ABSTRACT
OBJECTIVE: To determine whether vitamin A deficiency is associated with maternal-infant HIV transmission among HIV-infected pregnant women in two United States cities. METHODS: Third trimester serum vitamin A levels were evaluated using high-performance liquid chromatography in 133 HIV-infected women who delivered livebirths during May 1986 to May 1994 and whose infants had known HIV infection status. RESULTS: Sixteen per cent (seven out of 44) of the transmitting mothers and 6% (five out of 89) of the non-transmitting mothers had severe vitamin A deficiency (< 0.70 mumol/l; P = 0.05). Maternal-infant transmission was also associated with prematurity < 37 weeks gestation (P = 0.02), and Cesarean section delivery (P = 0.04), CD4 percentage (P = 0.03) and marginally associated with duration of membrane rupture of > or = 4 h (P = 0.06) by univariate analysis. In a multivariate logistic regression model, severe vitamin A deficiency [adjusted odds ratio (AOR), 5.05; 95% confidence interval (CI), 1.20-21.24], Cesarean section delivery (AOR, 3.75; 95% CI, 1.10-12.87), and prematurity (AOR, 2.25; 95% CI, 1.22-4.13) were associated with transmission after adjusting for CD4+ percentage, and duration of membrane rupture. CONCLUSION: Increased risk of maternal-infant transmission was associated with severe vitamin A deficiency among non-breastfeeding women in these cohorts from the United States.
Subject(s)
HIV Infections/transmission , HIV-1 , Infectious Disease Transmission, Vertical , Vitamin A Deficiency/complications , Adult , Breast Feeding , Female , Gestational Age , Humans , Maternal-Fetal Exchange , Pregnancy , Pregnancy Trimester, Third , Prospective Studies , Vitamin A/bloodABSTRACT
BACKGROUND: Clinical trials in adults have demonstrated the efficacy of highly active antiretroviral therapy (HAART) to suppress replication of HIV-1 to nondetectable levels, but lower success rates have been observed in practice. We sought to determine the efficacy of HAART in our population of HIV-1-infected children and to identify determinants of efficacy, especially the role of adherence to prescribed antiretrovirals. METHODS: The viral load and CD4+ T cell responses of 72 children with perinatally acquired HIV-1 treated with HAART including a protease inhibitor for at least 90 days were examined retrospectively in relation to adherence, as measured by pharmacy records for the first 180 days of HAART. RESULTS: Patients were defined as adherent if > or =75% of protease inhibitors and > or =75% of all antiretroviral prescriptions were filled. Of the 42 patients (58%) who were adherent, nondetectable viral loads were achieved and maintained in 22 (52%). A Kaplan-Meier plot showed a drop-off in patients maintaining a nondetectable viral load after 200 days. Higher initial viral load was the only pretreatment factor that identified adherent patients at risk for treatment failure. Only 3 (10%) nonadherent patients maintained a viral load of <400 copies/ml. The adherent group had a prompt and sustained increase in CD4+ T cell counts. CONCLUSIONS: HAART can achieve control of viral replication in HIV-1-infected children who adhere to therapy. However, treatment failure is likely unless there is a high level of adherence. Nonadherence to therapy is common and might be the major impediment to successful treatment of children infected with HIV-1.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/physiology , Patient Compliance , CD4 Lymphocyte Count , Child , Child, Preschool , HIV Infections/immunology , HIV Protease Inhibitors/therapeutic use , Humans , Infant , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Treatment Outcome , Viral LoadABSTRACT
We sought to determine whether the detectability of phytohemagglutinin-inducible p24 (PHA-p24) in short term cultures of peripheral blood mononuclear cells correlates with an increased risk of vertical transmission among human immunodeficiency virus type 1 (HIV-1)-infected pregnant women and more severe symptomatology among HIV-1-infected infants. The assay for PHA-p24 was performed on specimens obtained from HIV-1-infected women during their pregnancy and from infants during the first 6 months of life. Infants were followed prospectively to determine HIV-1 infection outcome and symptomatology. Among PHA-p24 positive women 9 of 19 (47.4%) gave birth to HIV-1-infected infants compared with 4 of 25 (16.0%) of PHA-p24-negative women (P = 0.02). Among women who tested PHA-p24-positive and had a CD4+ lymphocyte count < 500 cells/mm3, 8 of 15 (53.3%) gave birth to HIV-1-infected infants compared with 4 of 26 (15.4%) not meeting these conditions (P = 0.01). Among HIV-1-infected infants 4 of 5 (80%) of those testing PHA-p24-positive by one month of age developed an opportunistic infection or encephalopathy by 12 months of age, compared with none of the 11 infants testing PHA-p24-negative (P = 0.003). We conclude that PHA-p24 may be a useful in vitro measure for increased risk of vertical transmission among HIV-1-infected pregnant women and increased risk for rapid development of severe disease among HIV-1-infected infants.
