Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.

Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.

Construct Validity Supports Use of a Novel, Tablet-Based Neurocognitive Assessment for Adolescents and Young Adults Affected by Perinatal HIV from Vulnerable Communities in the United States.

Construct validity of novel tablet-based neurocognitive tests (in the NeuroScreen app) measuring processing speed, working memory, and executive functioning in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU) was examined. Sixty-two AYA (33 PHIV, 29 PHEU) were recruited from an ongoing longitudinal study (CASAH) in New York City. Medium to large and statistically significant correlations were found between NeuroScreen and gold standard, paper-and-pencil tests of processing speed, working memory, and executive functioning. Results provide partial support for NeuroScreen as an alternative to cumbersome paper-and-pencil tests for assessing neurocognition among HIV-affected AYA.

Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood.

There are an estimated 2.1 million youth less than 15 years of age living with HIV globally (the majority perinatally HIV-infected [PHIV]) and millions more perinatally HIV-exposed uninfected (PHEU) youth who are expected to survive through adolescence and into adulthood. Transitioning from adolescence to young adulthood requires adaptation to more demanding social interactions, academic pressures, and individual responsibilities which place distinct demands on neurocognitive functions. This study examined longitudinal trajectories of neurocognitive test performance in the domains of processing speed (PS), working memory (WM), and executive functioning (EF) among PHIV and demographically similar PHEU from adolescence through young adulthood. Data for this paper come from four time points, spanning approximately 10 years, within the Child and Adolescent Self-Awareness and Health Study (CASAH). Youth age ranged from 15 to 29 years. Longitudinal linear mixed effect models were computed for each test. Few differences in performance were found on tests of EF and WM between PHIV and PHEU youth as they aged, though PHEU youth showed significantly better PS as they aged than PHIV youth. Future research is needed to understand these vulnerable youth's neurocognitive trajectories as a function of HIV infection and -exposure, biological functions and psychosocial stressors.

HIV-1 drug resistance prevalence, drug susceptibility and variant characterization in the Jacobi Medical Center paediatric cohort, Bronx, NY, USA.

OBJECTIVES: With the advent of combined antiretroviral therapy (cART), perinatally HIV-infected children are surviving into adolescence and beyond. However, drug resistance mutations (DRMs) compromise viral control, affecting the long-term effectiveness of ART. The aims of this study were to detect and identify DRMs in a HIV-1 infected paediatric cohort. METHODS: Paired plasma and dried blood spots (DBSs) specimens were obtained from HIV-1 perinatally infected patients attending the Jacobi Medical Center, New York, USA. Clinical, virological and immunological data for these patients were analysed. HIV-1 pol sequences were generated from samples to identify DRMs according to the International AIDS Society (IAS) 2011 list. RESULTS: Forty-seven perinatally infected patients were selected, with a median age of 17.7 years, of whom 97.4% were carrying subtype B. They had a mean viral load of 3143 HIV-1 RNA copies/mL and a mean CD4 count of 486 cells/µL at the time of sampling. Nineteen patients (40.4%) had achieved undetectable viraemia (< 50 copies/mL) and 40.5% had a CD4 count of > 500 cells/µL. Most of the patients (97.9%) had received cART, including protease inhibitor (PI)-based regimens in 59.6% of cases. The DRM prevalence was 54.1, 27.6 and 27.0% for nucleoside reverse transcriptase inhibitors (NRTIs), PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Almost two-thirds (64.9%) of the patients harboured DRMs to at least one drug class and 5.4% were triple resistant. The mean nucleotide similarity between plasma and DBS sequences was 97.9%. Identical DRM profiles were present in 60% of plasma-DBS paired sequences. A total of 30 DRMs were detected in plasma and 26 in DBSs, with 23 present in both. CONCLUSIONS: Although more perinatally HIV-1-infected children are reaching adulthood as a result of advances in cART, our study cohort presented a high prevalence of resistant viruses, especially viruses resistant to NRTIs. DBS specimens can be used for DRM detection.

A 12-month study of the effects of oral zidovudine on neurodevelopmental functioning in a cohort of vertically HIV-infected inner-city children.

