Clinical and immunologic characteristics and therapeutic interventions in children born to human immunodeficiency virus-infected mothers in southern Taiwan.

Since the late 1990s, the epidemic of human immunodeficiency virus (HIV) infection in Taiwan has expanded dramatically. Pediatric HIV infection has also increased at an alarming pace. Nearly 40% of the HIV-infected children (<10 years) contracted infection through mother-to-child transmission (MTCT). The aims of this study were to evaluate the effects of interventions to prevent MTCT of HIV infection, and to describe the clinical and immunologic characteristics of children born to HIV-seropositive mothers in southern Taiwan. From 1995 to 2003, an observational, longitudinal study of 8 children born to HIV-infected mothers was carried out at a tertiary care university hospital. The median age at enrollment was 0.4 years (range, 1 day-7.5 years), and the mean duration of follow-up was 2.7 years. Four mothers were immigrants from southeastern Asia. Due to antenatal diagnosis of maternal HIV infection, 3 children underwent interventions, including cesarean section, prophylactic use of zidovudine, and bottle-feeding in order to prevent vertical transmission. Five children were born without interventions because of delayed diagnosis of maternal HIV infection. During follow-up, 2 children were found to be HIV-infected and 6 were not infected. The rate of MTCT was lower among patients with interventions (0% vs 40%). In HIV-exposed/non-infected children, the clinical and immunologic assessments were normal during follow-up. Both HIV-infected children progressed to the stage of acquired immunodeficiency syndrome. Early identification of HIV-seropositive pregnant women, implementations to reduce vertical transmission, and introduction of antiretroviral therapy permit optimism in the prevention and treatment of pediatric HIV infection.     

Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers

Although children born to HIV-infected (HIV+) women receiving antiretroviral therapy during pregnancy show virtually no adverse clinical effects at birth, the antiretroviral nucleoside analog drugs are known to damage nuclear and mitochondrial DNA. In this study, biomarkers of mitochondrial toxicity and genotoxicity have been examined in a well-characterized sample set consisting of infants born to HIV-uninfected (HIV-) mothers (n = 30), and HIV- infants (n = 20) born to HIV-infected (HIV+) mothers who received either no antiretroviral therapy (n = 10) or zidovudine (3'-azido-3'-deoxythymidine [AZT]) during pregnancy (n = 10). DNA from cord blood leukocytes and peripheral blood leukocytes taken at 1 and 2 years of age was examined for loss of mitochondrial DNA (mtDNA) and telomere integrity. Telomere length, a measure of nuclear DNA damage, was the same in all infants at birth and at age 1 year. The quantity of mtDNA was assessed relative to nuclear DNA using a polymerase chain reaction-based chemiluminescence detection (PCR-CID) method that determined mitochondrial D Loop gene copies relative to nuclear 18S RNA gene copies by comparison with a standard curve. MtDNA quantity was expressed as a ratio of gene copy numbers. In infants of uninfected mothers (AZT-/HIV-) at the three time points, the ratios were 442 to 515, whereas in infants of untreated AZT-/HIV+ mothers the ratios were 261 to 297, and in infants of AZT-treated (AZT+/HIV+) mothers the ratios were 146 to 203. At all three time points, differences between the AZT-/HIV- group and the two HIV+ groups were statistically significant (p <.05), and differences between the AZT-/HIV+ and AZT+/HIV+ groups were also statistically significant (p <.05), demonstrating that AZT exposure causes a persistent depletion of mtDNA. The study shows that children of HIV+ mothers are at risk for mitochondrial damage that is further increased in infants of mothers receiving AZT during pregnancy.     

Epidemiologic modeling to evaluate prevention of mother-infant HIV transmission in Ontario

OBJECTIVES: To evaluate the impact of the Ontario HIV screening program to reduce mother-infant HIV transmission, this study estimated the proportion of preventable transmissions that were prevented. METHODS: Using an iterative spreadsheet model, incidences of HIV infection, AIDS, and AIDS mortality in Ontario women were estimated by exposure category. The number of HIV-infected infants born to HIV-infected mothers was then estimated from conception and abortion rates of HIV-infected women of childbearing age and surveillance data. Finally, the proportion of HIV-infected mothers who received antiretroviral prophylaxis (ARP) was assessed. RESULTS: HIV prevalence in 2001 among women of childbearing age was 1.05 per 1000. From 1984-2001, 764 infants were born to HIV-infected mothers and 180 were infected. From mid-1994-2001, 214 (39%) of the estimated 544 HIV-infected mothers were diagnosed; almost all received ARP. Of 118 preventable infections among infants born in this period, 39 (33%) were prevented. In 2001, only 46% of preventable infections were prevented and 11 preventable transmissions occurred. CONCLUSIONS: HIV prevalence among women in Ontario increased >4-fold from 1990 to 2001. Fewer than half of HIV-infected mothers received ARP and preventable HIV infections continue to occur. Measures to further increase uptake of prenatal HIV screening must be instituted.     

