Pediatric HIV Disease Research Articles

Exploring Factors Associated with Quality of Life in Caregivers of Children and Adolescents with Sickle Cell Disease and HIV: A Comparative Analysis.

Paediatric HIV and sickle cell disease (SCD) are two stigmatising and potentially fatal illnesses that place a significant burden on families. HIV patients benefit from a longstanding free-service national programme in Cameroon, and this could considerably alleviate burden of care on HIV caregivers, possibly leading to better quality of life (QoL) in HIV caregivers compared to SCD caregivers. Our study aimed to compare the QoL between caregivers of children and adolescents with SCD and HIV and explore factors associated with this QoL in Cameroon. We conducted a hospital-based cross-sectional analytic study at Douala Laquintinie Hospital from February to May 2023. A questionnaire was administered to caregivers of paediatric patients (≤18 years) with SCD and HIV. The Pediatrics Quality of Life-Family Impact Module (PedsQL FIM), the 7-item Generalized Anxiety Disorder (GAD-7), and the 9-item Patient Health Question (PHQ-9) tools were used as measures of quality of life, anxiety, and depression, respectively. Multivariable linear regression was used to determine factors associated with quality of life. A significance level was set at p < 0.05. We included 199 caregivers: SCD = 104 and HIV = 95. The mean age of caregivers in our sample was 40.47 ± 10.18 years. Caregivers of paediatric patients with HIV had a better mean quality of life than SCD (93.01 ± 7.35SD versus 64.86 ± 9.20SD, p < 0.001). PHQ-9 score (B = -1.52, 95% CI = [-2.08; -0.96], p=<0.001), GAD-7 score (B = -1.46, 95% CI = [-2.09; -0.83], p=<0.001), spending less than 75 000 FCFA on medications monthly (B = 12.13, 95% CI = [5.73; 18.94], p=<0.001), and being a SCD caregiver (B = -11.62, 95% CI = [-18.46; -4.78], p=0.001) were factors independently associated with quality of life on multivariable analysis. Quality of life is lower in caregivers of children and adolescents with SCD than with HIV. Preventing depression and anxiety as well as advocating for the subsidization of medications through a national SCD program may improve quality of life in SCD caregivers.

Iron supplementation and paediatric HIV disease progression: a cohort study among children receiving routine HIV care in Dar es Salaam, Tanzania.

Anaemia is common among HIV-infected children and iron supplementation is prescribed routinely for the prevention and management of anaemia among children. Limited evidence suggests iron supplementation may have adverse effects among HIV-infected populations. We aimed to estimate the effect of iron supplement use on mortality, disease progression and haematological outcomes among HIV-infected children in Dar es Salaam, Tanzania. A prospective cohort study was conducted among HIV-infected children (aged 0-14 years) receiving antiretroviral treatment or supportive care between October 2004 and September 2014. Clinical data were recorded on morbidity and vital status, haematological status and prescriptions at each clinical visit. Cox proportional hazards models adjusted for time-varying covariates were used to estimate the association of time-varying iron supplementation on the hazard rate of mortality, HIV disease stage progression, tuberculosis incidence and anaemia and microcytosis persistence. In all, 4229 children were observed during 149 260 clinic visits for a mean follow-up of 2.9 years. After adjustment for time-varying clinical covariates, time-varying iron supplementation was associated with a 2.87 times higher hazard rate of mortality (95% CI: 1.70, 4.87) and a 1.48 times higher hazard rate of HIV disease stage progression (95% CI: 1.10, 1.98). Iron supplementation was also associated with a lower rate of anaemia persistence (HR = 0.47; 95% CI: 0.37, 0.61). No differences in the association between iron supplementation and clinical outcomes were observed by antiretroviral therapy or anaemia status. Iron supplementation may increase the risk of HIV disease stage progression and mortality among HIV-infected children, while reducing the risk of anaemia.

