Plasma HIV burden in Malawian children co-infected with rotavirus

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Fifty-eight HIV-infected children with acute rotavirus diarrhea were tested for plasma HIV RNA. There was no difference between acute and convalescent mean viral loads, and little change in the CD4 cell counts. Compared with the 16 children who died within 4 weeks, 31 survivors had slightly lower viral loads at presentation and significantly higher CD4 cell counts. Low CD4 cell counts, but not HIV-1-RNA concentrations, were predictive of death. Local, enteric rotavirus infection did not appear to affect blood HIV viral load or CD4 cell counts in this small group of children.
Rotavirus is an important cause of severe gastroenteritis in infants and young children worldwide. In developing countries, rotavirus infections account for 10–20% of deaths associated with gastroenteritis [1]. HIV is also prevalent in many developing countries, especially those in sub-Saharan Africa. In Malawi, approximately 30% of pregnant women are infected with HIV and 25–40% of their infants will become infected [2]. It is thus common for infants and children to be co-infected with these pathogens.
Concurrent infections with several pathogens have been associated with transient, but significant, increases in the blood plasma HIV load [3–7]. In other cases, the HIV load was significantly increased in the semen of men with urethritis [8] or bronchoalveolar lavage of individuals with Pneumocystis pneumonia [9], but not in concurrent blood specimens. The purpose of this study was to evaluate the difference in plasma HIV-1-RNA levels between acute and convalescent samples in a subset of children co-infected with rotavirus [10].
The parent study [10] enrolled 1186 children under 5 years of age with acute gastroenteritis. A total of 102 children were infected with both HIV and rotavirus. Of these, 44 were not sampled primarily because of lack of parental consent. Therefore, 58 HIV-infected children ranging in age from 1 to 19 months were tested for HIV-1 RNA. The Malawi National Health Sciences and Research Committee gave ethical approval for the study. Written, informed consent was obtained from the child's parents or guardians before enrolment.
A 10–20% (w/v) fecal suspension in phosphate buffered saline was tested for rotavirus antigen by enzyme-linked immunosorbent assay (ELISA; Rotaclone, Meridian Diagnostics, Cincinnati, OH, USA). Children older than 15 months were initially screened for HIV-1/HIV-2 antibodies using a rapid method (Serocard HIV, Trinity Biotech, Dublin, Ireland) and then screened by ELISA (Ortho Diagnostic Systems Ltd., Amersham, UK). Specimens that were reactive in the Ortho ELISA were confirmed using the Recombigen HIV-1/HIV-2 Rapid Test Device (Cambridge Diagnostics Ireland Ltd., Galway, Ireland). For children less than 15 months of age, a diagnosis of HIV infection was determined by an HIV DNA polymerase chain reaction using DNA from dried blood spots [11].
CD4 and CD8 T cell subsets were determined by FACScan flow cytometry (Becton-Dickinson, San Jose, CA, USA). HIV RNA was measured using the NucliSens assay (Organon Teknika, Durham, NC, USA) according to the manufacturer's instructions. Previous studies had determined that clade C is the predominant HIV-1 subtype in Malawi [12] and that the NucliSens assay accurately detects clade C [13,14].
An exploratory data analysis strategy was used. All reported P values should be interpreted accordingly. Linear mixed models were used to investigate the relationship between viral load (or CD4 cell count) and visit and survival. Logistic regression was used to model the probability of survival as a function of viral load and CD4 cell count. Transformations to log10 HIV-1-RNA copies/ml and to square root CD4 cell counts were used in the statistical analyses.
Fifty-eight HIV-infected children (28 females and 30 males) with acute rotavirus diarrhea were included. Their median age was 6.5 months (range 1–19 months). Thirty-one children were examined at follow-up 3–4 weeks later.

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