Contribution of bacterial sepsis to morbidity in infants born to HIV-infected Haitian mothers

BACKGROUND: Haiti is a country with a heavy burden of HIV infection in childbearing women. Previous studies have shown that early infant deaths are common in children of HIV-infected women. This study was designed to define the rates of and risk factors for systemic bacterial and mycobacterial infection in such children and to identify the causative agents. METHODS: A cohort of 120 children born to HIV-infected mothers between May 2001 and December 2003 were prospectively observed to 15 months of age. They received comprehensive pediatric care at the GHESKIO Centers. Children were assigned to being HIV-infected by serology, RNA detection, and/or defining clinical illnesses. Blood cultures were obtained before giving antibiotics in children who were febrile or chronically ill. Blood cultures also were obtained at selected visits on well children. RESULTS: The mortality rate in the first 15 months was high, 22 of 106 (207/1,000 live births) in these children. Sixteen (70%) deaths were within 6 months of birth. Fourty-eight blood cultures had clinically significant organisms of which 38 were Staphylococcus aureus. Blood cultures were more likely to be positive in symptomatic and in HIV-infected children. CONCLUSIONS: Despite perinatal HIV treatment, mortality in children born to HIV-infected mothers remained high. Bacteremia, particularly with Staphylococcus aureus, is a partial explanation for excess illness.     

Plasmodium Falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children

BACKGROUND. It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease. METHODS. We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1-seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine. RESULTS. A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those with the acquired immunodeficiency syndrome (AIDS), those who were HIV-1-seropositive throughout the study, those who were born to HIV-1-seropositive mothers but reverted to seronegative, and those who were seronegative throughout the study. During the 13-month period the incidence of malaria in the 36 children with HIV infection in whom AIDS developed was lower, although not significantly so, than in the 37 in whom AIDS did not. CONCLUSIONS. In this study malaria was not more frequent or more severe in children with progressive HIV-1 infection and malaria did not appear to accelerate the rate of progression of HIV-1 disease.     

Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda

OBJECTIVE: To estimate 2-year mortality rates in HIV-1-infected and uninfected infants born to HIV and HIV mothers. METHODS: Data are from a prospective study in rural Rakai District, Uganda. Infant HIV status (determined by polymerase chain reaction) was evaluated at 1 to 6 weeks postpartum and during breast-feeding, and maternal HIV viral load and CD4 levels were measured at the postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess survival of infants by maternal and infant HIV status and by quartiles of viral load. Log-rank tests were used to test the equality of survival functions. RESULTS: Of the 4604 pregnant women, 16.9% were HIV, and the proportion of children infected was 20.9%. Median survival of HIV-infected infants was 23 months. Two-year child mortality rates were 128 of 1000 children born to HIV mothers, 165.5 of 1000 uninfected children born to HIV mothers, and 540.1 of 1000 HIV-infected children (P < 0.0001). Compared with children of HIV mothers, the hazard of child mortality was 2.04 (P < 0.001) if the mother was HIV and 3.78 (P < 0.001) if the infant was also infected. In the adjusted model, the highest quartiles of log10 HIV viral load in infants and mothers were associated with significantly increased hazard of child mortality (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts <200 cells/mL were also significant predictors of child mortality (HR = 2.61). A total of 67.6% of HIV-infected children with viral loads above the median died by the age of 2 years and are in need of early antiretroviral therapy (ART). CONCLUSIONS: More than half of HIV-infected infants died at less than 2 years of age. Therefore, ART may need to be initiated earlier in HIV-infected African children.     

