38 cases of neonatal group B streptococcal (GBS) sepsis (31 with early onset and 7 with late onse... more 38 cases of neonatal group B streptococcal (GBS) sepsis (31 with early onset and 7 with late onset) were observed during the years 1976-1982. Early onset disease showed the following clinical characteristics: 1. frequent lack of risk factors for infection in obstetric history, 2. very early onset of symptoms of respiratory distress, 3. rapid development of shock after only minor or missing clinical signs of infection, and 4. unspecific findings on chest radiography. Neutropenia or marked leukocyte left shift as well as the presence of gram-positive cocci in gastric or tracheal aspirate proved to be useful diagnostic clues. The latex agglutination test for the detection of GBS-antigen in urine yielded in our hands many false positive results and unspecific reactions. Given the big difficulties of early diagnosis of early onset GBS-sepsis, the relatively liberal use of antibiotics in newborns with respiratory distress is probably unavoidable. Hereby prior culturing of blood and early termination of antibiotic therapy with negative cultures (of blood, CSF, tracheal aspirate) seems essential to us. The clinical significance of newer therapeutic (granulocyte transfusions, exchange transfusions, immunoglobulins) and prophylactic (intra-partum antibiotics, vaccination) modalities is according to the current literature still not clear in many respects.
Cord-blood sera of 36 babies born to HIV-positive mothers in Switzerland were tested for immunogl... more Cord-blood sera of 36 babies born to HIV-positive mothers in Switzerland were tested for immunoglobulin (Ig) M or IgA by HIV Western blot. IgM was found in 28, and IgA in 19 of unabsorbed sera. Preabsorption with immobilized protein A or G was used to remove IgG, which allowed differentiation between HIV-specific and IgG-specific IgM or IgA. Protein G proved superior and showed that 30% of 23 sera had HIV-specific IgM, while 48% had HIV-specific IgA. HIV-specific IgM and/or IgA was found in 13 out of 21 cases (62%); four out of 21 (19%) had both. HIV-specific IgM reacted most frequently with pol or env proteins, while HIV-specific IgA reacted more frequently with gag than pol; no IgA were directed against env proteins. IgG-specific IgM and IgA, mostly at gag bands, were present in 83 and 38%, respectively. Thus, a large percentage of children born to HIV-positive mothers have HIV-specific IgA and/or IgM which can be distinguished from IgG-specific IgA or IgM, which is also present in the majority of such children. Future studies will have to show whether these antibodies are of diagnostic relevance.
A comprehensive cost-benefit analysis of possible screening strategies for congenital toxoplasmos... more A comprehensive cost-benefit analysis of possible screening strategies for congenital toxoplasmosis is necessary as a basis for the decision whether or not screening is efficient and socially desirable. The total costs of the disease in Switzerland were calculated for the year 1990. Direct costs (all diagnostic and therapeutic interventions, including care of handicapped children) and indirect costs (partial and total work losses in the future) were taken into account. Today, the direct costs amount to approx. SFr. 20 mio per year (i.e. approx. SFr. 2.8 mio per million population). The indirect costs were calculated at SFr. 4 mio per year. Moreover, the costs incurred with three possible screening programs (1 test with all pregnant women, with 1, 2 or 5 additional tests, depending on the strategy) were estimated, together with the concomitant cost savings. The financial resources needed for the screenings would amount to SFr. 7 mio-18 mio per year, depending on the strategy chosen. However, the possible savings would be in the range of SFr. 4 mio-12 mio only. The possible savings are, in any case, of the same order of magnitude as the costs for screening. Screening would become cost-efficient if costs for the serological tests could be lowered.
Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study name... more Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study named "HIV and Pregnancy" financed by the Swiss Federal Office of Health (No. 90-7007 and 93-7131). Of a total of 228 recorded pregnancies 154 continued to parturition. Until now it has been definitively established whether or not 89 offsprings have been infected with HIV by their mothers. According to clinical and immunological findings most of the pregnant women are still in early, stable stages of HIV-infection (stages II and III of the CDC classification system in 94% of the subjects; mean CD4-cell count around 600/microliters). HIV infection was the consequence of an intravenous substance abuse in two thirds of the women. Detailed interviews revealed an alarming negligence with regard to compliance with safer sex recommendations and contraception. Advisory services of specialized AIDS information centers have very rarely been called on. In our group, the vertical transmission rate shows a statistically significant correlation with low maternal anti-HIV-p24 antibody titers, high serum neopterin- and IgA-concentrations, and also with the use of forceps and vacuum in vaginal delivery. Maternal substance abuse but not HIV infection itself resulted in an incidence of preterm deliveries roughly twice as high as in the normal Swiss population.