Subject(s)
HIV Core Protein p24/blood , HIV Seropositivity/blood , HIV-1 , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/blood , Female , HIV Core Protein p24/biosynthesis , HIV Seropositivity/congenital , HIV Seropositivity/transmission , Humans , Infant , Infant, Newborn , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation , Phytohemagglutinins/pharmacology , PregnancyABSTRACT
BACKGROUND: Risk factors for bacteremia in febrile HIV-infected children are unknown. OBJECTIVE: To describe the frequency of bacteremia in febrile HIV-infected infants and young children in ambulatory settings and its association with clinical and laboratory factors. METHODS: In a birth cohort of 42 HIV-infected children, all febrile outpatient encounters at < or = 36 months of age were reviewed for HIV disease severity, presence of a central venous catheter (CVC) and the usage of antibiotics and/or intravenous immunoglobulin (IVIG). Blood culture results, highest temperature and white blood cell count (WBC) were noted. RESULTS: There was a mean of 1.8 febrile visits (210 visits/116.5 subject years) per child year of observation. Rapid HIV-disease progressors (n=14) were 4 times more likely to have a febrile visit than 28 non-rapid HIV disease progressors (P < 0.01). Blood cultures and WBCs were obtained for 87 and 89% of the febrile visits, respectively. Eleven of the 27 positive blood cultures grew Streptococcus pneumoniae and 16 grew CVC related organisms. The only pathogen identified (n=9) in 104 febrile visits in children without a CVC was S. pneumoniae, which was often (7 of 9) associated with mild illnesses. In children without a CVC temperature > or = 39 degrees C was significantly associated with S. pneumoniae bacteremia (P < 0.05). In 79 febrile visits by subjects with a CVC, temperature > or = 39 degrees C and WBC > or = 15000 cells/mm3 were frequently observed in the 16 bacteremic compared with the 63 nonbacteremic episodes (P < or = 0.05). There was a trend toward fewer S. pneumoniae bacteremias (3 of 11) in febrile subjects who were receiving antibiotics or IVIG. CONCLUSION: HIV-infected children younger than 36 months of age have a high incidence of S. pneumoniae and CVC-related bacteremias. Temperature > or = 39 degrees C, WBC > or = 15000 cells/mm3 and the presence of a CVC should be considered in the management of febrile HIV-infected children.
Subject(s)
Bacteremia/epidemiology , HIV Infections/complications , Pneumococcal Infections/epidemiology , Ambulatory Care , Catheterization, Central Venous/adverse effects , Child, Preschool , Cohort Studies , Female , Fever/epidemiology , Humans , Immunoglobulins, Intravenous/therapeutic use , Incidence , Infant , Leukocyte Count , Male , Streptococcus pneumoniae/isolation & purificationABSTRACT
Enzyme-linked immunosorbent assay polyribosyl ribitol phosphate (PRP) antibody responses to Haemophilus influenzae type b conjugate vaccine (HbOC) given at 2, 4 and 6 months of age were retrospectively compared in 23 human immunodeficiency virus (HIV) and 24 non-HIV-infected infants. HIV-infected infants were divided into those who were P1 (asymptomatic) or P2 (symptomatic) by 1 year of age. The P2 group was further divided into P2A (mildly symptomatic) and > P2A (rapidly symptomatic) by 1 year of age. The post-third HbOC dose geometric mean antibody titer to PRP was significantly lower in 12 P2 infants (0.43 microgram/ml) than either the 11 P1 infants (5.03 micrograms/ml, P < 0.05) or the 24 non-HIV infected infants (3.43 micrograms/ml, P < 0.05). Within the P2 group, the geometric mean antibody titer to PRP was significantly higher in 5 P2A infants (1.63 micrograms/ml) compared with 7 infants who were > P2A (0.17 microgram/ml, P < 0.05). After the third HbOC dose, PRP antibody titers were > or = 1.0 micrograms/ml for 4 of 12 P2 compared with 9 of 11 P1 infants (P < 0.05). Within the P2 group, PRP antibody titers were > 1.0 micrograms/ml for 4 of 5 P2A compared to 0 of 7 infants who were > P2A (P < 0.05). HIV-infected infants with PRP antibody titers > or = 1.0 micrograms/ml after the third HbOC dose had significantly higher mean CD4 counts (2842 cells/mm3) at the time of the third HbOC dose than those