Perinatally Acquired Human Immunodeficiency Virus Research Articles

Plasma Lipidomic Profiles in cART-Treated Adolescents with Perinatally Acquired HIV Compared to Matched Controls.

Children with perinatally acquired human immunodeficiency virus (PHIV) are growing into adulthood with HIV and treatment-associated comorbidities, such as dyslipidemia and insulin resistance. HIV is identified as independent risk factor for cardiovascular disease (CVD). The hypothesis behind increased CVD risk associated with HIV includes vascular inflammation, dyslipidemia and combination antiretroviral therapy (cART) metabolomic toxicity. To investigate differences in lipid profiles and pathophysiological mechanisms of CVD risk in adolescents with PHIV, we compared the plasma lipidome of PHIV adolescents and HIV-negative controls. We additionally investigated the influence of current cART regimens and increased lipoprotein(a) (Lp(a)) levels on the plasma lipidome. We included 20 PHIV-infected adolescents and 20 HIV-negative controls matched for age, sex, ethnic origin and socio-economic status. Plasma lipidome was measured using Thermo Scientific Ultimate 3000 binary high-performance liquid chromatography (HPLC)-mass spectrometry. We evaluated the plasma lipidome in PHIV adolescents using different cART regimens (including those known to be associated with lipid alterations). The median age was 17.5 years (15.5-20.7) and 16.5 years (15.7-19.8) for PHIV adolescents and controls, respectively. Of PHIV adolescents, 45% used a non-nucleotide reverse transcriptase inhibitor (NNRTI)-based (25%) or protease inhibitor (PI)-based (20%) cART regimen. In this pilot study, we observed no significant differences between lipidomic profiles between PHIV adolescents and controls. We observed no differences in the plasma lipidome in participants with increased versus normal Lp(a) levels. Different cART regimens appear to influence chain length differences in the plasma lipidome of PHIV adolescents; however, the significance and causality of this observation remains undetermined. Further research on the influence of cART on lipid composition could further identify these alterations.

Factors Associated with Morbidity and Mortality Among Sexually Active Asian Adolescents and Young Adults with Perinatally Acquired HIV.

We assessed morbidity and mortality among Thai and Vietnamese adolescents and young adults with perinatally acquired human immunodeficiency virus (PHIV) compared with matched HIV-negative peers, 12-24 years of age. Data on serious adverse events (SAEs) were prospectively collected between 2013 and 2018 according to U.S. NIH Division of AIDS criteria. Of 288 youth, 142 had PHIV and 146 were HIV negative. At enrollment, the overall median age was 19 (interquartile range [IQR] 17-20) years, 67% were female, and 95% were Thai. Almost all PHIV youth (99%) were receiving antiretroviral therapy; 50% self-reported adherence ≥95%. Median CD4 was 579 (IQR 404-800) cells/mm3, and 24% had HIV-RNA ≥1,000 copies/mL. During follow-up, 31 (22%) PHIV youth and 9 (6%) HIV-negative youth had at least one SAE. The overall crude SAE rate was 4.66 (3.42-6.35) per 100 person-years (PY); 7.22 (5.08-10.26) per 100 PY among youth with PHIV and 2.10 (1.09-4.03) per 100 PY in HIV-negative youth (p < .001). All seven deaths that occurred were among those with PHIV and primarily due to opportunistic infections (e.g., pneumocystis pneumonia, tuberculous meningitis). In multivariate analyses, having PHIV, being <20 years of age, and having anogenital high-risk human papillomavirus (HPV) infection with types 16 and/or 18 increased risk of SAEs. Among PHIV youth, CD4 count <350 cells/mm3, HIV-RNA ≥1,000 copies/mL, advanced WHO stages, and having anogenital HPV 16 and/or 18 infection predicted higher incidence of SAEs; no prior use of alcohol was protective. These data emphasize the need for tailored interventions for adolescents with PHIV to prevent long-term morbidity and mortality.

Plasma Neurofilament Light Is Not Associated with Ongoing Neuroaxonal Injury or Cognitive Decline in Perinatally HIV Infected Adolescents: A Brief Report.