Early detection of HIV-1 in infants by PCR

Infants of HIV-infected mothers are at great risk of becoming infected with HIV during childbirth. Many infants acquire HIV during labor and delivery. Others can acquire HIV through the mixing of fetal and maternal blood as the placenta separates. The duration of membrane rupture, acute chorioamnionitis and invasive delivery techniques that increase the baby's contact with the mother's blood have been associated with higher risks of MTCT during labor and delivery. HIV is present in breast milk and risk of its transmission during breastfeeding depends on several factors, including: infant age, pattern of breastfeeding, breastfeeding duration, breast health, maternal viral load and maternal immune status. Infants born to HIV infected mothers carry their mother's antibodies in their blood into the second year of life, even if the infants themselves are not infected. For this reason, standard HIV antibody tests cannot reliably confirm HIV infection in infants until after the maternal antibodies have disappeared. Tests that can diagnose pediatric HIV infection accurately during the first year of life include HIV-PCR, CD4/CD8 counts, P24 antigen tests, and viral cultures. PCR offers an effective tool to reliably diagnose HIV in a pediatric age group. Nineteen infants born by normal delivery to HIV-1 seropositive mothers were studied by PCR for the HIV1 env gene. Thirteen babies (68.5%) were negative whereas 6 babies were found to be positive (31.5%). Although PCR is one of the most useful tests for this clinical situation, it is not definitive. Therefore, PCR should be interpreted with caution and repeated at regular defined intervals, preferably lasting until the HIV antibody status of the infant is resolved.     

Repeated polymerase chain reaction complementary to other conventional methods for early detection of HIV infection in infants born to HIV-infected mothers

The efficacy of a polymerase chain reaction (PCR) method for early detection of human immunodeficiency virus (HIV) in infants at risk for HIV infection was assessed. The PCR method was added to the routine laboratory test programme in these patients in 1988. PCR was performed in a total of 26 children at risk (age range 2 days to 58 months), including 17 infants born to HIV-infected mothers, who were followed up clinically from the time of birth for a mean period of 23 months (range 6 to 54) in a prospective study. Twelve children were PCR-positive. Eight had AIDS, ARC or symptoms suggestive of HIV infection. All these patients had at least one culture positive for HIV (6/8) and/or one positive serum p24-antigen test (5/8). One child was repeatedly PCR positive, but asymptomatic as well as virus- and antigennegative. Three asymptomatic children with a single positive PCR result were PCR negative in subsequent tests. Fourteen children with negative PCR did not show clinical or immunological signs suggestive of HIV infection. Their cultures for HIV and antigen-p24 assays were negative. It is concluded that in addition to clinical and immunological parameters PCR is a useful technique for diagnosis of HIV infection in infants born to HIV-infected mothers. However, in case of negative HIV cultures and/or serum p24-antigen tests, single positive PCR results in asymptomatic patients must be interpreted with caution and should be confirmed by repeated tests.     

Natural pregnancies in HIV-serodiscordant couples receiving successful antiretroviral therapy

Increasing numbers of HIV-serodiscordant heterosexual couples are concerned about the chances for pregnancy. We reviewed all natural pregnancies attained by HIV-serodiscordant couples seen in 3 clinics in Spain, in which the infected partner had undetectable plasma viremia while receiving highly active antiretroviral therapy (HAART). In the case of HIV-infected mothers, only those with undetectable viremia during pregnancy and at delivery were chosen. A total of 62 HIV-serodiscordant couples, 22 HIV-infected women (mean CD4 count of 522 cells/microL, 55% hepatitis C virus [HCV]-seropositive) and 40 HIV-infected men (mean CD4 count of 629 cells/microL, 75% HCV-seropositive), were recorded. Overall, 76 natural pregnancies occurred, and 68 children were born. There were 9 fetal deaths, 1 twin pregnancy, 6 couples with 2 consecutive babies, and 4 couples with 3 consecutive newborns. There were no cases of HIV seroconversion in uninfected sexual partners. One case of vertical HIV transmission occurred, however. Serodiscordant couples attaining natural pregnancy are exposed to a negligible risk of sexual transmission of HIV when the infected partner presents with complete suppression of plasma viremia while receiving HAART.     

Pediatric human immunodeficiency virus infection.

In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies.     

Hepatitis B virus seroprevalence among HIV-infected patients receiving combination antiretroviral therapy three decades after universal neonatal hepatitis B immunization program in Taiwan