OBJECTIVE: To examine the effects of oral zidovudine on the neurodevelopmental functioning of HIV-infected children. METHODS: Oral zidovudine was administered to 54 symptomatic children with vertically transmitted HIV infection (Centers for Disease Control and Prevention class P2). All children were recruited from an inner-city pediatric HIV/AIDS outpatient clinic and ranged in age from 2 months to 12 years and 11 months (mean age, 3 years) at entry. Neurodevelopmental functioning, height and weight, and lymphocyte subpopulation data were ascertained for all the children pretherapy, and 6 and 12 months post-therapy initiation. RESULTS: Analysis of the 6- and 12-month post-initiation drug data found no significant change in neurodevelopmental functioning. Height and weight percentiles remained the same or improved in the majority of children. CD4+ cell counts declined over the treatment period with CD4+ counts < 500 x 10(6)/l observed in 15% of the children pre-therapy, and 33% after 1 year. CONCLUSION: In contrast with previously published data, the present study observed no improvement in neurodevelopmental functioning in HIV-infected children treated with oral zidovudine.

Measles antibody in vaccinated human immunodeficiency virus type 1-infected children.

OBJECTIVES: The goals of this study were to evaluate the proportion of previously vaccinated human immunodeficiency virus (HIV) type 1-infected children with detectable postvaccination measles antibody; to assess risk factors for vaccine failure; and to evaluate the response to reimmunization. METHODS: A total of 81 perinatally HIV-infected children receiving medical care in the Bronx, New York who had previously received measles vaccine were enrolled. The Centers for Disease Control and Prevention (CDC) HIV class, lymphocyte subsets, and measles antibody were determined upon enrollment. Additional data abstracted from medical records included dates and number of prior measles vaccinations and CDC HIV class at the time of vaccination. Measles antibody was determined by microneutralization enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at time of study was 42 months (range, 9 to 168 months). Overall, 58 (72%) subjects had detectable measles antibody (microneutralization ELISA titer > 1:5). Children studied within 1 year of vaccination were more likely to have detectable measles antibody than children evaluated more than 1 year after vaccination (83% vs 52%, P < .01). The proportion of children with detectable measles antibody was higher among children with no or moderate immunosuppression compared to those with severe immunosuppression when immune status was based on CD4%. Children vaccinated at 6 to 11 months of age appeared to have a higher proportion of detectable measles antibody than those who received a first measles vaccination after age 1. Only 1 (14%) of 7 previously vaccinated children who were seronegative or had very low titers experienced a four-fold rise in measles antibody when reimmunized. CONCLUSION: These results support current recommendations to vaccinate HIV-infected children against measles. The proportion of children with detectable measles antibody among vaccinated HIV-infected children is considerably lower than in vaccinated healthy children. HIV-infected children may respond better to measles vaccine when it is administered before the first birthday. From our limited data it appears that reimmunization of previously vaccinated HIV-infected children with moderate to severe immunosuppression does not result in an antibody recall response.

Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team.

One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.

Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia in infants with human immunodeficiency virus infection.

Aerosolized pentamidine is widely used in adult patients with human immunodeficiency virus as both prophylaxis and therapy for Pneumocystis carinii pneumonia. The aim of this study was to evaluate the safety of a monthly regimen of aerosolized pentamidine in human immunodeficiency virus-infected infants. Seven human immunodeficiency virus-infected infants, ages 3.5 to 11 months, were given a total of 45 monthly treatments of aerosolized pentamidine. The infant's dose of pentamidine was based on an adult dosage of 300 to 600 mg/month, adjusted for minute ventilation and weight. There were no discernible clinical side effects in 62% (28 of 45) of the treatments. Observed toxicity included mild to moderate coughing, mild wheeze and transient arterial desaturation as measured by pulse oximetry. Pulmonary function data revealed an increased tidal volume (P < 0.005) and an increased pulmonary resistance (P < 0.02) post-pentamidine treatment. Urinary pentamidine concentrations were obtained and pentamidine was detected in all tested samples suggesting pulmonary deposition and systemic absorption. In conclusion aerosolized pentamidine appears to be a relatively safe, well-tolerated treatment in infants, with side effects similar to those seen in adults.

Human immunodeficiency virus seropositivity in critically ill neonates in the south Bronx.

Cord blood was anonymously screened to determine the prevalence of human immunodeficiency virus (HIV) seropositivity in neonates admitted to the neonatal intensive care unit (NICU) at the Bronx Lebanon Hospital Center, located in the South Bronx. We speculated that factors leading to admission to the NICU such as low birth weight, prematurity and being small for gestational age would also be associated with an increased prevalence of HIV seropositivity. During the study period the prevalence of HIV seropositivity was 11.6% in the NICU population. There was no significant difference in maternal age, gravidity, race and sex in HIV-seropositive vs. HIV-seronegative newborns. There was a significantly increased incidence of maternal drug use (P less than 0.01), babies small for gestational age (P less than 0.005) and microcephaly (P less than 0.02) in seropositive vs. seronegative NICU babies. The results of this study suggest that the NICU population may comprise a significant number of infants of HIV-infected mothers.

