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AIDS:
Clinical Science

An effective and safe protocol involving zidovudine and caesarean section to reduce vertical transmission of HIV-1 infection

Grosch-Wörner, llsea; Schäfer, Axelb; Obladen, Michaelc; Maier, Rolf F.c; Seel, Karena; Feiterna-Sperling, Corneliaa; Weigel, Ralfa

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Author Information

From the aDepartment of Pediatrics, the bDepartment of Obstetrics and the cDepartment of Neonatology, Charité Virchow-Klinikum Berlin, Germany.

Requests for reprints to Dr Ilse Grosch-Wörner, Department of Pediatrics, Charité Virchow-Klinikum, D-13 353 Berlin, Augustenburger Platz 1, Germany.

Received: 26 June 2000;

revised: 24 August 2000; accepted: 4 September 2000.

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Abstract

Objective: To investigate zidovudine prophylaxis with caesarean section to reduce mother-to-infant HIV transmission.

Interventions: Elective caesarean section before labour, usually at 36–38 weeks of gestation, plus a short oral course of zidovudine, normally starting at week 32, intravenous zidovudine before caesarean section and for 10 days for the neonate (the reduced Berlin regimen).

Results: Of 179 mother–infant pairs 104 received no antiretroviral prophylaxis or therapy (control group), 48 received the reduced Berlin prophylaxis regimen, 18 received combination therapy and nine received only part of the prophylaxis regimen. Of the antiretroviral group, 68 were delivered by elective caesarean section. The HIV transmission rate was zero in the antiretroviral group [95% confidence interval (CI) 0–4.7] and 12.6% (6.4–19.0) in the control group. The reduction in vertical transmission was 90% for the Berlin regimen, with an 80 and 70% reduction in risk associated with antiretroviral treatment and caesarean section, respectively. Maternal CD4 cell count but not viral load had some confounding effect on the reduction in risk attributed to caesarean section and the prophylactic regimen. Neonatal haematological abnormalities associated with antiretroviral intervention lasted for up to 7 weeks. Weight and length, although significantly lower at birth, were normal by 6–8 weeks.

Conclusion: A much reduced three-arm regimen of zidovudine prophylaxis in combination with caesarean section before labour is highly effective in reducing the risk of vertical HIV transmission and is safe for the infant.

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Introduction

Early results from some, but not all, observational studies suggested a possible beneficial effect of delivery by caesarean section on the rate of vertical HIV transmission [1–5]. Recent results of the Randomized Mode of Delivery Trial [6,7] and a meta-analysis of all prospective HIV perinatal studies in Europe and the United States [8] have confirmed these observations.

The use of zidovudine (ZDV) prophylaxis by an HIV-infected woman during pregnancy and delivery and by her neonate for 6 weeks has also been shown to reduce the risk of transmission substantially [9]. The effect of antiretroviral prophylaxis is likely to be independent from that of a caesarean section. A combination of the two interventions could, in theory, achieve transmission rates below 1% in the absence of breastfeeding [7,8,10–13].

The ZDV regimen evaluated in the 076 trial, which is commonly used in clinical practice, consisted of three arms: an antepartum part starting between 14 and 34 weeks of gestation, an intrapartum arm with intravenously administered ZDV and a 6 week postexposure chemoprophylaxis for the neonate [9]. However, it is not known whether all three arms of this regimen contributed to the reduction in risk. Subsequently modifications to this prolonged regimen have been evaluated in observational cohorts, focusing mainly on the peripartum period. In the absence of breastfeeding, most transmission occurs during or just prior to delivery and the postexposure neonatal component could therefore be of major importance [14–18].