Despite combination antiretroviral therapy (cART), adolescents with perinatally acquired human immunodeficiency virus (PHIV) exhibit cerebral injury and cognitive impairment. Plasma neurofilament light (pNfL) is a biomarker identified as a promising marker associated with neuroaxonal injury and cognitive impairment. To investigate whether cerebral injury in cART-treated PHIV adolescents is persistent, we longitudinally measured pNfL. We included 21 PHIV adolescents and 23 controls, matched for age, sex, ethnic origin and socio-economic status. We measured pNfL in both groups and CSF NfL in PHIV adolescents using a highly sensitive Single Molecule Array (Simoa) immunoassay. We compared pNfL between groups over time with a mean follow-up time of 4.6 years and assessed its association with MRI outcomes, cognitive function and HIV-related characteristics using linear mixed models. The median age was 17.5 years (15.5–20.7) and 16.4 years (15.8–19.6) at the second assessment for PHIV adolescents and controls, respectively. We found comparable pNfL (PHIV vs. controls) at the first (2.9 pg/mL (IQR 2.0–3.8) and 3.0 pg/mL (IQR 2.3–3.5), p = 0.499) and second assessment (3.3 pg/mL (IQR 2.5–4.1) and 3.0 pg/mL (IQR 2.5–3.7), p = 0.658) and observed no longitudinal change (coefficient; −0.19, 95% −0.5 to 0.1, p = 0.244). No significant associations were found between pNfL and HIV- or cART-related variables, MRI outcomes or cognitive function. We observed low CSF NfL concentrations at the baseline in PHIV adolescents (100.8 pg/mL, SD = 47.5). Our results suggest that there is no ongoing neuroaxonal injury in cART-treated PHIV adolescents and that the neuroaxonal injury is acquired in the past, emphasizing the importance of early cART to mitigate HIV-related neuroaxonal damage.

Levels of vaccination coverage among HIV-exposed children in China: a retrospective study

BackgroundVaccination is crucial for human immunodeficiency virus (HIV)-exposed children because of their increased risk of morbidity and mortality from various vaccine-preventable diseases. However, studies have shown that they are at high risk of incomplete vaccination. Although China has developed prevention of mother-to-child transmission (PMTCT) of HIV programs substantially over the past decades, few studies have investigated the immunization levels of Chinese HIV-exposed children. Therefore, we aimed to evaluate vaccination coverage and its associated factors among HIV-exposed children in China during 2016‒2018.MethodsWe conducted a retrospective cohort review of all cases of Chinese HIV-exposed children born between July 1, 2016 and June 30, 2018 recorded in the Chinese information system on PMTCT. The vaccination coverage indicators refer to the percentage of children who received recommended basic vaccines, including Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), polio, measles-containing vaccine (MCV), and diphtheria-tetanus-pertussis-containing (DTP) vaccine. Univariate and multivariate logistic regression analyses expressed as crude odds ratios (cORs) and adjusted odds ratios (aORs), each with 95% confidence intervals (95% CI), were performed to compare the proportional differences of factors associated with vaccine coverage.ResultsAmong the enrolled 10 033 children, the vaccination rate was 54.1% for BCG, 84.5% for complete HepB vaccination, 54.5% for complete polio vaccination, 51.3% for MCV, and 59.5% for complete DTP vaccination. Children with perinatally acquired HIV (PHIV) were 2.46‒3.82 times less likely to be vaccinated than HIV-exposed uninfected children. Multivariate logistic regression indicated that children of Han ethnicity (aOR = 1.33‒2.04), children with early infant diagnosis (EID) of HIV (aOR = 1.86‒3.17), and children whose mothers had better education (college or above, aOR = 1.63‒2.51) had higher odds of being vaccinated. Most of the deceased children (aOR = 4.28‒21.55) missed vaccination, and PHIV (aOR = 2.46‒3.82) significantly affected immunization.ConclusionsChinese HIV-exposed children had low vaccination coverage, which is a serious health challenge that needs to be addressed thoroughly. Interventions should be developed with a focus on minority HIV-exposed children whose mothers do not have formal education. Particularly, more attention should be paid to EID to increase access to immunization.Graphical abstract

Novel Adherence Interventions in Perinatally Acquired HIV: PEG Insertion and Pill Glide.