Combination antiretroviral therapy in human immunodeficiency virus-infected pregnant women.

OBJECTIVE: To describe the safety, efficacy, and perinatal transmission rates of human immunodeficiency virus (HIV) with combination antiretroviral therapy in pregnancy. METHODS: Retrospective study of all HIV-infected pregnant women treated with combination antiretroviral therapy after September 1, 1996, and who delivered by September 1, 1998, at Bronx-Lebanon Hospital Center. RESULTS: Thirty women received combination therapy, 13 with protease inhibitor. Median baseline CD4 was 285 cells/mm3; 16 (53%) had AIDS, 20 (67%) were antiretroviral-experienced, and 11 (37%) were illicit substance users. Fourteen were receiving antiretroviral therapy (eight with protease inhibitor) during the first trimester. Combination therapy was prescribed for a median of 26 weeks during pregnancy. One third changed antiretroviral therapy, and nearly half (47%) were nonadherent. Twenty-four women had a successful viral load and/or CD4 response. The median (range) delivery gestation was 39 (32-42) weeks, and the median (range) birth weight was 2892 (1430-3863) g. Adverse outcomes included one stillbirth; one case of microcephaly; and five infants less than 2500 g, two of which were under 36 weeks' gestation. Median birth weight did not differ with maternal protease exposure. None of the 26 infants studied for at least 4 months had HIV infection. Associated maternal complications were four cases of pregnancy-induced hypertension, one of gestational diabetes, and one exacerbation of hepatitis C virus. CONCLUSION: Combination antiretroviral therapy in pregnancy was efficacious in reducing viral load, increasing CD4, and preventing vertical HIV transmission in women with advanced HIV disease, extensive antiretroviral experience, prior history of vertical transmission, and/or substance abuse. The findings are promising in this preliminary report that combination antiretroviral therapy may not be related to major infant toxicity, but further study is warranted.

Brain lactate and N-acetylaspartate in pediatric AIDS encephalopathy.

Two children with acquired immunodeficiency syndrome (AIDS) and progressive encephalopathy underwent MR spectroscopy before and after antiretroviral therapy. Initial MR spectroscopy of the basal ganglia region showed decreased N-acetylaspartate (NAA)/creatine (Cr) and a lactate peak. After therapy, there was improvement in NAA/Cr and an absence of the abnormal lactate peak. We suggest that decreased NAA/Cr in AIDS is reversible, that brain lactate might correlate with inflammation, and that MR spectroscopy can be useful in treatment trials.

Pediatric HIV infection.

Developments in the prevention and treatment of HIV infection in pregnant women and their children are encouraging. Perinatal ZDV therapy can reduce the maternal-infant transmission rate by two thirds in select populations. New therapies and the development of diagnostic assays to monitor HIV viral burden have renewed hope that, by aggressively controlling viremia, the progressive immunodeficiency can be delayed or even prevented. The general pediatric approach of preventing illnesses through aggressive vaccination and education policies must be actively incorporated into an approach to this epidemic. Success in controlling the pediatric HIV epidemic requires a concerted, coordinated effort by public policy makers, health care providers, basic science researchers, and those who are HIV-infected.

Disseminated gonorrhoea from a pharyngeal infection in a prepubertal child.

A young boy with disseminated gonorrhoea from the pharynx is presented. The clinical setting in which this may be seen is also discussed.

Human T-cell lymphotropic virus type III (HTLV-III) embryopathy. A new dysmorphic syndrome associated with intrauterine HTLV-III infection.

Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus type III (HTLV-III) were noted to have similar features including growth failure (75%), microcephaly (70%), and craniofacial abnormalities consisting of ocular hypertelorism (50%); prominent box-like appearance of the forehead (75%); flat nasal bridge (70%); mild upward or downward obliquity of the eyes (65%); long palpebral fissures with blue sclerae (60%); short nose with flattened columella and well-formed, triangular philtrum (65%); and patulous lips (60%). These features constitute a new and distinct dysmorphic syndrome, the HTLV-III embryopathy.