Trends of the HIV/AIDS Phenomenon Dynamics in Romania from 2017-2027

HIV infection remains of major public health importance in all world and in Romania. In Romania there are a large number of long-term survivors coming from the 1987-1990 generation, the circumstances are due to the fact that an increased number of HIV-infected persons receive a specific therapy. The study was conducted using sociological analysis methods such as comparative analysis, statistical analysis, and with the help of the method of regression analysis, to capture the dynamics of the HIV / AIDS phenomenon in Romania, as well as forecasting the dynamics of the phenomenon over the next decade. This longitudinal analysis of the statistical data provided by the Matei Bals Institute of Romania during the period 2004-2016, shows a progressive increase 1.4 times higher in 2016 compared to 2004, the prediction of the extension of the HIV / AIDS phenomenon for the period 2017-2027, in Romania being almost constant. Regarding the prognosis of the number of persons affected by HIV / AIDS in Romania, for the next 10 years an upward dynamic is predicted with an increasing annual rate of 506 new persons taken into evidence. As the prediction function shows, the trend the access to treatment is increasing for the next decade. After 2006 in Romania, the deaths dynamics is an exponential decreasing one, keeping the same rate of decrease, until 2015. The HIV/AIDS pandemic has changed considerably in the past 27 years. AIDS incidence and mortality in industrialised countries have fallen, and paediatric HIV disease has almost been eliminated as a public health issue, largely through antiretroviral drugs.

Comparing the Diagnostics Accuracy of CD4+ T-Lymphocyte Count and Percent as a Surrogate Markers of Pediatric HIV Disease.

The percentage CD4+ T-lymphocytes is used to monitor pediatric HIV disease. However, in resource-limited settings, enumerating the percentage of CD4+ T-lymphocytes is hampered by the lack of laboratory infrastructure and trained technicians. In this paper, we investigated the performances of the percentage and absolute CD4+ T-lymphocytes as markers of pediatric HIV disease progression using data from HIV-infected children enrolled through the Yale Prospective Longitudinal Pediatric Cohort study. A Lehmann family of Receiver Operating Characteristic (ROC) curves were used to estimate and compare the performance of the two biomarkers in monitoring pediatric HIV disease progression. The area under the ROC (AUC) curve and its empirical estimator have previously been used to assess the performance of biomarkers for a cross-sectional data. However, there is a paucity of literature on the AUC for correlated longitudinal biomarkers. Previous works on the estimation and inference of the AUC for longitudinal biomarkers have largely focused on independent biomarkers or failed to consider the effect of covariates. The Lehmann approach allowed us to estimate the AUC of the aforementioned correlated longitudinal biomarkers as functions of explanatory variables. We found that the overall performance of the two biomarkers was comparable. The area under the ROC curves for CD4+ T cell count and percentage were 0.681 [SE = 0.029; 95% CI: 0.624-0.737] and 0.678 [SE = 0.024; 95% CI:0.630-0.725], respectively. Our results suggest that absolute CD4+ T-lymphocyte counts could be used as a proxy for percentage of CD4+ T-lymphocytes in monitoring pediatric HIV in resource-limited settings.

Challenges and Opportunities in the Development of HIV Medications in Pediatric Patients.

Successful management of pediatric HIV disease requires high therapeutic efficacy and adherence, which can be achieved by providing affordable, easy to store, and palatable antiretrovirals. Current challenges in pediatric antiretroviral drug development include poor palatability, large pill size, limited oral liquid formulations, and few incentives for development by drug manufacturers as the number of children with HIV continues to decline due to successful worldwide preventive interventions and improved access to antiretrovirals. This article summarizes the various challenges and opportunities with current pediatric antiretrovirals, recent and ongoing trials, new formulations, and suggestions that may expedite and provide incentives for the development of suitable pediatric formulations.

Oral Manifestations of HIV

Oral manifestations of HIV are common and have been important in identification of patients harboring the HIV virus and in predicting the decline in their immune system. Careful history taking and detailed examination of the patient’s oral cavity are important parts of the physical examination. Early recognition, diagnosis, and treatment of HIV-associated oral lesions may reduce morbidity. Orofacial manifestations are among the earliest and most common clinical signs of pediatric HIV disease too. Early diagnosis of perinatally exposed infants and children is especially important because the inter¬vals between infection, development of AIDS, and death are compressed in pediatric patients. Early diagnosis allows prompt institu¬tion of both multi-drug therapy, which appears to be most effective when instituted early, and prophylactic therapy to fore¬stall life-threatening opportunistic infections. The present paper discusses in detail the oral manifestations of HIV and their diagnostic criteria in adults as well as in pediatric patients.