Children, adolescents and young adults (CAYA) with perinatally acquired human immunodeficiency virus (PaHIV) need lifelong antiretroviral therapy (ART) to suppress viral load (VL), maintain health and prevent onward transmission. Many struggle with adherence despite multidisciplinary input. We assessed ART adherence outcomes following two novel interventions: percutaneous endoscopic gastrostomy (PEG) and Pill Glide®, a fruit-flavoured lubricant spray aiding tablet swallowing. Retrospective cohort analysis by database and case-note review of PaHIV CAYA aged < 25years receiving PEG or Pill Glide® between 1995 and 2017 at a single tertiary centre. Nineteen PEGs were inserted in 15 CAYA at a median age of 17 (IQR 6-22) years, median CD4 count 40 cells/µL (IQR 10-220). A viral load (VL) < 50 copies/mL was achieved in 93% with PEG ART. At last follow-up all were alive, median age 23years (IQR 22-28). Nine had PEG removed, after a median of 3.3years (range 0.5-6.8), with a current VL < 50 copies/mL, median CD4 count 940 cells/µL (IQR 261-1353) sustained post PEG removal median was 5.4years (range 1.5-17.8) previously. From 2017 seven CAYA received Pill Glide®, median age 10years (IQR 7-14), median CD4 count 898 cells/µL (range 148-1943), 6/7 with a suppressed VL. All reported increased ease in tablet swallowing and transitioned successfully from crushed tablets/liquids to tablets. At follow-up, all patients had a suppressed VL. Whilst PEG insertion markedly improved rates of viral suppression in CAYA struggling with ART adherence, the use of novel less invasive aids such as Pill Glide® requires further exploration.

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa.

Despite the undisputed benefits of combination antiretroviral therapy (cART), perinatally acquired human immunodeficiency virus (PHIV) children on treatment often present with a spectrum of neurological deficits known as HIV-associated neurocognitive impairment. Even higher CD4 cell count does not seem to prevent the development of neurocognitive impairment in children with PHIV. While CD4 cell count has shown to have the greatest prognostic value, its association with neurocognitive abilities remains to be clarified. This study aimed at determining the correlation between plasma CD4+ lymphocyte and neurocognitive function in children with PHIV on cART. In total, 152 purposively recruited hospital-based sample of children with PHIV on cART, aged 3 years to 7 years 6 months (mean age, 63.13 months), underwent neurocognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Immunological status of each child was based on the plasma CD4+ lymphocyte levels. The mean CD4+ lymphocyte cell count at the time of neurocognitive assessment was 1,259.85 cells/mm3 (mean range, 139–2,717 cells/mm3), with significant age difference on CD4+ lymphocyte count levels [F(2, 149) = 13.58, p = 0.000]. CD4+ lymphocyte counts was significantly correlated with subdomains of neurocognitive function scores of task that measures working memory, processing speed, and perceptual reasoning. Global cognitive ability (Full Scale Intellectual Quotient) had no significant association with immunological status of the children. The findings support an association between immunological status of PHIV infection and executive function task. These neurocognitive faculties are critical for learning, school readiness and success in early childhood, and ultimately treatment adherence in adolescence. The need for early identification of neurodevelopment deficits in children, even when on cART, is crucial because early psychosocial and neurorehabilitative interventions can lead to better outcome for children with PHIV.

Incidence and Persistence of High-risk Anogenital Human Papillomavirus Infection Among Female Youth With and Without Perinatally Acquired Human Immunodefiency Virus Infection: A 3-year Observational Cohort Study.

Female youth with perinatally acquired human immunodeficiency virus (PHIV) may be at higher risk than uninfected youth for persistent anogenital human papillomavirus (HPV) infection, due to prolonged immunodeficiency. A 3-year cohort study was conducted between 2013 and 2017 among Thai and Vietnamese PHIV and HIV-uninfected females 12-24 years, matched by age group and number of lifetime sexual partners. For HPV genotyping, cervical and anal samples were obtained at baseline and annually. Vaginal samples were collected at baseline and every 6 months. Factors associated with high-risk HPV (HR-HPV) persistence and incidence were assessed. We enrolled 93 PHIV and 99 HIV-uninfected females. Median age was 19 (interquartile range [IQR] 18-20) years. For the 7 HR-HPV types (16, 18, 31, 33, 45, 52, 58) in the nonavalent HPV vaccine, PHIV had significantly higher incidence (P = .03) and persistence (P = .01) than HIV-uninfected youth over a 3-year period. Having HIV (adjusted hazard ratio [aHR] 2.1, 95% confidence interval [CI] 1.1-3.9) and ever using illegal substances (aHR 4.8, 95% CI 1.8-13.0) were associated with incident 7 HR-HPV infections. HIV-positive status (adjusted prevalence ratio [aPR] 2.2, 95% CI 1.5-3.2), recent alcohol use (aPR 1.75, 95% CI 1.2-2.5), and higher number of lifetime partners (aPR 2.0, 95% CI 1.4-3.1, for 3-5 partners; aPR 1.93, 95% CI 1.2-3.2, for ≥6 partners) were significantly associated with persistent 7 HR-HPV infections. Female PHIV were at higher risk of having anogenital HR-HPV acquisition and persistence. Primary and secondary prevention programs for HPV infection and HPV-related diseases should be prioritized for PHIV children and youth.