Background/purposeThis multicenter study aimed to evaluate the seroprevalence of hepatitis B virus (HBV) and the use of combination antiretroviral therapy (cART) among patients receiving HIV care in Taiwan.MethodsWe retrospectively reviewed the medical records of HIV-infected adult patients who initiated cART at 11 designated hospitals in Taiwan between 2012 and 2016. The clinical information collected included serological profiles on HBV, hepatitis C virus (HCV), and syphilis, plasma HIV RNA load, nadir CD4 cell count, and antiretrovirals with activity against both HBV and HIV (tenofovir disoproxil fumarate [TDF], lamivudine [LAM], and emtricitabine [FTC]).ResultsWe analyzed 1800 HIV-infected patients; 1742 (96.8%) were male and 794 (44.1%) were born after July, 1986, when nationwide universal neonatal HBV vaccination was implemented. HBsAg positive results were 11.6% (209/1800), which decreased significantly from 18.1% (182/1006) in those born before July 1986 to 3.4% (27/794) in those born after. In multivariable analysis, HBsAg positivity was significantly associated with age (adjusted odds ratio [aOR] 1.06, 95% confidence interval [CI] 1.05–1.08), CD4≧200 cells/μL (aOR 0.73, 95% CI 0.53–0.99), and HCV seropositivity (aOR 1.62, 95% CI 1.06–2.50). Of 209 HBV/HIV-coinfected patients, 31.1% started cART containing only LAM with anti-HBV activity, while 68.9% started cART containing TDF plus LAM or coformulated TDF/FTC.ConclusionsThe overall prevalence of HBV/HIV coinfection remained high among HIV-infected patients in Taiwan. Despite recommendations of the HIV treatment guidelines for the management of HBV infection, a substantial proportion of HIV/HBV-coinfected patients received cART containing only LAM for HBV infection.     

HIV暴露婴儿HBV感染状况研究

目的 调查HIV阳性母亲所生婴儿(HIV暴露婴儿)的HBV感染状况,间接评估该人群HBV疫苗免疫效果.方法 从我国HIV阳性母亲所生婴儿干血斑样本库中随机抽取106份HIV感染婴儿样本(HIV阳性组)、107份HIV未感染婴儿样本(HIV阴性组),采集100份HIV阴性母亲所生婴儿的全血制备成干血斑样本(HIV未暴露组).所有样本用Qiagen试剂盒进行HBV DNA检测.用Fisher精确概率法比较样本组间HBV感染率差异;HIV暴露组和我国1～4岁儿童HBV感染率的比较通过直接计算Poisson分布的累计概率进行假设检验.结果 HIV阳性组中HBV感染率是2.83％,阴性组和未暴露组中均未检测到HBV感染,三组间感染率差异无统计学意义.HIV暴露婴儿校正后HBV感染率为0.18％,不高于我国l～4岁儿童HBV感染率0.32％.结论 我国HIV暴露婴儿HBV感染率较低,HBV免疫策略实施效果良好,未受到HIV暴露的影响.     

When HIV is kid stuff

Most children with HIV contracted the virus from their infected mothers. HIV transmission rates have dropped to 10 percent with the advent of aggressive AZT treatment during pregnancy and further treatment of the infant for six weeks after birth, and the importance of preventing transmission cannot be overstated. However, AZT treatment can lead to resistance, and some children are born infected with drug-resistant strains of the virus. Children of HIV-infected mothers always test positive at birth but may seroconvert by eighteen months. HIV treatments for pediatric patients are complicated by the children's own immature immune systems, general intolerance to treatment, and their parents' inability to cope with the complex nature of the disease. A typical treatment regimen for a young patient and her mother is included to demonstrate how rigorous the treatment schedules are.     

Isolation of Lautropia mirabilis from Oral Cavities of Human Immunodeficiency Virus-Infected Children

Lautropia mirabilis, a pleomorphic, motile, gram-negative coccus, has been isolated from the oral cavities of 32 of 60 (53.3%) children infected with human immunodeficiency virus (HIV) and 3 of 25 (12.0%) HIV-uninfected controls; the association of L. mirabilis isolation with HIV infection is significant (P < 0.001). All children in the study, both HIV-infected children and controls, were born to HIV-infected mothers. The presence of this bacterium was not associated with clinical disease in these children. The HIV-infected children with L. mirabilis did not differ from the HIV-infected children without L. mirabilis in immunological status, clinical status, or systemic medications. The role of HIV infection itself or concomitant factors in the establishment of L. mirabilis in the oral cavity remains to be elucidated.     

Prospective study of mother-to-infant transmission of hepatitis C virus (HCV) infection

Seventy-five women with anti-hepatitis C virus (HCV) antibody were enrolled prospectively during pregnancy or at delivery for study of mother-to-child transmission of HCV. Twenty-three women were coinfected with the human immunodeficiency virus (HIV). Seventy babies were monitored for at least 6 months. HCV infection was diagnosed in six infants (8.6%), four of whom were born to anti-HIV–positive mothers. HCV RNA was first detected between 2 and 6 months, and the genotypes of infected babies matched those of their mothers (type 1: n = 4; type 3: n = 2). Identical master sequences of the hypervariable region (HVR1) were detected in a mother–infant pair. In three babies coinfected with HCV and HIV, anti-HCV disappeared between 2 and 7 months, being persistently negative in two cases monitored for 11 and 26 months. Transmitting mothers did not differ significantly from those who did not transmit the infection with anti-HIV, HCV genotypes, and viral load at delivery, but had lower rate of reactivity to C100 by the recombinant immunoblot assay (RIBA) (P < .01). This prospective study confirms transmission of HCV from anti-HIV–negative mothers (4.4% in this series). Absence of anti-C100 antibodies at delivery is apparently related to increased risk of vertical transmission. Seronegative HCV infection can be observed in children coinfected with HIV. J. Med. Virol. 54:12–19, 1998. © 1998 Wiley-Liss, Inc.     