In a trial in Thailand, ZDV given orally from 36 weeks of gestation until delivery without neonatal prophylaxis was still found to be effective in reducing the HIV transmission risk [19] in a non-breastfeeding population. Similar results with similar regimens in breastfeeding populations were reported from trials in Abidjan, Côte d'Ivoire [20] and in Côte d'lvoire and Burkina Faso [21]. In all three trials a short-course of ZDV for the mother was safe, well tolerated and decreased mother-to-child HIV transmission, but none of the trials provided evidence that a simultaneous postexposure prophylaxis for the neonate would have been equally or more effective. The importance of postnatal ZDV prophylaxis was highlighted in an observational study in New York [22]. This study included mothers who had received the full ACTG 076 regimen, and women who had booked late or received no antenatal care, were not offered or were refused treatment. The effect of ZDV prophylaxis was most pronounced when treatment was begun antenatally. However, ZDV given only to the infant within the first 48 hours of life was still found to reduce the risk of transmission significantly; this would lend support for postexposure prophylaxis.

We evaluated the efficacy and safety of a reduced regimen of ZDV prophylaxis, starting at 32 to 34 weeks of gestation, with an elective caesarean section at 36 weeks of gestation and 10 days intravenous ZDV for the infant. This regimen was offered only to pregnant women not at increased risk of obstetrical complications and who had no clinical indication for antiretroviral therapy [23–25].

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Methods

Since July 1985, HIV-infected pregnant women and their children in Berlin have been enrolled in a prospective HIV perinatal study and followed according to a standard protocol.

The prospective evaluation of the pregnant women included clinical and obstetrical investigations and assessment of haematological (complete blood count), immunological (Iymphocyte phenotyping with absolute and percentage CD4 cell count), CD8 cell (absolute count and percentage) and virological (viral load) parameters. Hepatitis C infection and route of HIV infection were recorded. Infants were followed up to 18–24 months of age to ensure HIV infection status was definitively determined. Infants were seen at birth or 1 day after, at 7–9 days, at 15–17 days, 4 and 7 weeks and 4, 6, 12, 18 and 24 months. Neonatal information collected at birth included sex, detailed clinical investigation, gestational age, weight, length, head circumference, structural birth defects, withdrawal symptoms, duration of hospitalization. Further infant information collected at later check-ups included haematological parameters (haemoglobin concentration, haematocrit, white blood cell count, absolute neutrophil count, platelet count, reticulocytes), biochemical parameters (bilirubin, alanine and aspartate aminotransferase, γ-glutamate aminotransferase, alkaline phosphatase, serum creatinine concentration, electrolytes), immunological (IgG, lgA, IgM, absolute and percentage CD4 and CD8 cell counts) and HIV-1 virus load. From 1995, viral load was assessed using NASBA method (Organon Technika, Durham, North Carolina, USA), the lower limit for detection was initially 4000 copies/ml, changing to 800 copies/ml in October 1997 and to 400 copies/ml in November 1997.

All HIV-infected pregnant women were offered an elective caesarean section, performed prior to the onset of labour in gestation week 36+0, and were advised not to breastfeed. After the results of the ACTG 076 study became available [9], antiretroviral prophylaxis with ZDV was also offered to all women. The regimen used was oral ZDV 100 mg five times daily starting at 32–34 weeks of pregnancy; 200 mg ZDV intravenously before elective caesarean section, and intravenous ZDV to the neonate postnatally for 10 days, 1.3 mg/kg every 6 h beginning 6 h after delivery. Each woman gave written informed consent for herself and (with the father of the infant, when possible) for her infant. The study protocol was approved by the institutional ethics committee.

To avoid contamination of the fetal mouth during caesarean section, the uterus was opened through the lower uterine segment by a careful incision leaving the membranes intact. These were prepared under immediate haemostasis. The membranes were detached from the inner surface of the lower uterine segment and the cervix until the fetal head was lifted through the incision within the membranes. Usually the membranes broke at that moment and the fetal mouth and nasal cavity were immediately aspirated with a bulb syringe.

Infants were defined as not infected if in at least two separate blood samples there was no evidence for HIV according to qualitative and quantitative polymerase chain reaction (Reverse-transcription PCR, Amplicor Monitor, Roche Diagnostic Systems, Branchburg, New Jersey, USA) and nucleic acid sequence-based amplification (NASBA) of plasma (Organon Technika), and in the absence of HlV-related symptoms. Infants were classified as definitively HIV negative if they became antibody negative [26]. For deliveries before 1995, viral load was determined on frozen samples.