with lower PRP titers (1655 cells/mm3) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Antibodies, Bacterial/biosynthesis , Bacterial Proteins/immunology , HIV Infections/immunology , Haemophilus Infections/prevention & control , Haemophilus Vaccines/immunology , Haemophilus influenzae/immunology , Immunoglobulin G/biosynthesis , Polysaccharides/biosynthesis , Bacterial Proteins/administration & dosage , Female , HIV Infections/physiopathology , Haemophilus Infections/immunology , Haemophilus Vaccines/administration & dosage , Humans , Infant , Infant, Newborn , Male , Prognosis , Retrospective Studies , VaccinationABSTRACT
OBJECTIVE: To compare the safety and immunogenicity of a 5-valent pneumococcal conjugate vaccine to a licensed 23-valent polysaccharide pneumococcal vaccine in HIV-infected and non-HIV-infected children > or = 2 years old. METHODS: Thirty HIV-infected and 30 non-HIV-infected children > or = 2 years old were randomized to receive either a 5-valent pneumococcal conjugate vaccine (PCV) or a 23-valent pneumococcal polysaccharide vaccine (PPV) intramuscularly. Children who received PCV initially were given PPV after 6 weeks. Sera were obtained before and at 6 and 12 weeks after the first vaccination to determine IgG pneumococcal antibody titers by enzyme-linked immunosorbent assay to the 5 serotypes represented in the PCV. RESULTS: Both vaccines were well-tolerated with no significant differences in the rates of fever (0 to 14%) or local reactions (0 to 40%) noted between PCV and PPV recipients. Pre-first vaccination geometric mean antibody titers (combined PCV and PPV recipients) to 3 of the 5 pneumococcal types tested were significantly lower in HIV-infected than in non-HIV-infected children (in microgram/ml: type 6B, 0.179 vs. 0.565; type 14, 0.026 vs. 0.060; type 23F, 0.025 vs. 0.119, respectively; P < 0.05). Fewer > or = 4-fold titer rises were observed in HIV vs. non-HIV-infected children whether they received PCV initially (60% vs. 79%, P < 0.05) or PPV (31% vs. 59%, P < 0.05). Also PCV elicited more > or = 4-fold titer rises compared with PPV in HIV-infected (60% vs. 31%, P < 0.05) and non-HIV-infected (79% vs. 59%, P < 0.05) children. No consistent antibody-boosting effect was noted in subjects who received PPV after PCV. CONCLUSIONS: We conclude that antibody responses to natural infection, PCV and particularly PPV are poorer in HIV-infected than in non-HIV-infected children. PCV is as safe as and more immunogenic than the currently licensed PPV among HIV-infected and non-HIV-infected children.
Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Antibodies, Bacterial/blood , Bacterial Vaccines/immunology , Pneumococcal Infections/prevention & control , Polysaccharides/immunology , Vaccination , Vaccines, Conjugate/immunology , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/immunology , Child , Child, Preschool , Consumer Product Safety , Female , Humans , Immunoglobulin G/blood , MaleABSTRACT
Respiratory syncytial virus (RSV) lower respiratory tract and febrile upper respiratory tract illnesses were prospectively assessed in cohorts of 83 infants born to human immunodeficiency virus (HIV)- and of 48 infants born to non-HIV-infected mothers. Of the infants born to HIV-infected mothers, 18 were themselves infected with HIV, 26 were indeterminant and 39 were free from HIV. Ten RSV illnesses occurred in 8 HIV-infected, 2 illnesses in 2 indeterminant and 17 illnesses occurred in 17 non-HIV-infected children. RSV shedding was prolonged in HIV class P2- vs. non-HIV-infected children, at medians of 30 days (range, 1 to 199 days) and 6 days (range, 1 to 21 days), respectively (P = 0.02). Ribavirin and intravenous immunoglobulin failed to eradicate RSV from one child who shed virus for 199 days. Wheezing occurred in 1 of 4 vs. 9 of 10 episodes of lower respiratory tract illness in HIV-infected and non-HIV-infected children, respectively (P = 0.04). No differences were noted in duration of illness, temperature, respiratory rate or oxygen saturation between HIV- and non-HIV-infected children. Infection control and public health concerns regarding prolonged shedding of RSV in HIV-infected children must be recognized.