To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV trans... more To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. Prospective study. Obstetric and paediatric clinics in Switzerland. Children of mothers with HIV infection identified before or at delivery. Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. HIV infection status of children. In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.
The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxopla... more The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxoplasmosis; (2) the natural course of fetal infection; (3) the influence of antitoxoplasma therapy on the course of the disease; (4) methods for diagnosing the toxoplasma infection and assessing the severity of the disease; (5) currently used antitoxoplasma drugs and different therapeutic regimens. The second part suggests a practical approach to the problem of congenital toxoplasma infection, including diagnostic work-up, drug therapy, and follow-up. This practical approach is modulated according to the clinical syndrome in the infant and diagnostic and therapeutic considerations in the mother.
Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibito... more Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibitors in children is limited. An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3-16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the current treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed. Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/microl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean ...
In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively fol... more In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively followed up between January 1, 1990, and October 30, 1993. 69.8% were infected by intravenous drug abuse and 91.5% were asymptomatic (CDC classes II and III) in early pregnancy. 48 (21.0%) were first discovered to be HIV-infected during the index pregnancy: 46 of these had risk factors. The present epidemiologic development does not seem to warrant a general HIV-screening in pregnancy at this time. 71 pregnancies (31%) were terminated; 158 children were born, 17 (23.3%) of the 73 definitely classified are HIV-infected. An asymptomatic HIV infection with a sufficiently high (> 200/microliters) CD4 cell count has no proven influence on the pregnancy. Otherwise, however, maternal infectious diseases can lead to prematurity. For mothers with i.v. drug abuse, there is a significantly higher incidence of prematurity and fetal growth retardation. The maternal HIV infection can be transmitted to...
In a national prospective study of risk factors for mother-to- child transmission of human immu- ... more In a national prospective study of risk factors for mother-to- child transmission of human immu- nodeficiency virus (HIV), 316 chil- dren of HIV-positive mothers were followed up for at least 6 months. In- fection status was determined in 254 of them and 46 were found to be in- fected giving a transmission rate of l 8.1%. Univariate analysis of poten-
Lithium medication during pregnancy is uncommon and the problems of a neonate who has been expose... more Lithium medication during pregnancy is uncommon and the problems of a neonate who has been exposed to lithium represents a rare situation in neonatology. The clinical presentation and management of a newborn whose mother received lithium during pregnancy is presented. The newborn manifested a four day course of lethargy with unexplained high lithium levels in the adult toxic range. The infant improved clinically under intravenous hydration therapy, nevertheless lithium serum levels increased again and we did not know for certain if our clinical instinct or the actual figures were correct. Finally we noticed that our confusion had resulted from test tubes containing lithium heparine.
The performance in pediatric human immunodeficiency virus type 1 (HIV-1) infection of a signal-am... more The performance in pediatric human immunodeficiency virus type 1 (HIV-1) infection of a signal-amplification boosted ELISA for HIV-1 p24 antigen in plasma after heat-mediated immune complex dissociation was prospectively compared with polymerase chain reaction-based procedures. Diagnostic sensitivity and specificity of the p24 antigen test were 100% and 99.2%, respectively. Quantification revealed RNA in 85.7% and p24 antigen in 87.4% of 230 samples from 25 infected children. Concentrations of these indices in individual samples correlated (P<.0001). Introduction or modification of antiretroviral treatment showed concordant responses of RNA and p24 antigen in 39 (90.7%) of 43 instances. The treatment-induced changes in concentrations of RNA were higher than those of p24 antigen in 11 instances. In 1 instance, however, the concentration change of p24 antigen was greater than that of RNA (P=. 002). Variation of RNA concentrations was more marked than that of p24 antigen (P=.002). The p24 antigen test was equivalent to PCR for diagnosing and monitoring pediatric HIV-1 infection.