To assess the short-term safety of antiretroviral prophylaxis for the neonates, they were divided into a case group and a comparison group. The case group consisted of mother–infant pairs that had the reduced Berlin prophylaxis regimen (group 1). The control group included mothers and their infants who did not receive any antiretroviral prophylaxis. For the evaluation of safety, the HlV-infected children of the control group are excluded from the evaluation. In the present analysis, information collected up to 6 months of age was included.

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Statistical analysis

Medians and quartiles are presented for the descriptive analysis. In addition, the distribution of some variables are presented in box-whisker plots with minimum and maximum values. To test for differences, the Mann–Whitney test for medians and the chi square test for relative frequencies were used. The respective tests were calculated using SPSS software (9.0 for windows SPSS, Inc., Chicago, Illinois, USA ). All P values are two-tailed. Statistical significance was defined as P < 0.05. Weight and height of the infants are presented by median and quartiles in comparison to values of infants born to HIV-negative mothers [27]

Logistic regression was performed using LogXact to assess the effects of elective caesarean section, therapy regimen, viral load, CD4 cell count on vertical transmission. Therapy was categorized as three groups: no therapy, Berlin regimen and other regimen. Each of the variables was looked at in turn in univariate analyses, then confounding effects of viral load and CD4 cell count on elective caesarean section and therapy regimen were considered. Finally, the estimates for elective caesarean section and therapy were adjusted by way of multivariate analysis. Throughout, log10 viral load was used and absolute CD4 cell count was categorized as > 500, 200–500 and < 200 × 106 cells/l.

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Results

A total of 179 mother–infant pairs, including one pair of twins, were enrolled during the study period from July 1985 to July 1999. Within this cohort, 104 mothers delivered 104 neonates before the introduction of routine ZDV prophylaxis and represent, therefore, the control group (no antiretrovirals). A total of 91 of the infants in this control group were not infected and were used as the control group for the assessments of safety.

The study group consisted of 75 mother–infant pairs with 76 infants. Of these, 48 mothers and 49 neonates received the reduced Berlin prophylaxis regimen (group 1). The median duration of the maternal ZDV prophylaxis was 15.5 days [25–75% interquartile range (IQR) 13–30). A further 18 women received combination antiretroviral therapy (group 2), usually ZDV and lamivudine (n = 10), with nevirapine for four and protease inhibitors in another four. The median duration of the combination therapy was 187 days (70–241). All women received 200 mg/kg ZDV intravenously before caesarean section and all 18 neonates were given 10 days intravenous ZDV as described. In the remaining nine mother–infant pairs, ZDV prophylaxis was incomplete (group 3): three mothers received no antenatal ZDV and of their three infants one received 10 days intravenous ZDV and two received ZDV for 6 weeks orally; two mothers received only antepartum prophylaxis and their infants received 6 weeks ZDV orally. In four cases the mothers received the antepartum prophylaxis but the infants did not.

There have been changes over time in the characteristics of HIV-infected pregnant women, and this is reflected in the comparison between the women who received and those who did not receive antiretrovirals (Table 1). Heterosexual acquisition of infection has become more common, and this was the most important risk factor for acquisition in the patients that had received antiretroviral therapy. The confirmation of the effect of elective caesarean section has resulted in a higher percentage of women in the antiretroviral group being delivered by this route in recent years. Viral load was slightly, but significantly, higher in those patients who did not receive antiretroviral therapy compared with those that did.

Table 1
Table 1
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Table 2 shows the characteristics of the neonates in both groups. Children exposed to antiretroviral prophylaxis or therapy were born earlier than those who were not exposed, and therefore their birthweight, length and head circumference were lower than in the non-exposed infants. Also, the Apgar score after 5 minutes was higher in the non-exposed group. However, drug withdrawal symptoms were significantly less common in the exposed group, reflecting the fact that fewer of their mothers were injecting drug users. The high frequency of hospitalization in the study group is caused by the prophylaxis regimen. Infants exposed to antiretroviral prophylaxis or therapy had significantly lower levels of haemoglobin, haematocrit, white blood cells and neutrophils.