Subject(s)
AIDS-Related Opportunistic Infections , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human/isolation & purification , Respiratory Tract Infections/microbiology , Bronchiolitis/microbiology , Croup/microbiology , Female , Humans , Infant , Infant, Newborn , Male , Pneumonia/microbiology , Prospective Studies , Respiratory Syncytial Virus Infections/microbiologyABSTRACT
OBJECTIVE: To assess the influence of human immunodeficiency virus (HIV) infection on pregnancy outcome and the effect of pregnancy on the short-term course of HIV infection. METHODS: Pregnant women with identified risk factors for HIV infection but without AIDS were tested serologically for HIV antibodies. Seropositive women were compared to seronegative patients with similar risk factors and demographic characteristics at enrollment, at delivery, and 6-8 weeks postpartum. One hundred one seropositive and 97 seronegative subjects were evaluated for symptoms or physical manifestations of HIV infection; evidence of immune dysfunction; historical, physical, or laboratory evidence of related infections; and maternal and neonatal outcome. Both groups were compared to the entire obstetric population delivering at the University of Maryland Hospital during 1 year. RESULTS: There was a significant reduction in reported risk behaviors in both groups during pregnancy as compared to the period before pregnancy (P < .001). The majority of women in both groups were asymptomatic, but seropositive women were more likely to have a history or physical evidence of condylomata (13 versus 4%; P < .05) and higher temperatures on admission to the labor suite (98.6 +/- 1.0 versus 98.3 +/- 0.8F; P = .02). Seropositive women were not at greater risk for antepartum medical complications. Only one woman developed an AIDS-defining opportunistic infection. Although hematologic indices in seropositive women were abnormal, these did not progress over the course of pregnancy. At delivery, seropositive women were more likely to receive antibiotics (25 versus 10%; P = .006) and less likely to have an episiotomy (25 versus 40%; P = .03), but obstetric outcome was unaffected. Neonatal status was independent of antibody status. CONCLUSION: Our findings support a growing body of evidence that pregnancy has no discernible effect on the early progression of HIV disease in asymptomatic women, and infection does not influence perinatal outcome.
Subject(s)
HIV Seropositivity/complications , Pregnancy Complications, Infectious , Pregnancy Outcome , Adult , CD4-Positive T-Lymphocytes , Female , HIV Seropositivity/immunology , Humans , Leukocyte Count , Pregnancy , Pregnancy Complications, Infectious/immunology , Prognosis , Risk Factors , T-Lymphocytes, RegulatorySubject(s)
HIV Antibodies/analysis , HIV Infections/diagnosis , HIV Seropositivity/diagnosis , HIV-1/immunology , Immunoglobulin A, Secretory/analysis , Saliva/immunology , Age Factors , Blotting, Western , Child , Cohort Studies , Female , Gene Products, env/immunology , HIV Antibodies/blood , HIV Envelope Protein gp120/immunology , HIV Envelope Protein gp160 , HIV Infections/transmission , Humans , Immunoglobulin A, Secretory/blood , Infant , Polymerase Chain Reaction , Prospective Studies , Protein Precursors/immunologyABSTRACT
OBJECTIVE: To assess the safety and immunogenicity of three doses of a five-valent (types 6B, 23F, 14, 18C, and 19F) pneumococcal conjugate vaccine (PCV) among children younger than 2 years who are and are not infected with human immunodeficiency virus (HIV). METHODS: A convenience sample of 18 HIV-infected children 2 years and younger (mean, 12.9 months) received three doses (each separated by 2 months) of PCV. An additional convenience sample of 33 non-HIV-infected children of virtually identical age, race, and sex as the HIV-infected group were randomized in a double-blind fashion to receive three doses of PCV or saline placebo. Safety data were collected for 72 hours after each vaccination. Sera were obtained before each and 1 month after the third vaccination to determine vaccine type-specific immunoglobulin G pneumococcal antibody titers by an enzyme-linked immunosorbent assay. RESULTS: Seventeen HIV- and 30 non-HIV-infected children completed the study. The PCV was well tolerated by both HIV- and non-HIV-infected children. No significant differences in local or systemic reactions were noted between HIV- and non-HIV-infected PCV or placebo recipients. Three doses of PCV were immunogenic, as evidenced by 16- to 659-fold increases in type-specific geometric mean antibody titers over prevaccination levels in HIV- and non-HIV-infected children. With respect to an arbitrary protective level, 78% of the antibody