The Effect of Early Initiation of Antiretroviral Treatment in Infants on Pediatric AIDS Mortality in South Africa

Guidelines for treatment of pediatric HIV have recently changed to recommend that all infants who are identified as HIV-infected should start antiretroviral treatment (ART) immediately, regardless of their immunologic or clinical status. This study aims to assess the likely impact of this change in guideline in South Africa. A mathematical model was developed to simulate mother-to-child transmission of HIV, disease progression, and death of HIV-infected children <15 years of age. The model is calibrated to South African data sources, including prevention of mother-to-child transmission program coverage data, pre-ART survival data, ART program statistics, and pediatric HIV prevalence studies. Relative to what would be expected in the absence of early ART initiation, the number of infant AIDS deaths over the 2010-2025 period is expected to drop by 23.6% (95% confidence interval [CI]: 22.5-24.5%) at current levels of polymerase chain reaction (PCR) diagnosis, and by 34.2% (95% CI: 32.7-35.6%) if PCR diagnosis increases to 80% of perinatally infected infants at 2 months. However, the pediatric HIV disease burden has shifted toward older children in recent years. The effect of early ART on total pediatric AIDS mortality during the 2010-2025 period is therefore modest: a 9.8% reduction (95% CI: 7.9-12.6%) at current levels of PCR diagnosis, and a 14.2% reduction (95% CI: 11.4-18.2%) if PCR coverage increases to 80% of perinatally infected infants. The changes in ART guidelines for infants will have a significant impact on pediatric AIDS mortality at young ages, but further efforts are required to reduce the substantial growing AIDS mortality in older children.

Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study

Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clinical variables. In a cross-sectional analysis, children aged 7-16 y in the Pediatric HIV/AIDS Cohort Study underwent regionalized measurements of body fat via anthropometric methods and dual-energy X-ray absorptiometry. Multiple linear regression was used to evaluate body fat by HIV, with adjustment for age, Tanner stage, race, sex, and correlates of body fat in HIV-infected children. Percentage total body fat was compared with NHANES data. Males accounted for 47% of the 369 HIV-infected and 51% of the 176 HEU children. Compared with HEU children, HIV-infected children were older, were more frequently non-Hispanic black, more frequently had Tanner stage ≥3, and had lower mean height (-0.32 compared with 0.29), weight (0.13 compared with 0.70), and BMI (0.33 compared with 0.63) z scores. On average, HIV-infected children had a 5% lower percentage total body fat (TotF), a 2.8% lower percentage extremity fat (EF), a 1.4% higher percentage trunk fat (TF), and a 10% higher trunk-to-extremity fat ratio (TEFR) than did the HEU children and a lower TotF compared with NHANES data. Stavudine use was associated with lower EF and higher TF and TEFR. Non-nucleotide reverse transcriptase inhibitor use was associated with higher TotF and EF and lower TEFR. Although BMI and total body fat were significantly lower in the HIV-infected children than in the HEU children, body fat distribution in the HIV-infected children followed a pattern associated with cardiovascular disease risk and possibly related to specific antiretroviral drugs.

Antiretroviral Drugs in Pediatric HIV-Infected Patients

Antiretroviral (ARV) therapy has been shown to achieve high therapeutic efficacy in treating pediatric HIV disease. The delivery of affordable, child friendly, and easy to store and administer ARV drugs is key to the successful management of HIV in children. In recent years, significant progress has been made in scaling up the access to pediatric ARV therapy among children worldwide. Despite the improved ARV drug access, multiple challenges remain concerning palatability and efficient delivery of ARV drugs to children from infancy into adolescence. Data are limited regarding developmental changes in pharmacokinetics of individual ARV drugs, and pediatric and adult fixed-dose combinations. This review provides a practical discussion regarding the pharmacokinetics of ARV agents in pediatric HIV-infected patients, as well as the practical challenges of currently available formulations, such as palatability of liquid formulations, challenges of crushing tablets, and using adult and pediatric fixed-dose combinations.