Symptom Profiles of CD and ODD Among Youth With Perinatally Acquired HIV.

Youth with perinatally acquired human immunodeficiency virus (PHIV) face increased risk for conduct disorder (CD) and oppositional defiant disorder (ODD) symptoms, and heterogeneous findings indicate that there may be subgroups of youth with PHIV differing in the quality and/or frequency of symptoms. The present study examined symptom profiles of CD and ODD among youth with PHIV and whether profiles differed in terms of parent-child and family correlates. Participants included 314 youth with PHIV, aged 6-17 years (M = 12.88 years, SD = 3.08; 51% male; 85% Black or Latinx), and their caregivers who were recruited from 29 clinics in the US involved in the International Maternal Pediatrics Adolescent AIDS Clinical Trials (IMPAACT) Group's P1055 study. Caregivers reported on youth CD and ODD symptoms, parent-child interactions, and family environment. Latent class analysis indicated that a four-class model (i.e., moderate CD/high ODD, high ODD, moderate ODD, low CD/ODD) best fit the data. Ancillary analyses to validate these classes revealed differences for family cohesion and conflict; and child-centeredness, detachment, guilt-induced control, and consistency in parent-child interactions. The low CD/ODD class generally differed from other classes with additional differentiation between some higher risk profiles. Findings suggest that homogeneous classes of CD/ODD symptoms can be identified among youth with PHIV, and these profiles differ in terms of family processes, consistent with previous work among chronically ill youth.

Prevalence of Systemic Hypertension Among HIV-Infected and HIV-Uninfected Young Adults in Baltimore, Maryland.

Adults with perinatally acquired human immunodeficiency virus (PHIV) infection may be at increased risk for nonacquired immunodeficiency syndrome (AIDS) diseases, including systemic hypertension (HTN). The purpose of this study was to examine the prevalence of HTN among young adults with PHIV compared with recently infected and uninfected young adults. We conducted a cross-sectional study of young adults with PHIV, frequency matched on race and sex to a stratified random sample of young adults with nonperinatally acquired HIV (NPHIV) and HIV-uninfected young adults. All of the subjects were aged 18 to 29 years. HTN was defined as two systolic blood pressure measurements ≥140 mm Hg or diastolic ≥90 mm Hg at least 3 months apart and/or prescription for an antihypertensive medication. Logistic regression was used to estimate adjusted prevalence odds ratios and 95% confidence intervals (CIs) for the association between HIV infection and HTN. A total of 324 patients were included-108 per exposure group. The prevalence of HTN was 23% among individuals with PHIV, 10% among individuals with NPHIV, and 8% among HIV-uninfected patients. PHIV patients had 3.4 (95% CI 1.48-7.66) times the base odds of having HTN compared with HIV-uninfected patients, and 2.7 (95% CI 1.23-5.71) times the odds compared with NPHIV patients. By multivariable analysis, PHIV patients had 4.7 and 2.9 times the odds of having HTN compared with HIV-uninfected patients and NPHIV patients, respectively, after controlling for sex, race, and family history of hypertension. Our findings suggest that HTN prevalence among PHIV young adults is significantly higher than sex- and race-matched NPHIV and HIV-uninfected patients of similar age.