Table 2
Table 2
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Vertical transmission rate

The evaluation for efficacy was based on the percentage of HIV-infected infants in the control group compared with the group exposed to antiretroviral prophylaxis or therapy. In the non-exposed group, 13 out of 104 neonates were infected with HlV, giving a transmission rate of 12.6% [95% confidence interval (CI) 6.2–19]. In contrast there was no transmission among the 76 infants born after February 1995 and exposed to all or part of the antiretroviral prophylaxis or therapy (95% CI 0–4.7).

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Logistic regression

The results of the logistic regression analyses are shown in Table 3. From the univariate analyses, elective caesarean section results in a borderline significant 70% decrease in risk of transmission (P = 0.075). The Berlin regimen is associated with a significant 90% reduction in HIV transmission [odds ratio (OR) 0.11;P = 0.012] and other therapy with an 80% reduction when compared with no therapy, which has some significance (OR 0.21;P = 0.110). A maternal CD4 cell count of 200–500 × 106 cells/l is associated with a substantial increase in vertical transmission (OR 8.29;P = 0.032) compared with a CD4 cell count > 500 × 106 cells/l, as is a count of < 200 × 106 cells/l (OR 5.40;P = 0.594). The apparent contradiction of the lowest CD4 cell count being associated with a higher risk than the medium CD4 cell count category is explained by the small numbers of infected infants. A unit increase in log10 viral load results in a highly significant sixfold increase in the risk of transmission (OR 6.51; 95% CI 1.96–7.86;P = 0.001). In assessing the effects of adjusting for log10 viral load and CD4 cell count on mode of delivery and therapy, log10 viral load was not found to be an important confounder, and CD4 cell count was found to have only a small impact on the estimates for the OR.

Table 3
Table 3
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Results of multivariate analysis including elective caesarean section, therapy regimen and CD4 cell count category showed that elective caesarean section led to a non-significant 60% reduction in the risk of transmission (OR 0.40; 95% CI 0.09–1.70;P = 0.252) after adjustment for therapy and CD4 cell count. The adjustment reduces the apparent effect of elective caesarean section delivery. Comparing the Berlin regimen with no therapy, risk of transmission is reduced by 85% [OR 0.15; 95% CI 0–0.993;P = 0.049 (borderline significance)]. Other therapy compared with no therapy led to a non-significant reduction of 75% in risk (OR 0.24; 95% CI 0–1.66;P = 0.168). With absolute CD4 cell counts of > 500 × 106 cells/l as the reference group, mothers with a CD4 cell count of 200–500 × 106 cells/l have eight times the risk of transmitting HIV (OR 8.47; 95% CI 1.09–389;P = 0.037) as do mothers with a CD4 cell count < 200 × 106 cells/l, although the increase did not reach statistical significance for the latter group (OR 8.33; 95% CI 0.09–755;P = 0.452). The lack of statistical significance in multivariate analyses is likely to result from the small numbers of infected children in the various categories.

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Adverse effects in neonates
Haematological parameters

There were significant differences in haematological values between the control group and the study group treated with the Berlin regimen (group 1). Haemoglobin concentration, haematocrit, white blood count and neutrophils at birth were decreased in infants in the ZDV group compared with the control group. The differences disappeared within 14–17 days for the white blood cell count and the neutrophils, but lasted for 7 weeks for the haemoglobin and haematocrit (Fig. 1).

Fig. 1
Fig. 1
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Weight, height and growth

The weight and height of both male and female infants born to HIV-infected mothers and exposed to the Berlin regimen of ZDV prophylaxis, none of whom were HIV infected, was markedly lower than the standard values of infants born to uninfected mothers. The difference was especially pronounced at birth, which at least partially reflects the earlier gestational age of the exposed infants, most of whom were delivered by elective caesarean section at 36 weeks. However, weight and height of the exposed children returned to the mean standard values after a few weeks (Fig. 2).