Early Mortality and Loss to Follow-up in HIV-Infected Children Starting Antiretroviral Therapy in Southern Africa

Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.

Relationships between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected youth

To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease. A cross-sectional design within a prospective, 15-site cohort study conducted in the United States. Nine vascular biomarkers were examined in 89 HIV-infected children: soluble P-selectin/sCD62P, fibrinogen, adiponectin, monocyte chemoattractant protein-1/CCL-2, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1/sCD106, sE-selectin/sCD62E, and soluble intercellular adhesion molecule-1/sCD54. The Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) was administered yielding indices for verbal comprehension, perceptual reasoning, working memory and processing speed, and overall composite Full-Scale IQ score. Linear regression models were used to evaluate neurodevelopmental status (measured by WISC-IV scores) as a function of each biomarker while adjusting for demographics, disease severity, and receipt of HAART. Biomarker levels were evaluated in quartiles to evaluate trends in WISC-IV responses. Among the 89 HIV-infected children (median age = 12 years), 56% were girls, 71% black, 16% Hispanic, and 43% had yearly household income below US $20,000. Log (soluble P-selectin) was significantly correlated with all WISC-IV scores; adjusted slopes showed 6-11-point average decrease in scores for each one log unit increase in soluble P-selectin. Final linear regression models for log (fibrinogen) adjusted for sociodemographic and disease characteristics also indicated a negative correlation with all WISC-IV scores (13-30-point decrease for each one log unit increase in fibrinogen); these decreases were significant in the verbal comprehension, perceptual reasoning, and Full-Scale IQ scores. Proinflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally acquired HIV disease.

The Contribution of Family Planning towards the Prevention of Vertical HIV Transmission in Uganda

BackgroundUganda has one of the highest total fertility rates (TFR) worldwide. We compared the effects of antiretroviral (ARV) prophylaxis for the prevention of mother-to-child HIV transmission (PMTCT) to that of existing family planning (FP) use and estimated the burden of pediatric HIV disease due to unwanted fertility.Methodology/Principal FindingsUsing the demographic software Spectrum, a baseline mathematical projection to estimate the current pediatric HIV burden in Uganda was compared to three hypothetical projections: 1) without ARV-PMTCT (to estimate the effect of ARV-PMTCT), 2) without contraception (effect of existing FP use), 3) without unwanted fertility (effect of unmet FP needs). Key input parameters included HIV prevalence, ARV-PMTCT uptake, MTCT probabilities, and TFR. We estimate that in 2007, an estimated 25,000 vertical infections and 17,000 pediatric AIDS deaths occurred (baseline projection). Existing ARV-PMTCT likely averted 8.1% of infections and 8.5% of deaths. FP use likely averted 19.7% of infections and 13.1% of deaths. Unwanted fertility accounted for 21.3% of infections and 13.4% of deaths. During 2008–2012, an estimated 131,000 vertical infections and 71,000 pediatric AIDS deaths will occur. The projected scale up of ARV-PMTCT (from 39%–57%) may avert 18.1% of infections and 24.5% of deaths. Projected FP use may avert 21.6% of infections and 18.5% of deaths. Unwanted fertility will account for 24.5% of infections and 19.8% of deaths.ConclusionsExisting FP use contributes as much or more than ARV-PMTCT in mitigating pediatric HIV in Uganda. Expanding FP services can substantially contribute towards PMTCT.

Chest radiographic pulmonary changes reflecting extrapulmonary involvement in paediatric HIV disease

Respiratory infections are the commonest cause of pulmonary change on chest radiographs of HIV-infected children. However, HIV-related neurological, oropharyngeal, oesophageal, cardiac and haematological abnormalities may also manifest with pulmonary changes and must be considered in the interpretation of the chest radiograph in HIV-infected children.