Overt acquired primary hypothyroidism in a ten-year-old girl with perinatally-acquired HIV infection on HAART: A rare association

Overt hypothyroidism is rare in human immunodeficiency virus (HIV)-infected children but can further compromise the child’s quality of life. We report a case of a 10-year-old girl with perinatally-acquired human immunodeficiency virus (HIV) infection who subsequently developed overt acquired primary hypothyroidism. She has been on highly active antiretroviral therapy (HAART) for 9 years but developed goitre 2 years before presentation. Her thyroid gland was diffusely enlarged, firm, freely movable and non-tender. She had no symptoms of hypo- or hyperthyroidism. Physical examination revealed periorbital puffiness. Although her height was 139cm (50th percentile), it was significantly below the target centile range (152.5- 169.5cm). Results of investigations showed very low free T4 and markedly elevated TSH level (31-fold increase above our laboratory reference value). Ultrasonography of the goitre showed multicystic nodules in both lobes. She was commenced on oral levo-thyroxine 100μg once daily.&#x0D; Conclusion: Physicians need to pay more attention to thyroid function in HIV-infected children on HAART, particularly in the presence of linear growth abnormalities.&#x0D; Bangladesh Journal of Medical Science Vol.18(2) 2019 p.411-415

Unexpectedly High Prevalence of Cytomegalovirus DNAemia in Older Children and Adolescents With Perinatally Acquired Human Immunodeficiency Virus Infection.

BackgroundOlder children and adolescents with perinatally acquired human immunodeficiency virus (PHIV) infection in Africa experience multiple comorbidities that are not typical of HIV-associated opportunistic infections, including growth impairment and chronic lung disease. We examined associations between plasma cytomegalovirus (CMV) DNA and lung function and growth.MethodsPlasma CMV DNA loads were measured children aged 6–16 years with PHIV (n = 402) and HIV-uninfected controls (n = 224). The HIV-infected children were either newly diagnosed or known HIV infected and stable on antiretroviral therapy (ART) for >6 months. CMV DNA loads were measured using quantitative polymerase chain reaction. CMV DNAemia was modeled as a time-varying outcome using longitudinal mixed-effects logistic regression.ResultsAt enrollment, CMV DNAemia ≥1000 copies/mL (defined as “clinically significant”) was detected in 5.8% of uninfected children, 14.7% of HIV-infected participants stable on ART, and 22.6% of HIV-infected ART-naive children (χ2 = 23.8, P < .001). The prevalence of CMV DNAemia ≥1000 copies/mL was associated with CD4 counts <350 cells/µL. Among HIV-infected ART-naive children, the presence of CMV DNAemia of ≥1000 copies/mL was independently associated with reduced lung function (adjusted odds ratio [aOR] = 3.23; 95% confidence interval [CI], 1.23–8.46; P = .017). Among ART-treated children, stunting was associated with CMV DNAemia of ≥1000 copies/mL (aOR = 2.79; 95% CI, 0.97–8.02; P = .057).ConclusionsClinically significant levels of CMV DNAemia were common in older children with PHIV, even those on ART, suggesting a role for inadequately controlled CMV infection in the pathogenesis of PHIV comorbidities in Africa.

Profiles of caregiving behaviors among children and adolescents with perinatally acquired HIV

ABSTRACTAlthough parenting behaviors are widely considered an important factor in the adjustment of children and adolescents with chronic physical health needs, few studies have addressed this topic as it pertains to youth with perinatally-acquired human immunodeficiency virus (PHIV). We examined profiles of child-centeredness, control through guilt, consistent discipline, and detachment, and whether these profiles differed in terms of parent- and youth-reported psychiatric disorder symptoms in a cohort of HIV infected youth (N = 314). Latent profile analyses of caregiving behaviors were conducted separately for children (6–12 years) and adolescents (13–18 years). Two profiles were identified among children: (a) moderate caregiving (87%, n = 130) and (b) high detachment caregiving (13%, n = 19), and three profiles were identified among adolescents: (a) moderate caregiving (55%, n = 88), (b) high detachment caregiving (19%, n = 30), and (c) high control through guilt caregiving (26%, n = 42). The high detachment and high control through guilt caregiving profiles displayed higher levels of parent-and youth-reported symptoms than the moderate caregiving profile. These findings suggest that caregiver behaviors of PHIV youth vary as a function of children’s developmental period and differ in terms of youth psychological symptoms.