Immune complex formation causes underdetection of p24 antigen in human immunodeficiency virus (HI... more Immune complex formation causes underdetection of p24 antigen in human immunodeficiency virus (HIV) infection. Briefly boiling diluted plasma releases all complexed antigen, which can then be measured by some commercial assays. In a retrospective pediatric cohort study, the specificity of this procedure in 390 uninfected samples was 96.9% after initial testing and 100% after neutralization. Sensitivity among 125 postnatal infected samples was, at a detection of 2 pg/mL, 96.0% (97% neutralizable) compared with 47.7% for regular antigen (76% neutralizable), 96% for polymerase chain reaction, and 77% for viral culture. The high sensitivity and specificity of heat-denatured antigen was confirmed by prospectively testing 113 additional samples. Quantitative analysis of samples from infected infants showed low levels of p24 antigen in 29% of cord blood sera, a postnatal increase to levels that were during the first 6 months of life inversely associated with survival, and persistence of antigenemia thereafter independent of clinical status. Prevalence and antigen levels were significantly lower in mothers. The persistent antigenemia in children indicates that their immune systems cannot restrict HIV expression as efficiently as those of adults.
In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds ... more In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds reduction of perinatal human immunodeficiency virus (HIV) type 1 transmission with zidovudine chemoprophylaxis. However, zidovudine alone does not fully suppress HIV replication, and chemoprophylaxis with zidovudine alone might select for zidovudine-resistant viral variants, decreasing the efficacy of zidovudine prophylaxis and affecting future responses to combined antiretroviral regimens. Sixty-two HIV-infected pregnant women consecutively enrolled in the ongoing Swiss HIV and Pregnancy Study were prospectively evaluated for the presence or development of zidovudine resistance by analysis of codon 215 of the reverse transcriptase gene. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. Postnatal evaluation was completed in all children of mothers harboring the mutation. None was HIV-infected. The observed prevalence of codon 215 mutations of 9.6% raises important concerns regarding the future use of the PACTG 076 regimen.
38 cases of neonatal group B streptococcal (GBS) sepsis (31 with early onset and 7 with late onse... more 38 cases of neonatal group B streptococcal (GBS) sepsis (31 with early onset and 7 with late onset) were observed during the years 1976-1982. Early onset disease showed the following clinical characteristics: 1. frequent lack of risk factors for infection in obstetric history, 2. very early onset of symptoms of respiratory distress, 3. rapid development of shock after only minor or missing clinical signs of infection, and 4. unspecific findings on chest radiography. Neutropenia or marked leukocyte left shift as well as the presence of gram-positive cocci in gastric or tracheal aspirate proved to be useful diagnostic clues. The latex agglutination test for the detection of GBS-antigen in urine yielded in our hands many false positive results and unspecific reactions. Given the big difficulties of early diagnosis of early onset GBS-sepsis, the relatively liberal use of antibiotics in newborns with respiratory distress is probably unavoidable. Hereby prior culturing of blood and early termination of antibiotic therapy with negative cultures (of blood, CSF, tracheal aspirate) seems essential to us. The clinical significance of newer therapeutic (granulocyte transfusions, exchange transfusions, immunoglobulins) and prophylactic (intra-partum antibiotics, vaccination) modalities is according to the current literature still not clear in many respects.
Cord-blood sera of 36 babies born to HIV-positive mothers in Switzerland were tested for immunogl... more Cord-blood sera of 36 babies born to HIV-positive mothers in Switzerland were tested for immunoglobulin (Ig) M or IgA by HIV Western blot. IgM was found in 28, and IgA in 19 of unabsorbed sera. Preabsorption with immobilized protein A or G was used to remove IgG, which allowed differentiation between HIV-specific and IgG-specific IgM or IgA. Protein G proved superior and showed that 30% of 23 sera had HIV-specific IgM, while 48% had HIV-specific IgA. HIV-specific IgM and/or IgA was found in 13 out of 21 cases (62%); four out of 21 (19%) had both. HIV-specific IgM reacted most frequently with pol or env proteins, while HIV-specific IgA reacted more frequently with gag than pol; no IgA were directed against env proteins. IgG-specific IgM and IgA, mostly at gag bands, were present in 83 and 38%, respectively. Thus, a large percentage of children born to HIV-positive mothers have HIV-specific IgA and/or IgM which can be distinguished from IgG-specific IgA or IgM, which is also present in the majority of such children. Future studies will have to show whether these antibodies are of diagnostic relevance.
