Cervical cytological abnormalities and HPV infection in perinatally HIV-infected adolescents.

BACKGROUND: Behaviourally HIV-infected adolescent females are at higher risk for abnormal cervical cytology and HPV infection compared to those who are uninfected, but data on perinatally HIV-infected adolescent females are lacking. METHODS: Cervical cytology, HPV infection and E6/E7 mRNA were assessed in sexually active 12-24-year-old adolescent females: perinatally HIV-infected (group 1, n = 40), behaviourally HIV-infected (group 2, n = 10), and HIV-uninfected (group 3, n = 10). RESULTS: Median age was lower in group 1 (18 years) than in groups 2 (24 years) and 3 (20.5 years) (P < 0.001), and median time since sexual debut was shorter: 2 vs 5 vs 4 years (P < 0.001). More trial participants in group 1 than group 2 were on antiretrovirals (90% vs 70%; P <0.001). Abnormal cervical cytology (atypical squamous cells of undetermined significance and higher) was observed in 30% (group 1), 40% (group 2) and 30% (group 3) (P = 0.92), whereas high-risk HPV infection was observed in 45%, 45% and 40%, respectively (P = 1.00). Positive E6/E7 mRNA was found in 28% of group 1, but not in other groups. High-risk HPV infection predicted abnormal cytology in all groups [OR 6.77, 95% confidence interval (CI) 1.99-23.0; P = 0.001). Additionally, plasma HIV RNA ≥50 copies/mL (OR 13.3, 95% CI 1.16-153.06; P = 0.04) predicted abnormal cytology in HIV-infected adolescent females. CONCLUSIONS: Despite the younger age and shorter time since sexual debut, cervical cytological abnormalities and HPV infection were as common in perinatally HIV-infected as in behaviourally infected and uninfected adolescents. HPV vaccination, pre-cancer screening and antiretroviral treatment in HIV-infected female adolescents should be implemented to minimise the risk of cervical cancer.

HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. METHODS: We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. RESULTS: One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8-11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7-32.6) months, their median CD4 percentage was 12% (4-20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3-5.2) log(10) HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02-14.93] and plasma HIV RNA>5 log(10) copies/mL (OR 2.46; 95% CI 1.04-5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. CONCLUSIONS: In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance, including resistance to etravirine.

A drug dosage table is a useful tool to facilitate prescriptions of antiretroviral drugs for children in Thailand.

Scaling up of antiretroviral treatment (ART) for children in countries like Thailand will require decentralization and management by non-specialist doctors. We describe (a) the formulation of a standardized drug dosage table to facilitate antiretroviral drug (ARV) prescriptions for children, (b) the acceptability of such a table among doctors and (c) the safety and efficacy of drug doses in the table. Acceptability was assessed using a questionnaire. Safety and efficacy were assessed on the basis of incidence of adverse effects and virological response to treatment, respectively. Of all doctors (n=18), 17 (94%) found that the table was practical to use, avoided miscalculations and made them more confident with prescriptions. Of 49 children prescribed ARVs, less than 5% had adverse side-effects. All ARV-naïve children achieved undetectable viral loads within six months of ART. In our setting, a standardized drug dosage table provided a simple and reliable tool that facilitated ARV prescriptions for children.

Nosocomial pneumonia in a newborn intensive care unit.

Nosocomial pneumonia is a major cause of morbidity and mortality in hospitalized patients. The risk is especially high in the neonatal intensive care unit (NICU) particularly in infants with mechanically assisted ventilation. During the 5-year period of the study, 160 infants with problems including prematurity (60.6%), respiratory distress (55.6%) and birth asphyxia (45.0%) were admitted to the NICU. One hundred and thirty-three infants (83.1%) received mechanical ventilation. Nosocomial pneumonia was found in 65 infants (40.6%) or 88.3 cases per 1,000 ventilator-days. Low birth weight, prematurity, respiratory distress and hyperbilirubinemia were found more significantly in the pneumonia group. They underwent more manipulations such as the placement of an umbilical catheter and orogastric tube. Infants with pneumonia received mechanical ventilation at a higher percentage and for a longer period than those without pneumonia (96.9% vs 73.7%, odds ratio = 11.2, p = 0.000) with a mean duration of 11.7 and 3.5 days respectively (p = 0.000). The etiologic organisms recovered from hemoculture were Acinetobacter calcoaceticus var. anitratus 44.0 per cent, Enterobacter spp. 16.0 per cent, Klebsiella pneumoniae 16.0 per cent, coagulase-negative staphylococci 12.0 per cent. There was no concordance of the bacteriologic results in endotracheal aspirate culture and hemoculture in each infant. Leukocytosis and granulocytosis as well as blood gas values could not differentiate the presence of pneumonia. The mean hospital stay for the infants with pneumonia was longer (23.0 days vs 6.4 days, p = 0.000). Nosocomial pneumonia did not only prolong hospital stay but also contributed to mortality. Twenty-seven (41.5%) of the infants with pneumonia died, compared with 46 (48.4%) of the other group without pneumonia (p = 0.422). The risk of nosocomial pneumonia can be reduced by using infection control measures, including meticulous hand washing and gloving during respiratory manipulation, heat-treated water supply in a nebulizing unit of the ventilator and proper care of umbilical catheterization.