Fig. 2
Fig. 2
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Discussion

The results confirm that it is possible to reduce mother-to-infant transmission of HIV to near zero levels with efficient intervention strategies, including a reduced regimen of ZDV prophylaxis for approximately 2–4 weeks for the mothers and only 10 days for the infants. This short regimen is not only efficient in preventing transmission of HIV from mother to infant it also reduces the (as yet unquantified) risks of ZDV exposure for the children. This efficient Berlin prophylactic ZDV regimen together with a ‘bloodless’ caesarean section [28] prior to the onset of labour is only recommended for women who have no clinical indication for antiretroviral therapy [23–26] and a low risk of obstetrical complications.

The ZDV dosage of 1.3 mg/kg intravenously every 6 h for the neonates corresponds to the established oral dose of 2 mg/kg and is approved for prophylactic use. The rationale for the intravenous route was based on three key points: first, the rapid turnover of plasma virions in HIV-1 infection [29], second, the uncertain resorption of oral medication in enteral nutrition starting immediately after birth and, third, adherence problems in a cohort of partly drug-addicted mothers.

A point of discussion is the timing and method of the elective caesarean section. To have an effect on the rate of vertical transmission, this should be performed prior to the onset of labour and before rupture of membranes [8]. The activation of cytokines and inflammatory substances during labour may allow the passage of HIV carrier cells from decidua through fetal membranes [30]. In our hands, caesarean section was safe and there was no increased risk of perioperative complications [31,32]. However, this procedure was only carried out in non-immunocompromised HlV-infected women in whom the risks of complications would be expected to be similar to those in non-HIV infected women.

A further point of discussion is the role of viral load in mother-to-infant transmission. It has been suggested by others that there may be a threshold level of maternal HIV-1 RNA below which transmission does not occur. However, this is unlikely to be the case as mother-to-infant transmission is a multifactorial event. There is a clear association between viral load and transmission rate independent from other co-factors of transmission [33–37]. The women included in the preventive Berlin regimen had generally low HIV plasma levels and therefore the risk of HIV transmission would be expected to be low, but not non-existent [35].

The risks of infection in antiretroviral-exposed and non-exposed neonates was compared in children who were part of a long-term prospective cohort, although the non-exposed group were historical controls. Therefore the results are limited in terms of scientific evidence by the fact that this was not a placebo-controlled trial. However, not only would the required sample size for such a trial be substantial but also, at the given near-zero transmission rate shown in this study, a placebo control group can no longer be considered to be ethical. Comparison of different ZDV regimens within a clinical trial would require very large sample sizes, given the low rates of vertical transmission achievable in any of the different regimens used.

Concerning the safety of the regimen used in the infants, it is worth noting that the immediate adverse events were comparable to those reported in other studies. In the ACTG 076 trial, anaemia was documented within the first 6 weeks of life. Study results suggest that the low haematocrit of neonates delivered after antenatal ZDV treatment may be a consequence of reduced clonal maturation of erythroid progenitors and the fact that fetal erythroid progenitors are inhibited to a greater extent than maternal progenitors [38]. Our results show that even a greatly reduced intrauterine and postnatal exposure to ZDV has the same effect on the bone marrow system. The depression of the haematopoietic system in the present study up to 2 weeks of age was not associated with a higher incidence of para- and postnatal infections, but long-term effects on the bone marrow tissue cannot be excluded. In contrast to Agostoni et al.[39], there was not a deficit in somatic parameters such as weight or length beyond the age of 8 weeks compared with infants born to HIV-1-seronegative mothers.

Adverse events for women treated with ZDV or for infants in whom ZDV prophylaxis failed to prevent infection are not to be expected. In the ACTG 076 follow-up, no resistance to ZDV developed [40]. In the mothers, there was also no resistance, no rise in viral load and no disease progression after short-term ZDV prophylaxis. Six months postpartum, there were no differences in clinical, immunological or virological disease progression [35]. The report from the Italian Register suggesting a rapid disease progression in HIV-1 perinatally infected children born to mothers receiving ZDV during pregnancy included children born to women who received ZDV monotherapy treatment for clinical indications [41]. Advanced disease in the mother is itself associated with the risk of vertical transmission and rapid disease progression in the first year of life.

