Ricardo Hugo Oliveira

Pregnancy outcome in women infected with HIV-1 receiving combination antiretroviral therapy before versus after conception

Objective: The potential adverse effects of antiretroviral drugs during pregnancy are discrepant and few studies, mostly from Europe, have provided information about pregnancy outcomes of those already on treatment at conception. The aim of this study was to investigate the impact of antiretrovirals (ARVs) on pregnancy outcome according to the timing of treatment initiation in a cohort of pregnant women from Brazil infected with HIV. Methods: A prospective cohort of 696 pregnant women followed up in one single centre between 1996 and 2006 was studied. Patients who had ARV treatment before pregnancy were compared with those treated after the first trimester. The outcomes evaluated were preterm delivery (PTD) (<37 weeks), severe PTD (<34 weeks), low birth weight (LBW) (<2500 g) and very LBW (<1500 g). Results: Patients who were using ARVs pre-conception had higher rates of LBW (33.3% vs 16.5%; p<0.001) and a similar trend for PTD (26.3% vs 17.7%; p = 0.09). Stratification by type of therapy (dual vs highly active antiretroviral therapy (HAART)) according to timing of initiation of ARVs showed that patients who use HAART pre-conception have a higher rate of PTD (20.2% vs 10.2%; p = 0.03) and LBW (24.2% vs 10.2%; p = 0.002). After adjusting for several factors, HAART used pre-conception was associated with an increased risk for PTD (AOR 5.0; 95% CI 1.5 to 17.0; p = 0.009) and LBW (OR 3.6; 95% CI 1.7 to 7.7; p = 0.001). Conclusions: We identified an increased risk for LBW and PTD in patients who had HAART prior to pregnancy.

Expression of APOBEC3G/3F and G-to-A hypermutation levels in HIV-1-infected children with different profiles of disease progression.

Objective Increasing evidence has accumulated showing the role of APOBEC3G (A3G) and 3F (A3F) in the control of HIV-1 replication and disease progression in humans. However, very few studies have been conducted in HIV-infected children. Here, we analyzed the levels of A3G and A3F expression and induced G-to-A hypermutation in a group of children with distinct profiles of disease progression. Methodology/Principal Findings Perinatally HIV-infected children were classified as progressors or long-term non-progressors according to criteria based on HIV viral load and CD4 T-cell counts over time. A group of uninfected control children were also enrolled in the study. PBMC proviral DNA was assessed for G-to-A hypermutation, whereas A3G and A3F mRNA were isolated and quantified through TaqMan® real-time PCR. No correlation was observed between disease progression and A3G/A3F expression or hypermutation levels. Although all children analyzed showed higher expression levels of A3G compared to A3F (an average fold of 5 times), a surprisingly high A3F-related hypermutation rate was evidenced in the cohort, irrespective of the childs disease progression profile. Conclusion Our results contribute to the current controversy as to whether HIV disease progression is related to A3G/A3F enzymatic activity. To our knowledge, this is the first study analyzing A3G/F expression in HIV-infected children, and it may pave the way to a better understanding of the host factors governing HIV disease in the pediatric setting.

Pregnancy in HIV vertically infected adolescents and young women: a new generation of HIV-exposed infants.

Background:Vertically infected individuals are reaching childbearing age and the new generation of HIV-exposed infants is coming to pediatric care. Methods:Chart review of pregnancies among HIV vertically infected adolescents and young women. Results:Fifteen pregnancies were reviewed. Girls had HIV diagnosis at median age 10.1 years (range 1.3–20). They started sexual life at median age 15 years (range 13–19); median age at pregnancy was 16.9 years (range 14–21.5); 36.4% had presented an AIDS-defining clinical event; have been followed for median 8.5 years (range 2.9–15.8) and had used median two antiretroviral regimens (range 0–7). Fourteen (93.3%) received antiretroviral drugs during pregnancy; median CD4 cell count during pregnancy was 394 (range 117–651) cells/μl and median viral load was 4800 copies/ml (range 50–100 000); 54% had undetectable viral load near delivery. All patients delivered by elective c-section. Median birth weight was 2650 g (range 2085–3595), median length was 47.3 cm (range 42–51) and median gestational age 38 weeks (range 37–39). All newborn received zidovudine for 6 weeks of life and none was breastfed. Fourteen (93%) infants were considered HIV-uninfected; one was lost to follow-up. Conclusions:This group of adolescents seems to have sexual behavior similar to that of HIV-uninfected. Since this is an experimented antiretroviral population, new drugs may be necessary for adequate viral suppression to avoid HIV mother-to-child transmission. Follow-up of this third generation of HIV-exposed infants needs to be addressed within HIV adolescent care.

Growth parameters in HIV-vertically-infected adolescents on antiretroviral therapy in Rio de Janeiro, Brazil.