Absolute CD4+ T-Lymphocyte Count as a Surrogate Marker of Pediatric Human Immunodeficiency Virus Disease Progression

Traditionally in pediatric HIV, the CD4+ T-lymphocyte percent is used to monitor disease progression because of the variability in absolute CD4+ T-lymphocyte numbers. Because of the high cost of equipment, sophisticated and delicate technology, most laboratories in resource-limited settings use simple protocols that enumerate only the absolute CD4+ T-lymphocyte counts. We assessed the use of absolute CD4+ T-lymphocyte count as a surrogate marker of pediatric HIV disease progression. We analyzed the CD4+ T-lymphocytes and HIV viral load over a 10-year period (1996-2006) of 97 HIV-infected children enrolled in the Yale Prospective Longitudinal Pediatric HIV Cohort using generalized linear mixed models. Both CD4+ T-lymphocytes and HIV viral load were assessed at baseline and every 2-3 months. The modeling approach used in this study allows the intercept and the rate at which outcome variables change over time to vary across participants. We determined that absolute CD4+ T-lymphocytes count was just as reliable at monitoring pediatric HIV as CD4+ T-lymphocyte percentage. Antiretroviral treatment, regardless of the regimen used, was associated with higher CD+ T-lymphocytes count (P < 0.01). Race was significantly associated with CD4+ T-lymphocytes counts (with lower values for blacks compared with nonblacks; P < 0.01). The presence of other infections was associated with lower CD4+ T-lymphocyte count (P = 0.01) and higher viral load (P < 0.01), respectively. In situations where determination of CD4+ T-lymphocyte percentages is not readily available, the absolute count may provide an affordable and accessible laboratory surrogate marker of HIV disease progression in children.

Slow progression of paediatric HIV disease: Selective adaptation or a chance phenomenon?

Background: Disease progression in human immunodeficiency virus/Acquired immunodeficiency syndrome (HIV/AIDS) is affected by several factors both external and internal to the human hosts. In the European Caucasian populations, the chemokine-cell receptor variant CCR5 \Delta 32 is a the genetic determinant of HIV disease progression that is believed to have been selected for in the general population by exposure to antigens closely interlinked to HIV like Yersinia pestis or small pox virus. Among African populations, it is possible that this selection will be induced by HIV over time. Aim: To present two cases of mother-to-child transmitted HIV highlighting the possible increasing prevalence of slow disease progression. Methods: Clinical case reports of slow progression of pediatric HIV Results: Both patients were female, had lost one parent >10yrs earlier but had the other surviving parent exhibiting slow HIV disease progression. We question the possible inheritance of the genetic factors associated with slow disease progression in a recessive X-linked Mendellian pattern and the role of the high prevalence of HIV within the sub-Saharan setting as the selective pressure favoring the establishment of the currently known immunologic and genetic factors influencing HIV diseases progression. Conclusion: A more in-depth immunologic and genetic approach is called for to further examine the baseline prevalence and possibility of adaptive selection for immunogenetic protectors of HIV disease progression within the sub-Saharan setting. Keywords : Paediatric HIV, Slow progression, Selective adaptation, Chance phenomenon Port Harcourt Medical Journal Vol. 2 (1) 2007: pp. 83-87

Care and Treatment of HIV-Infected Children in Africa

More than 90% of pediatric HIV infection occurs in sub-Saharan Africa and 75% of these children currently die before their fifth birthday. Most HIV-infected children in Africa rely on district hospitals for HIV treatment, but insufficient attention has been paid to improving HIV/AIDS care at this level. Considerable confusion exists about optimal use of combination antiretroviral treatment, prophylaxis for opportunistic infections and other rational healthcare interventions that can greatly improve the quality of life for these children. A simple and inexpensive infant HIV diagnostic assay and alternative laboratory markers of pediatric HIV disease progression would be highly beneficial. Routine anthropometric and neurodevelopmental assessments could help guide initiation and monitoring of antiretroviral therapy. Even in the absence of antiretroviral therapy, interventions such as immunizations, provision of micronutrients and nutrition counseling, prevention and treatment of opportunistic as well as endemic infections (such as helminths and malaria) can substantially reduce pediatric HIV-related morbidity and mortality. The need for pain relief, palliative care, counseling and emotional support is often underestimated. Surmounting the sense of hopelessness by providing district healthcare workers with training in basic pediatric HIV/AIDS care is an urgent priority.