Identifying preventable causes of mortality among pregnant women living with perinatally-acquired human immunodeficiency virus

Identifying preventable causes of mortality among pregnant women living with perinatally-acquired human immunodeficiency virus

Premature Coronary Artery Disease and ST-Elevation Myocardial Infarction in a 24-Year-Old Man With Perinatally Acquired Human Immunodeficiency Virus: A Case Report.

Patients with human immunodeficiency virus (HIV) have increased risk of cardiovascular disease. Although evidence of subclinical atherosclerosis in perinatally acquired HIV (PHIV) is available, myocardial infarction has not been described in this population. We report a case of myocardial infarction in a patient with PHIV with a brief literature review.

Disease disclosure, treatment adherence, and behavioural profile in a cohort of vertically acquired HIV-infected adolescents. NeuroCoRISpeS study

ABSTRACTAdvances in care and antiretroviral treatment, improved life expectancy and quality of life in children with perinatally-acquired human immunodeficiency virus (HIV) infection. There is increasing interest in the chronic effects of growing up with HIV. The aim of this study was to assess the psychosocial, emotional and behavioural functioning in a cohort of perinatally-acquired HIV-infected adolescents. Data were obtained through semi-structured interviews and the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural disorders screening. Results: A total of 95 patients (58% women) were assessed with a median age of 15 years (11–19.1) and a median age at diagnosis of 1.7 years (0–12.2). The median CD4 count, at the inclusion, was 626 cells/mm3 (132–998), with 34% (10–52%). Viral load was <50 copies/ml in 72% of patients. Eighty-one per cent knew their diagnosis and optimal adherence was achieved in 53%. Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers had a complete and adequate knowledge of their disease and only 18.2% had shared it with their friends. Six unwanted pregnancies occurred (11% of women). Most of them (90%) attended school but 60% had been held back one or more school years. Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The report of behaviours associated with hyperactivity was high in 14.9% of the population and borderline in 18.1%. Adolescents with encephalopathy accounted for 44% of those whose total scores fell in either the abnormal and borderline ranges for emotional difficulties (p = .038). Conclusion: Perinatally-acquired HIV-infected adolescents showed significant psychosocial and behavioural health risks that should bring attention to prevention and health care programmes. An earlier disclosure to children could favour a better psychological adjustment and a better treatment adherence. Future studies are needed to assess the relationship between vertically acquired HIV-infection and hyperactivity.

Older Children and Adolescents Living With Perinatally Acquired Human Immunodeficiency Virus Infection

To describe the clinical, immunologic, and psychosocial characteristics of children living with perinatally-acquired human immunodeficiency virus (HIV) infection beyond the age of 9 years. This is a descriptive cohort study of 42 surviving perinatally infected children older than 9 years followed at the Children's Hospital Acquired Immunodeficiency Syndrome (AIDS) Program (part of a university-based inner city medical center) as of June 1993. The study is based on medical record data of clinical, immunologic, and psychosocial parameters. The cohort includes 20 boys and 22 girls with a mean age of 136 months. The mean age at diagnosis of HIV infection was 88 months, and 59.5% were asymptomatic at the time of diagnosis. Currently, after a mean follow-up period of 48 months from diagnosis, 23.8% remain asymptomatic, 19.1% have non-AIDS-defining HIV-related symptoms, and 57.1% have AIDS; 85.7% of the cohort did not develop HIV-related symptoms until after 48 months of age (late-onset prolonged survivors). There was an average annual decline of 71.4 CD4+ cells/microL in the cohort from the ages of 7 to 16 years, and 21.4% have a current CD4+ lymphocyte count of greater than 500 cells/microL, 28.6% between 200 and 500 cells/microL, and 50% less than 200 cells/microL; 76% are orphaned as a result of maternal death, with the majority of the cohort (60%) cared for by extended family members. Disclosure of diagnosis has occurred in 57.1%. The vast majority of the cohort (76%) are attending regular school, with the remainder in special education. Although close to one quarter of the children and adolescents ages 9 to 16 years living with perinatally acquired HIV infection described in this cohort remain asymptomatic and have a relatively intact immune system, the remainder are living with significant HIV-related symptoms, many of which are chronic in nature and have an impact on daily living. The children in this cohort had both significant immunologic deterioration and symptomatic disease progression during the mean follow-up period of 48 months from the time of diagnosis with HIV infection.