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.

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.

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.

Zidovudine use to reduce perinatal HIV type 1 transmission in an urban medical center.

OBJECTIVE: To evaluate whether zidovudine treatment was accepted and used by pregnant women subsequent to the release of the results of a multicenter, randomized, placebo-controlled trial (AIDS Clinical Trial Group [ACTG] Protocol 076) that showed that zidovudine significantly reduced maternal-infant human immunodeficiency virus (HIV) type 1 transmission. DESIGN: Prospective study. SETTING: A community hospital with an integrated, multidisciplinary HIV-dedicated program located in an impoverished, HIV-endemic urban setting. PARTICIPANTS: All HIV-infected pregnant women identified after the release of the ACTG 076 results who were offered zidovudine therapy to reduce maternal-infant transmission. RESULTS: Only 49 of the 125 HIV-infected pregnant women delivering at our site during this study period were identified prenatally. Perinatal zidovudine therapy was chosen by 37 (75%) of 49 women. Women refusing zidovudine were more likely to report injection drug use as their HIV risk factor and to continue to use drugs during their pregnancy. Of women choosing zidovudine and delivering, 24 of 36 received all components of their elected therapy. The intrapartum dose was missed by 12 women, 4 of whom also missed their prescribed prenatal oral therapy. Lack of adherence to chosen therapy was associated with continued cocaine use during pregnancy. CONCLUSIONS: Zidovudine therapy to interrupt vertical transmission of HIV was not widely used by these HIV-infected pregnant women. Further studies evaluating factors affecting the acceptance and use of recently published public health recommendations are needed.

Virologic, immunologic, and clinical evaluation of human immunodeficiency virus antibody status of symptom-free children born to infected mothers.

STUDY OBJECTIVE: To determine the prevalence of infection by the human immunodeficiency virus (HIV) in a population of symptom-free children who were born to HIV-infected mothers and who subsequently underwent seroreversion from an HIV antibody-positive to an HIV antibody-negative status. DESIGN: Cohort. SETTING: Pediatric HIV program in a community setting. PATIENTS: We used HIV DNA polymerase chain reaction (PCR) and coculture to detect the presence or absence of HIV in peripheral blood mononuclear cells of 134 children aged 6 to 53 months. All children had HIV antibody at birth and underwent a subsequent seroreversion to antibody-negative status. RESULTS: In 134 children with HIV antibody-negative status, 219 of 220 culture results and 242 of 247 HIV-1 DNA PCR assay results were negative. Six positive laboratory results were obtained for six different children, each of whom had negative results on multiple assays. For HIV-infected children, 56 of 62 cultures and 99 of 104 PCR evaluations showed positive results. There was no clinical or laboratory evidence of HIV infection in the group with HIV antibody-negative status. CONCLUSION: We were unable to find evidence of latent HIV type 1 infection in this cohort of symptom-free children who underwent seroreversion to HIV antibody-negative status. The loss of maternal HIV antibody in these children indicates the absence of HIV infection. False-positive PCR and culture results occurred sporadically, indicating that repeated analysis of HIV seropositivity in infants and children is necessary.

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.

Effects of congenital HIV infection on neurodevelopmental status of babies in foster care.

High rates of neurological complications related to congenital HIV infection have been reported, but often it has been difficult to delineate those clinical impairments specifically related to viral infection of the developing nervous system. The present study attempted to hold causative environmental factors constant by comparing the neurodevelopmental and growth status of two matched control groups of infants in foster care, one HIV seronegative and one seropositive. All were over the age of 15 months and had been born to seropositive mothers. The seropositive group showed significantly more neurological involvement than the seronegative group, and a different pattern of cognitive deficits. There were no significant differences in growth measures between the two groups. Babies born to HIV seropositive mothers were generally at high risk for developmental impairments.

Fetal AIDS syndrome score. Correlation between severity of dysmorphism and age at diagnosis of immunodeficiency.

To objectively evaluate the fetal acquired immunodeficiency syndrome, we have developed a scoring system based on the presence of the characteristic features that we have previously reported. Using this scoring system, 37 children seropositive for the human immunodeficiency virus were classified into three groups: dysmorphologically severely affected (12 children); moderately affected (15 children); and mildly affected (ten children). There was a statistically significant correlation between the severity of the dysmorphic features and both the presence of opportunistic infections within the first year of life and the age at onset of symptoms associated with immune dysfunction, with the more severely stigmatized children manifesting symptoms at a younger age. There was no correlation, however, between severity of the dysmorphic features and presence of opportunistic infections at the time of our examination. We conclude that this scoring system may be useful in presymptomatic identification of severely dysmorphic human immunodeficiency virus-infected infants.

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.