titers from HIV-infected children and 88% of the titers from non-HIV-infected children were 1.0 microgram/mL or greater 1 month after the third PCV dose. HIV-infected children with milder disease (Centers for Disease Control and Prevention classes N1-2, A1-2, and B1) were more likely to have protective antibody titers after the first and second PCV doses than HIV-infected children with more advanced disease (Centers for Disease Control and Prevention classes N3, A3, B2-3, and C1-3). However, after the third PCV dose, these differences disappeared. CONCLUSION: Three doses of PCV seem safe and immunogenic in both HIV- and non-HIV-infected children younger than 2 years. This type of vaccine should result in a marked reduction in systemic pneumococcal disease in both HIV- and non-HIV-infected children. Given the high incidence of invasive pneumococcal disease in HIV-infected children, this vaccine may markedly improve the quality of life for this unfortunate group of children.
Subject(s)
AIDS-Related Opportunistic Infections/immunology , Bacterial Vaccines/immunology , HIV Infections/immunology , Pneumococcal Infections/immunology , Pneumococcal Vaccines , Bacterial Vaccines/adverse effects , Humans , Infant , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/immunologyABSTRACT
OBJECTIVE: To describe the incidence and clinical presentation of invasive pneumococcal disease in a cohort of children infected with human immunodeficiency virus (HIV) who were prospectively followed from birth, in comparison with uninfected children born to HIV-infected mothers and control children. DESIGN: Prospective follow-up of a cohort recruited at birth and born to mothers with known HIV status. The person-years analysis method used the occurrence of invasive pneumococcal disease as the end point. SETTING: Hospital-based clinic specializing in care of HIV-at-risk and HIV-infected children in Baltimore, Md. PARTICIPANTS: Forty-one vertically HIV-infected children, 128 uninfected children born to HIV-infected mothers, and 71 control children born to mothers with negative findings for HIV but with HIV risk factors. RESULTS: Among HIV-infected children, 10 episodes of invasive pneumococcal disease occurred during the first 36 months of life compared with 4 episodes among uninfected children and 1 episode among control subjects. The relative risk for HIV-infected children versus the combined uninfected and control groups was 12.6 with a 95% confidence interval (5.4, 28.8) and a p value for difference between groups of < 0.001. The incidence rate per 100 child-years of observation during the first 36 months of life was 11.3 for HIV-infected, 1.1 for uninfected, and 0.5 for control children. Clinical and laboratory variables were not useful in identifying HIV-infected children at risk for pneumococcal disease. CONCLUSION: Practical strategies to prevent pneumococcal disease among HIV-infected children need to be developed.
Subject(s)
HIV Infections/congenital , HIV Infections/complications , HIV-1 , Pneumococcal Infections/etiology , Sepsis/etiology , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Infant , Pneumococcal Infections/epidemiology , Prospective StudiesABSTRACT
OBJECTIVE: To examine the presentation, course, and outcome of pneumococcal bacteremia in children infected with human immunodeficiency virus (HIV). METHODS: A retrospective series of HIV-infected children less than 18 years of age with Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was evaluated. The main outcome measures included persistent bacteremia, the development of a focal infection, and death. RESULTS: Seventy-two episodes of pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or = 10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia, age >3 years old was associated with a lower mean WBC count compared with episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.) were less likely than patients without antibiotic treatment to have persistent bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient with occult bacteremia died, progressed to clinical meningitis, or had other sequelae. Two of fifty-four patients died as a result of their first episode of invasive pneumococcal disease. Both patients who died had meningitis and appeared ill on initial presentation. CONCLUSIONS: Neither a WBC count > or = 15,000 nor > or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected children. Empiric antibiotics are useful to decrease the risk of persistent bacteremia. Children infected with HIV who have occult pneumococcal bacteremia appear to do well with appropriate antibiotics. Patients who are afebrile and well appearing on reevaluation may be safely treated as outpatients.