Perinatally cotransmitted human herpesvirus 6 is activated in children born with human immunodeficiency virus infection

OBJECTIVE: To evaluate the mother-to-child transmission profile of human immunodeficiency virus (HIV) as well as human herpesvirus 6 (HHV-6) and to examine active replication of HHV-6 in the HIV-infected mothers and their newborns. STUDY DESIGN/METHODS: This polymerase chain reaction (PCR)-based detection was done using DNA from peripheral blood mononuclear cells (PBMCs) and milk cells from the mothers, PBMC from the newborns, and DNA derived from plasma and cell-free milk fluid from mothers and plasma of the newborns. None of the mothers received antiretroviral treatment. RESULTS: HIV was transmitted to 50% newborns and, of 36 total mothers, 8 had actively replicating HHV-6 detectable in their plasma and 2 also had it in the lactosera. Among the neonates. HHV-6 was found in the PBMC DNA of seven and in the plasma fractions of five, the latter five newborns were all HIV-infected at birth. CONCLUSION: Perinatally cotransmitted HHV-6 was always activated in the neonates who were born with HIV infection. Also, HHV-6 can be detected in the milk cells and the activated virus may be present in the lactosera of some of these HlV-infected mothers.     

Clinical presentation and course of acute hepatitis C infection in HIV-infected patients

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.     

Prevention and treatment of VZV infections in patients with HIV

Varicella zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected patients are known to have a different disease spectrum from that seen in other types of patients. Varicella in children with HIV infection is likely to be more serious than in otherwise healthy children and routine antiviral therapy is recommended. There is evidence that the development of varicella in HIV-infected children is not associated with progression to AIDS, suggesting that it may be safe to immunize HIV-infected children with live attenuated varicella vaccine. There are no published data on varicella in HIV-infected adults, however, probably because most adults have already experienced varicella prior to HIV infection. Zoster in HIV-infected children differs somewhat from that in HIV-infected adults. In particular, HIV-infected children who develop varicella in the setting of severe immunodeficiency are at an especially high risk to develop zoster. Given the low rate of toxicity of aciclovir as well as its ease of administration and its efficacy in hastening the healing of VZV infections, prompt treatment with this antiviral agent is recommended for both HIV-infected children and adults. Foscarnet should be used for zoster that is strongly suspected or proven to be caused by aciclovir-resistant VZV. Patients with HIV for whom there is no evidence of significant immunosuppression and who have not had varicella should be immunized with live attenuated varicella vaccine as a preventative measure for both varicella and zoster. It is hoped that immunization of VZV seropositive HIV-infected patients will decrease the incidence of zoster. Studies to determine this are under way.     

Broad Spectrum of Time of Detection, Primary Symptoms and Disease Progression in Infants with HIV-1 Infection

 The relationship between time of HIV-1 detection, appearance of symptoms and disease progression was studied in all 24 HIV-1-infected infants from a cohort of 117 children who were born to HIV-1-infected mothers and monitored from birth. HIV isolation from plasma and mononuclear cells, HIV-1 DNA PCR (polymerase chain reaction) and, retrospectively, a quantitative assay for HIV-1 RNA were used for virus detection. Two infants possibly exhibited a symptomatic primary HIV infection. More children with than without symptoms during the first year of life progressed to immunological class 3 (P=0.013) and to AIDS or death (P=0.003) during follow-up. HIV-1 was detected within 4 days of age in 4 of 16 infants: 3 of them became symptomatic within 1 year, as did 6 of the remaining 12 infants (not statistically significant). All four infants in whom virus was detected within 4 days of age progressed to severe immunosuppression, compared to 6 of 14 in whom the virus detection test was initially negative prior to the first positive result (n.s.). Two children with previous repeatedly negative HIV detection tests were diagnosed with HIV-1 infection at 8 and 9 months, respectively. Repeated blood sampling is needed for the diagnosis of HIV-1 infection in perinatally exposed infants, and virus detection tests for exclusion of HIV-1 infection must be used with caution.