A comprehensive cost-benefit analysis of possible screening strategies for congenital toxoplasmos... more A comprehensive cost-benefit analysis of possible screening strategies for congenital toxoplasmosis is necessary as a basis for the decision whether or not screening is efficient and socially desirable. The total costs of the disease in Switzerland were calculated for the year 1990. Direct costs (all diagnostic and therapeutic interventions, including care of handicapped children) and indirect costs (partial and total work losses in the future) were taken into account. Today, the direct costs amount to approx. SFr. 20 mio per year (i.e. approx. SFr. 2.8 mio per million population). The indirect costs were calculated at SFr. 4 mio per year. Moreover, the costs incurred with three possible screening programs (1 test with all pregnant women, with 1, 2 or 5 additional tests, depending on the strategy) were estimated, together with the concomitant cost savings. The financial resources needed for the screenings would amount to SFr. 7 mio-18 mio per year, depending on the strategy chosen. However, the possible savings would be in the range of SFr. 4 mio-12 mio only. The possible savings are, in any case, of the same order of magnitude as the costs for screening. Screening would become cost-efficient if costs for the serological tests could be lowered.
Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study name... more Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study named "HIV and Pregnancy" financed by the Swiss Federal Office of Health (No. 90-7007 and 93-7131). Of a total of 228 recorded pregnancies 154 continued to parturition. Until now it has been definitively established whether or not 89 offsprings have been infected with HIV by their mothers. According to clinical and immunological findings most of the pregnant women are still in early, stable stages of HIV-infection (stages II and III of the CDC classification system in 94% of the subjects; mean CD4-cell count around 600/microliters). HIV infection was the consequence of an intravenous substance abuse in two thirds of the women. Detailed interviews revealed an alarming negligence with regard to compliance with safer sex recommendations and contraception. Advisory services of specialized AIDS information centers have very rarely been called on. In our group, the vertical transmission rate shows a statistically significant correlation with low maternal anti-HIV-p24 antibody titers, high serum neopterin- and IgA-concentrations, and also with the use of forceps and vacuum in vaginal delivery. Maternal substance abuse but not HIV infection itself resulted in an incidence of preterm deliveries roughly twice as high as in the normal Swiss population.
To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV trans... more To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. Prospective study. Obstetric and paediatric clinics in Switzerland. Children of mothers with HIV infection identified before or at delivery. Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. HIV infection status of children. In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.
The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxopla... more The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxoplasmosis; (2) the natural course of fetal infection; (3) the influence of antitoxoplasma therapy on the course of the disease; (4) methods for diagnosing the toxoplasma infection and assessing the severity of the disease; (5) currently used antitoxoplasma drugs and different therapeutic regimens. The second part suggests a practical approach to the problem of congenital toxoplasma infection, including diagnostic work-up, drug therapy, and follow-up. This practical approach is modulated according to the clinical syndrome in the infant and diagnostic and therapeutic considerations in the mother.
Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibito... more Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibitors in children is limited. An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3-16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the current treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed. Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/microl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean ...
In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively fol... more In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively followed up between January 1, 1990, and October 30, 1993. 69.8% were infected by intravenous drug abuse and 91.5% were asymptomatic (CDC classes II and III) in early pregnancy. 48 (21.0%) were first discovered to be HIV-infected during the index pregnancy: 46 of these had risk factors. The present epidemiologic development does not seem to warrant a general HIV-screening in pregnancy at this time. 71 pregnancies (31%) were terminated; 158 children were born, 17 (23.3%) of the 73 definitely classified are HIV-infected. An asymptomatic HIV infection with a sufficiently high (> 200/microliters) CD4 cell count has no proven influence on the pregnancy. Otherwise, however, maternal infectious diseases can lead to prematurity. For mothers with i.v. drug abuse, there is a significantly higher incidence of prematurity and fetal growth retardation. The maternal HIV infection can be transmitted to...