Subject(s)
AIDS-Related Opportunistic Infections , Bacteremia , Pneumococcal Infections , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Bacteremia/complications , Bacteremia/diagnosis , Bacteremia/drug therapy , Child , Child, Preschool , Humans , Infant , Leukocyte Count , Pneumococcal Infections/complications , Pneumococcal Infections/diagnosis , Pneumococcal Infections/drug therapy , Sensitivity and SpecificityABSTRACT
This paper presents findings of a multi-site study designed to document: (1) caregivers' regimen knowledge; (2) barriers to adherence; and (3) the relationships between adherence, regimen knowledge and barriers. Fifty-one predominantly female, African American parents and caregivers of HIV-infected children completed the Treatment Interview Protocol (TIP), a brief, structured interview designed to assess regimen knowledge and barriers to adherence. TIP data were compared to information obtained from medical records and pharmacy refill histories. Forty-nine per cent of children were considered adherent, defined as > or = 90% refill rate, which was significantly associated with virologic response. Significant regimen knowledge deficits were observed among caregivers, and inaccurate identification of prescribed medications was significantly associated with adherence. Caregivers identified 21 barriers to adherence, and poor adherence was significantly related to the number of barriers reported. Results indicate that the TIP is a successful tool for identifying regimen knowledge, potential adherence barriers and adherence problems. Results suggest that the TIP could be integrated into clinical practice as a quick, effective tool to identify poor adherers and guide interventions and treatment decision making.
Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/psychology , HIV Infections/drug therapy , Patient Compliance , Caregivers , Child , Child, Preschool , Drug Monitoring , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Parents , Reproducibility of Results , Viral Load/methodsABSTRACT
BACKGROUND: Neurodevelopmental impairment has been identified in children infected with human immunodeficiency virus (HIV). The frequency and spectrum of neurologic impairment are greater in children than those reported for adults. In children, HIV is known to enter the central nervous system early in the course of the disease. The presentation of pediatric neuro-acquired immune deficiency syndrome ranges from static (eg, nonprogressive developmental delay) to progressive encephalopathy (eg, acquired microcephaly, pyramidal tract signs, and spasticity). It has been demonstrated that antiretroviral agents can improve or even reverse the course of neurologic impairment in children. These changes have been attributed to various degrees of central nervous system drug penetration. Increasingly, protease inhibitors and combination antiretroviral therapy using reverse transcriptase inhibitors are being used in the treatment of children infected with HIV. The addition of a protease inhibitor to nucleoside analogue therapy has been reported to delay disease progression and prolong life in adults with moderate to advanced HIV disease. No data currently exist on the impact of combination therapy using two nucleoside analogues and a protease inhibitor on neurodevelopmental and neurologic function in children with HIV infection. The following case report presents the effects of combination therapy using ritonavir in a child infected with HIV. CASE REPORT: An 8-year, 2-month-old African-American boy was infected with HIV through vertical transmission. Regular monitoring of the patient's neurodevelopmental status has been conducted as part of his participation in longitudinal research protocols. For the first 51/2 years of life, his neurodevelopmental status was normal, with cognitive functioning as measured by standardized psychometric tools solidly in the average range. Speech and language skills were age-appropriate. Tests of gross and fine motor functioning as well as evaluation of overall neurodevelopmental status suggested normal development. Magnetic resonance imaging (MRI) of the brain was consistently normal. His family reported that adaptive functioning, peer and family relationships, and behavior were all within normal limits. School reports indicated consistently that the patient was performing at age and grade level, with respect to both academic achievement and behavior. Initial concerns regarding the patient's development were expressed by both his family and school at age 6 years, 6 months. These concerns included difficulty with classroom work, decreased attention, word-finding problems, fatigue, staring spells, and loss of strength. His family and school reported a