We admit that our approach is expensive and requires a neonatal special care unit; therefore, it will be useful in resource-rich settings only. However, we conclude that short-term oral ZDV for the mother in combination with caesarean section before labour and 10 days intravenously ZVD prophylaxis for the infant virtually eliminates HIV transmission to neonates from HlV-infected mothers.

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Acknowledgements

We would like to acknowledge the help we have had from the European Collaborative Study especially from Dr Marie-Louise Newell, Dr Claire Thorne and Mrs Linsay Gray, in critically reviewing the manuscript, for assistance with statistical analysis and for long-term excellent co-operation.

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References

1. Schäfer APA, Friese K. Maßnahmen zur Senkung des maternofetalen HIV-Transmissionsrisikos. Dt Ärztebl 1996, 93: A2234 –A2236.

2. Tovo P-A, de-Martino M, Gabiano C. et al. Mode of delivery and gestational age influcence perinatal HIV-1 transmission. J Acquir Immune Defic Syndr Hum Retrovirol 1996, 11: 88 –94.

3. Maguire A, Sanchez E, Fortuny C, Casabona J, The Working Group on HIV-1 Vertical Transmission in Catalonia. Potential risk factors for vertical HIV1 transmission in Catalonia, Spain: the protective role of Cesarean section. AIDS 1997, 11: 1851 –1857.

4. The European Collaborative Study. Caesarean section and risk of vertical transmission of HIV-1 infection. Lancet 1994, 343: 1464 –1467.

5. Dunn DT, Newell ML, Mayaux MJ. et al. Mode of delivery and vertical transmission of HIV-1: a review of prospective studies. J Acquired Immun Defic Synd 1994, 7: 1064 –1066.

6. Newell ML, Parazzini F, Mandelbrot L. et al. A randomised trial of mode of delivery in women infected with the human immunodeficiency virus. Br J Obstet Gynaecol 1888, 105: 281 –285.

7. The European Mode of Delivery Collaboration. Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial. Lancet 1999, 353: 1035 –1039.

8. The International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus Type 1. N Engl J Med 1999, 340: 977 –987.

9. Connor EM, Sperling RS, Gelber R. et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 1994, 331: 1173 –1180.

10. Mandelbrot L, Le Chenadec J, Berrebi A. et al. Perinatal HIV-1 transmission. :Interaction between zidovudine prophylaxis and mode of delivery in the French Perinatal Cohort. JAMA 1998, 280: 55 –60.

11. Kind Ch, Rudin Ch, Siegrist C. et al. Prevention of vertical HIV transmission: additive protective effect of elective cesarean section and zidovudine prophylaxis. AIDS 1998, 12: 205 –210.

12. Schäfer A, Friese K, Lauper U et al. Influence of cesarean section before parturition and antiretroviral prophylaxis on the materno-fetal transmission of HIV. 12th International World Conference on AIDS. Geneva, June 1998 [poster LB 12466].

13. The European Collaborative Study. Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe. Br J Obstet Gynaecol 1998, 105: 704 –709.

14. Kuhn L, Abrams EJ, Matheson PB. et al. Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. AIDS 1997, 11: 429 –435.

15. Bertolli J, St. Louis ME, Simonds RJ. et al. Estimating the timing of mother-to-child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire. J Infect Dis 1999, 174: 722 –726.

16. Rouzioux C, Costagliola D, Burgard M. et al. Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission by use of a Markov Model. Am J Epidemiol 1995, 142: 1330 –1337.

17. Dunn DT, Brandt CD, Krivine A. et al. The sensitivity of HIV-1 DNA-polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission. AIDS 1995, 9: F7 –F11.

18. Newell ML. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS 1998, 12: 831 –837.

19. Centers for Disease Control. Administration of zIdovudine during late pregnancy and delivery to prevent perinatal HlV-transmission – Thailand, 1996–1998. MMWR 1998, 47: 151 –154.