Health-Related Quality of Life of HIV-Infected Children on Complex Antiretroviral Therapy at Home

The study describes quality of life as perceived by parents and measured by the Child Health Questionnaire (CHQ-28) for a convenience sample of 33 HIV-infected children age 5 to 18 years cared for at home on complex antiretroviral drug regimens. When compared with normative data on healthy U.S. children, parent reports for the HIV-infected children did not differ significantly on the following CHQ concepts: role/social related to emotional, behavioral or physical problems; bodily pain; behavior; mental health; self-esteem; impact on parental time; family activities; and family cohesion. Parents perceived their children to be functioning at a level significantly lower than the norm in general health (t -6.47, p = .000), physical functioning (t -2.37, p = .024), and physical summary (t -3.80, p = .001). Parental impact-emotional was impressively higher than the norm (t -3.74, p = .001). Differences were independent of gender, primary language, ethnicity, and Centers for Disease Control and Prevention clinical classifications for pediatric HIV disease.

Achieving Adherence to Antiretroviral Medications for Pediatric HIV Disease Using an Empirically Supported Treatment

Adherence to antiretroviral medication regimens among human immunodeficiency virus positive-children is influenced by a number of psychosocial factors including characteristics of the child, the caregiver, the medical team, and the medications. To address these factors requires treatment approaches that are flexible and comprehensive. One such treatment approach is multisystemic therapy (MST), an empirically supported intensive home-based treatment approach that has been proven effective with other chronic pediatric conditions. This case report describes the use of MST with a poorly adherent, perinatally infected adolescent.

Rapid HIV screening for women in labor

Women now comprise approximately half of all HIV-infected individuals and the epidemic of pediatric HIV disease continues unabated in the developing world. The issue of mother-to-child transmission has been a major concern for public health officials since the early years of this epidemic. Not uncommonly, the first opportunity to ascertain the HIV status is when a woman presents to a hospital in labor. Rapid HIV tests can provide fast results, allowing time for the provider to offer antiretroviral therapy. Several effective antiretroviral regimens are now available for the intrapartum patient whose rapid HIV test comes back as positive. Antiretroviral therapy should be initiated as soon as possible after a positive rapid HIV test result and prior to standard confirmatory testing. This article summarizes the epidemiology of HIV and focuses on testing policies, technologies for rapid screening for HIV infection and antiretroviral regimens that can reduce the risk of perinatal transmission from the intrapartum patient whose rapid HIV test comes back positive.

In vitro measurement of cytotoxic T cell activity does not predict clinical progression in paediatric HIV disease—two case studies

SUMMARY Cytotoxic T cells are believed to be an important immune response in HIV infection, both in the initial response to viraemia, and in controlling HIV replication and maintaining clinical stability. We report here the detailed findings in two vertically infected children, from the Edinburgh perinatal cohort. Both were clinically stable for the first 7 years of life. One had vigorous HIV-specific cytotoxic T lymphocyte (CTL) responses, and non-lytic suppression, measured in vitro, while the second had no CTL activity against HIV. Despite her HIV-specific immunity, the first child had a declining CD4 count, and a high and fluctuating viral load, whereas the second child maintained a stable CD4 count, a low viral load and had a virus which could not be cultured in peripheral blood mononuclear cells (PBMC) in vitro. The first child subsequently progressed to AIDS and has now died, while the second remains clinically well. More detailed investigations showed the clinically stable child to be heterozygous for the CCR5 receptor, and to be HLA-B49—both of which markers have been associated with slow HIV disease progression. These findings question the role of CTL in maintaining stable HIV disease, and stress the need for immunological investigations to be considered in the light of the genetic make-up of the patient. They may also reflect a different immunopathogenesis of HIV disease in children compared with adults.