BackgroundOur intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London.MethodsA random sample of 861 HIV-1-infected patients attending HIV clinics at King's and St Thomas' hospitals' were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Subtypes were compared on the rate of CD4 cell decline using a multi-level random effects model. Virological response to ART was compared using the time to virological suppression (< 400 copies/ml) and rate of virological rebound (> 400 copies/ml) following initial suppression.ResultsComplete subtype and epidemiological data were available for 679 patients, of whom 357 (52.6%) were white and 230 (33.9%) were black African. Subtype B (n = 394) accounted for the majority of infections, followed by subtypes C (n = 125), A (n = 84), D (n = 51) and CRF02-AG (n = 25). There were no significant differences in rate of CD4 cell decline, initial response to highly active antiretroviral therapy and subsequent rate of virological rebound for subtypes B, A, C and CRF02-AG. However, a statistically significant four-fold faster rate of CD4 decline (after adjustment for gender, ethnicity and baseline CD4 count) was observed for subtype D. In addition, subtype D infections showed a higher rate of virological rebound at six months (70%) compared with subtypes B (45%, p = 0.02), A (35%, p = 0.004) and C (34%, p = 0.01)ConclusionsThis is the first study from an industrialized country to show a faster CD4 cell decline and higher rate of subsequent virological failure with subtype D infection. Further studies are needed to identify the molecular mechanisms responsible for the greater virulence of subtype D.
Between May 1, 1976, and May 14, 1977, 343 (32.5%) of 1056 5-day-old babies in newborn nurseries excreted rotaviruses. The infection-rate was highest during winter (49%). 76% of infected babies at this time were bottle-fed. 41% of neonates excreted low amounts of virus (less than or equal to 10(8) particles/g faeces); older children tended to excrete greater than 10(10) particles/g faeces. Infected breast-fed babies excreted less virus than those who were bottle-fed. Stools of breast-fed babies often contained clumps of complete "smooth" rotavirus particles. When the newborn nurseries were transferred to a newly built hospital wing, infection appeared in the new wards, including those admitting only new patients, within a short period. Infection was either mild (8%) or symptomless (92%), and even babies with symptoms required no treatment.
SUMMARYAbnormal RNA migration profiles were found in numerous rotavirus samples from two chronically infected children suffering from severe combined immunodeficiency. In both cases additional bands consisting of dsRNA were found migrating between RNA segments 1 and 7, and in one case RNA segment 11 was lost from the profile. Hybridization studies using segment-specific cloned cDNA probes indicated that some of the additional bands had sequence homologies with normal rotavirus dsRNA segments. In most cases these sequences were derived from genome segments of lower molecular weight by the formation of covalently linked concatemers.
Enteric virus infections were studied in two children with congenital T-cell immunodeficiency. One patient (LC) with cartilage hair hypoplasia developed persistent diarrhea and malabsorption following acute gastroenteritis. Electron microscope (EM) examination of feces revealed excretion of rotavirus for more than 450 days with concurrent astrovirus infection for at least 225 days, associated with the persistent diarrhea. Prolonged infection with poliovirus type 2 following vaccination had previously been noted in this patient. The second patient (DT), with the CHARGE association and DiGeorge syndrome, had two episodes of loose stools. EM of fecal extracts demonstrated rotavirus excretion for at least 66 days following the initial episode. Virus-specific immune responses were assayed in these two patients. LC showed a poor serum neutralizing antibody response to polio vaccination, no detectable antibody response (by immune EM and ELISA) to rotavirus, and no detectable antibody response to astrovirus (by immune EM). Rotavirus specific cell mediated immunity was also not detectable. DT showed no detectable serum antibody response to rotavirus (by ELISA). Rotavirus isolates from both patients were found to be group A viruses and were further analyzed by polyacrylamide gel electrophoresis. Atypical genome profiles, with multiple additional bands between segments 3-7 of the normal rotavirus profile, were obtained throughout the course of each illness, including the earliest specimens available (day 41, LC; day 7, DT). These results indicate that chronic virus infection of the gut can occur in patients with T-cell immunodeficiency. Such chronic infection may be associated with persistent diarrhea and can cause considerable problems of management.
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