20. Wiktor SZ, Ekpini E, Karon JM. et al. Short course oral zidovudine for prevention of mother-to-child transmission of HV-1 in Abidjan, Côte d'lvoire: a randomised trial. Lancet 1999, 353: 781 –785.

21. Dabis F, Msellati P, Meda N. et al. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'lvoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. Lancet 1999, 353: 786 –792.

22. Wade NA, Birkhead GS, Warren BL. et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med 1998, 339: 1409 –1414.

23. Centers for Disease control. Report of the NIH Panel to define principles of therapy of HIV infection and guidelines for the use of antiretroviral agents in HlV-infected adults and adolescents. MMWR 1998, 47: 3 –82.

24. Grosch-Wörner I, Schäfer A, Friese K, Brockmeyer N. HlV-Therapie in der Schwangerschaft. Dt Ärztebl 2000, 97: A99 –A103.

25. Tovo PA, Newell ML, Mandelbrot L, Semprini E, Giaquinto C. Recommendations for the management of HlV-infected women and their infants – a European consensus. Prenat Neonat Med 1999, 4: 3 –17.

26. Centers for Disease Control. Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR 1994, 43: 1 –10.

27. Hesse V. Wachstum und Reifung. In:Endokrinologie Grundlagen-Klinik-Praxis. Edited by Meng W, Ziegler R. München: Urban & Schwarzenberg; 1997 (Ch 2): 105 –131.

28. Towers CV, Deveikis A, Asrat T, Major C, Nageotte MP. A ‘bloodless cesarean section’ and perinatal transmission of the human immunodeficiency virus. Am J Obstet Gynecol 1998, 179: 708 –714.

29. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 Iymphocytes in HIV-1 infection. Nature 1995, 373: 123 –126.

30. Rokos K, Wang H, Seeger J, Schafer A, Pauli G. Transport of viruses through fetal membranes: an in vitro model of perinatal transmission. J Med Virol 1998, 54: 313 –319.

31. Ricci F, Parazzini F, Pardi G. The Italian trial on mode of delivery in HlV-positive woman study group: caesarean section and antiretroviral treatment. Lancet 1999, 355: 496. 496.

32. Grubert TA, Prindell D, Kastner R, Lutz-Friedrich R, Belohradsky BH, Dathe O. Complications after caesaren section in HlV-infected women not taking antiretroviral treatment. Lancet 1999, 354: 1612 –1613.

33. Mofenson LM, Lambert JS, Stiehm ER. et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. N Engl J Med 1999, 341: 385 –393.

34. The European Collaborative Study. Maternal viral load and vertical transmission of HIV-1: an important factor but not the only one. AIDS 1999, 13: 1377 –1385.

35. Sperling RS, Shapiro DE, McSherry GD. et al. Safety of the maternal–infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study. AIDS 1998, 12: 1805 –1813.

36. Plaeger S, Bermudez S, Mikyas Y. et al. Decreased CD8 cell-mediated viral suppression and other immunological characteristics of women who transmit human immunodeficiency virus to their infants. J Infect Dis 1999, 179: 1388 –1394.

37. Garcia PM, Kalish LA, Pitt J. et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. N Engl J Med 1999, 341: 394 –402.

38. Shah MM, Li Y, Christensen RD. Effects of perinatal zidovudine on hematopoiesis: a comparison of effects on progenitors from human fetuses versus mothers. AIDS 1996, 10: 1239 –1247.

39. Agostoni C, Zuccotti GV, Giovannini M. et al. Growth in the first two years of uninfected children born to HIV-1 seropositive mothers. Arch Dis Child 1998, 79: 175 –178.

40. McSherry GD, Shapiro DE, Coombs RW. et al. The effects of zidovudine in the subset of infants infected with human immunodeficiency virus type-1 (Pediatric AIDS Clinical Trials Group Protocol 076). J Pediatr 1999, 134: 717 –724.

41. The Italian Register for HIV Infection in Children. Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy. AlDS 1999, 13: 927 –933.

Keywords:

epidemiology; vertical transmission; caesarean section; zidovudine; prophylaxis

© 2000 Lippincott Williams & Wilkins, Inc.

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