In a national prospective study of risk factors for mother-to- child transmission of human immu- ... more In a national prospective study of risk factors for mother-to- child transmission of human immu- nodeficiency virus (HIV), 316 chil- dren of HIV-positive mothers were followed up for at least 6 months. In- fection status was determined in 254 of them and 46 were found to be in- fected giving a transmission rate of l 8.1%. Univariate analysis of poten-
Lithium medication during pregnancy is uncommon and the problems of a neonate who has been expose... more Lithium medication during pregnancy is uncommon and the problems of a neonate who has been exposed to lithium represents a rare situation in neonatology. The clinical presentation and management of a newborn whose mother received lithium during pregnancy is presented. The newborn manifested a four day course of lethargy with unexplained high lithium levels in the adult toxic range. The infant improved clinically under intravenous hydration therapy, nevertheless lithium serum levels increased again and we did not know for certain if our clinical instinct or the actual figures were correct. Finally we noticed that our confusion had resulted from test tubes containing lithium heparine.
The performance in pediatric human immunodeficiency virus type 1 (HIV-1) infection of a signal-am... more The performance in pediatric human immunodeficiency virus type 1 (HIV-1) infection of a signal-amplification boosted ELISA for HIV-1 p24 antigen in plasma after heat-mediated immune complex dissociation was prospectively compared with polymerase chain reaction-based procedures. Diagnostic sensitivity and specificity of the p24 antigen test were 100% and 99.2%, respectively. Quantification revealed RNA in 85.7% and p24 antigen in 87.4% of 230 samples from 25 infected children. Concentrations of these indices in individual samples correlated (P<.0001). Introduction or modification of antiretroviral treatment showed concordant responses of RNA and p24 antigen in 39 (90.7%) of 43 instances. The treatment-induced changes in concentrations of RNA were higher than those of p24 antigen in 11 instances. In 1 instance, however, the concentration change of p24 antigen was greater than that of RNA (P=. 002). Variation of RNA concentrations was more marked than that of p24 antigen (P=.002). The p24 antigen test was equivalent to PCR for diagnosing and monitoring pediatric HIV-1 infection.
Immune complex formation causes underdetection of p24 antigen in human immunodeficiency virus (HI... more Immune complex formation causes underdetection of p24 antigen in human immunodeficiency virus (HIV) infection. Briefly boiling diluted plasma releases all complexed antigen, which can then be measured by some commercial assays. In a retrospective pediatric cohort study, the specificity of this procedure in 390 uninfected samples was 96.9% after initial testing and 100% after neutralization. Sensitivity among 125 postnatal infected samples was, at a detection of 2 pg/mL, 96.0% (97% neutralizable) compared with 47.7% for regular antigen (76% neutralizable), 96% for polymerase chain reaction, and 77% for viral culture. The high sensitivity and specificity of heat-denatured antigen was confirmed by prospectively testing 113 additional samples. Quantitative analysis of samples from infected infants showed low levels of p24 antigen in 29% of cord blood sera, a postnatal increase to levels that were during the first 6 months of life inversely associated with survival, and persistence of antigenemia thereafter independent of clinical status. Prevalence and antigen levels were significantly lower in mothers. The persistent antigenemia in children indicates that their immune systems cannot restrict HIV expression as efficiently as those of adults.
In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds ... more In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds reduction of perinatal human immunodeficiency virus (HIV) type 1 transmission with zidovudine chemoprophylaxis. However, zidovudine alone does not fully suppress HIV replication, and chemoprophylaxis with zidovudine alone might select for zidovudine-resistant viral variants, decreasing the efficacy of zidovudine prophylaxis and affecting future responses to combined antiretroviral regimens. Sixty-two HIV-infected pregnant women consecutively enrolled in the ongoing Swiss HIV and Pregnancy Study were prospectively evaluated for the presence or development of zidovudine resistance by analysis of codon 215 of the reverse transcriptase gene. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. Postnatal evaluation was completed in all children of mothers harboring the mutation. None was HIV-infected. The observed prevalence of codon 215 mutations of 9.6% raises important concerns regarding the future use of the PACTG 076 regimen.
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