marked loss of skills acquired previously. Results of formal psychological and speech and language evaluation reflected statistically significant drops in test scores from baseline, with both delayed and atypical skills evident. The patient's condition worsened rapidly. Within a few months, he was no longer able to use sentences to communicate. Cognitive testing was attempted, but he was unable to participate because of significant fatigue, limited attention, and inability to communicate verbally. His family described periods of disorientation and confusion, lethargy, and disinterest in age-appropriate activities. He became agitated and overstimulated easily both in small group settings and in crowds. He demonstrated both fine and gross motor impairments. When frustrated, he displayed infantile and autistic-like behavior. MRI with contrast showed diffuse atrophy as well as mild prominence of the ventricles and sulcii compared with baseline assessment. In addition to fatigue and neurologic symptoms, wasting syndrome was diagnosed, with loss of percentiles in both weight and height by age 71/2 years. Low-grade elevation of liver function tests and amylase was noted. Blood cultures for mycobacteria were negative, as were serologic tests for hepatitis. (ABSTRACT TRUN
Subject(s)
AIDS Dementia Complex/drug therapy , Anti-HIV Agents/therapeutic use , Brain/physiopathology , HIV Protease Inhibitors/therapeutic use , Ritonavir/therapeutic use , AIDS Dementia Complex/diagnosis , AIDS Dementia Complex/physiopathology , AIDS Dementia Complex/transmission , Brain/pathology , CD4 Lymphocyte Count , Child , Cognition Disorders/physiopathology , Drug Therapy, Combination , Humans , Infectious Disease Transmission, Vertical , Lamivudine/therapeutic use , Magnetic Resonance Imaging , Male , Psychological Tests , Virus Replication/drug effects , Zidovudine/therapeutic useABSTRACT
The objective of this study was to examine vaccine type-specific antibody titers eight months after a five-valent pneumococcal conjugate vaccine (PCV) in human immunodeficiency virus (HIV) and non-HIV-infected children under two years of age. Sixteen HIV-infected and 14 non-HIV-infected children under two years of age, and of similar age, race and sex distribution, received three doses (separated by two months each) of a five-valent oligosaccharide PCV (types 6B, 14, 18C, 19F, and 23F separately coupled to diphtheria CRM197). An additional 11 non-HIV-infected children, of similar demographic distribution to the PCV groups, received three doses of saline placebo. sera were collected just prior to, and at one and eight months after the three study drug doses. Serum vaccine type-specific pneumococcal IgG antibodies were measured by enzyme-linked immunoabsorbant assay (ELISA). There was an impressive rise in antibody titers pre- to one month post-third PCV in both the HIV (58-970-fold) and non-HIV-infected (19-553-fold) children. There was a rapid and similar drop in antibody titers eight months after the PCV series for both HIV (range 69-87% drop) and non-HIV-infected (range 57-79% drop) subjects respectively. However, 46% of the antibody titers from HIV-infected children and 62% of the titers from non-HIV-infected children were still > 1.0 microgram ml-1 compared to placebo recipients for whom only 5% of the titers were > 1.0 microgram ml-1 (p < 0.05). At the eight month post-PCV series blood draw, there were no significant differences in the GMTs, the percent drop in titers, or proportion of titers > 1.0 microgram ml-1 between the five HIV-infected children who had advanced (CDC class: N3, A3, B2-3, C1-3) compared to the 11 children with mild (CDC class: N1-2, A1-2, B1) HIV disease at the time of their first PCV dose. Eight months after the PCV series, the proportion of titers (combined all five serotypes) > 1.0 microgram ml-1 was slightly, but significantly, lower for HIV-infected subjects (46%) compared to non-HIV-infected subjects (62%) (p < 0.05). These data are helpful in describing the kinetics of antibody responses to pneumococcal conjugate vaccines in both HIV and non-HIV-infected young children.
Subject(s)
Bacterial Vaccines/immunology , HIV Infections/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Bacterial Vaccines/administration & dosage , Female , Humans , Immunoglobulin G , Infant , Male , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunologyABSTRACT
Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes. There was a wide range (0. 16-30.80 microg/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 microg/mL (n=34). Seventy-six percent of the antibody values were <2.0 microg/mL, and 95% were <5.0 microg/mL. Homologous seroresponses (>/=4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders.