volberding PA. Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel. JAMA 2002; 288:222-35. [PubMed]
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