Abstract Background: Growth failure in HIV-infected children is an important factor in either initiating or changing antiretroviral therapy (ART). This study assesses the impact of HIV infection on growth parameters of adolescents who acquired HIV vertically. Methods: This retrospective, longitudinal study involved adolescents aged 10–20 years with vertically-acquired HIV infection who were followed up in one of the three main referral centres for paediatric HIV/AIDS in Rio de Janeiro, Brazil. Length, weight and variables related to demographic, clinical and laboratory issues were analysed. Results: 108 subjects were enrolled. Median age was 12.7 years, median duration of follow-up was 97.2 months and 61 (56.5%) were female. The difference between the baseline and final weight Z-scores was −0.31 (p=0.02). Patients with final weight Z-scores ≤ −2 used more ART regimens (average 4.13) than those with Z-scores > −2 (average 2.90, p<0.01) and also had a lower final CD4+ cell percentage — average 19% vs 24% (p<0.01), respectively. The difference between baseline and final-height Z-scores was −0.27 (p<0.01). Several factors were associated with a final-height Z-score ≤ −2: clinical stage C during follow-up (RR 1.60, 95% CI 1.11–2.31), chronic diarrhoea during follow-up (RR 2.02, 95% CI 1.04–3.90), HAART use (RR 1.41, 95% CI 1.16–1.71), number of ART regimens (p<0.01) and final CD4+ cell percentage (p<0.01). In multivariate analysis, presentation in clinical stage C during follow-up was the only significant variable (OR 4.04, 95% CI 1.23–13.28). Conclusion: Even on HAART, HIV-infected adolescents have lower growth parameters than the normal population and this is associated with a worse prognosis.

Prevalence of oral hairy leukoplakia in 120 pediatric patients infected with HIV-1

Oral hairy leukoplakia (OHL) is an EBV (Epstein-Barr virus) opportunistic infection found in HIV-infected patients. It is an asymptomatic lesion that has an important prognostic value in AIDS. Differently from what takes place with HIV adult patients, OHL has been described in the literature as having a very small prevalence in pediatric patients. Therefore, the aim of this study was to investigate the prevalence of OHL in HIV pediatric patients using cytopathology. The sample consisted of 120 patients who were submitted to oral examination and had material scraped from both sides of their tongues. The diagnostic criterion was based on the identification of nuclear alterations. Clinical OHL was identified in two (1.67%) patients. The cytopathology revealed twenty (16.7%) cases of subclinical OHL. Our results show that in pediatric patients the prevalence of OHL may be larger than that described in the literature.

Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants.

Objective: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on the course of HIV‐1 infection in children by comparing the clinical outcome of infants born to HIV‐1‐seropositive mothers who did versus those who did not receive ZDV during pregnancy. Methods: Medical records of HIV‐1‐seropositive mothers and their infants were reviewed retrospectively. Participants were divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was rapid disease progression (RPD) in the infant, defined as occurrence of a category C disease or AIDS‐related death before 18 months of age. Results: HIV vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012), and prematurity was significantly associated with a higher risk of RPD (p = .027). Conclusions: The rate of RPD was significantly higher among perinatally infected infants born to HIV‐infected mothers treated with ZDV than among infected infants born to untreated mothers. The decreased proportion of infected infants with nonrapid disease progression in the former group might be related to the ability of ZDV to block intrapartum transmission preferentially and also to nonrapid disease progression resulting from intrapartum transmission.

Overview of genotypic and clinical profiles of human immunodeficiency virus type 1-infected children in Rio de Janeiro, Brazil

Although mother-to-child HIV transmission prevention has slowed down pediatric HIV infection in developed countries, large numbers of infants still become infected in developing nations. Data on pediatric HIV infection is however largely scarce. In this study, we have overviewed clinical, laboratory and genotypic data from a large cohort of HIV-infected infants regularly followed at two pediatric HIV outpatient clinics in Rio de Janeiro, Brazil. Children on antiretroviral therapy, as well as drug-naive, newly diagnosed infants were analyzed. Prevalence of drug resistance mutations, as well as immunological and virological responses to therapy were evaluated. Additionally, HIV-1 subtype frequencies and their distribution over the course of the epidemic were studied. We have found a high prevalence of mutations among ARV-experienced children, whereas mutations were absent in the drug-naive group. Despite the high levels of resistance among treated infants, an important improvement of their immunological status was observed. HIV-1 subtype distribution followed the trends of the adult population, with the appearance of non-B subtypes and recombinant forms after 1990. To our knowledge, this is the largest pediatric cohort ever analyzed in Brazil, and the data provided is of paramount importance to a better understanding of HIV/AIDS evolution in pediatric settings.

Alternative, age- and viral load-related routes of nelfinavir resistance in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy.

To assess prevalence of nelfinavir resistance mutations in children receiving highly active antiretroviral therapy, sequencing of protease gene from plasma of 53 human immunodeficiency virus-infected children was performed. The prevalence of L90M was similar to that of D30N. There was a significant correlation with a higher viral load and lower age and the occurrence of L90M. These findings suggest differential molecular age- and viral load-related routes for nelfinavir resistance.

Bioavailability of Once- and Twice-Daily Regimens of Didanosine in Human Immunodeficiency Virus-Infected Children

ABSTRACT The bioavailability of didanosine at 180 mg/m2 once daily was compared to that at 90 mg/m2 twice daily in 24 children with advanced human immunodeficiency virus infection. Children were studied at steady state using optimal sampling and prior pharmacokinetic parameter estimates. Relative bioavailability was 0.95 ± 0.49, supporting the potential clinical adequacy of once-daily dosing.

Progressive multifocal leukoencephalopathy in a child with acquired immunodeficiency syndrome (AIDS)

Progressive multifocal leukoencephalopathy is a rare viral-induced demyelinating disease associated to immunodeficiency. A 10-year-old boy with AIDS is reported, who developed subacute cerebellar signs and symptoms with multiple cranial nerve involvement and dementia. A computed tomography scan revealed a focal nonenhancing area of low attenuation in the cerebellum. On magnetic resonance imaging high signal lesions in T2 weighted sequences were shown. The biopsy of one of those lesions showed the typical histological findings of progressive multifocal leukoencephalopathy. It seems important to consider this diagnosis in children with AIDS who present with progressive neurological features.