Severe Pneumocystis carinii pneumonia increases the infectious titre of HIV-1 in blood and can promote the expansion of viral chemokine co-receptor tropism.
OBJECTIVE
Determine the in vivo effect of Pneumocystis carinii pneumonia (PCP) on: (a) the titre of infectious virus circulating in blood; and (b) the chemokine co-receptor usage of these viruses.


METHODS
A longitudinal study of 62 patients over 8 years. The results for PCP were compared with those for disseminated cytomegalovirus (CMV) and acute herpes simplex virus type 1 infections (HSV). Blood was collected every 3-4 months when patients were well, and again when they were acutely ill. A tissue culture based PHA/IL-2 induced HIV replication assay was used to determine the frequency of circulating cells in blood carrying infectious forms of HIV-1. Viral isolates were phenotyped using U87 cells transfected with CD4 and a chemokine co-receptor.


RESULTS
There were 29 cases of PCP, 18 cases of HSV and 11 cases of CMV. A significant increase in the viral replication assay was seen during severe PCP but not during HSV or CMV infections. The number of chemokine co-receptors being used by HIV-1 increased during severe PCP to include CXCR4 and CCR3 in three of six patients from whom viruses were available for detailed study.


CONCLUSIONS
Severe PCP can increase the number of PBMN cells containing integrated, replication competent, infectious forms of HIV-1 circulating in blood. The expanded chemokine co-receptor tropism of these viral isolates could promote the dissemination of HIV-1 from lymphoid to non-lymphoid organs and explain the poor prognosis of patients who develop severe PCP.
Shaunak
S
S
Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, London, UK. s.shaunak@ic.ac.uk
Veryard
C
C
Javan
C
C
D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000175:diagnosis*; D000208:Acute Disease; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000821:virology; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006561:Herpes Simplex / Q000175:diagnosis / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D011010:Pneumocystis / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D054397:Receptors, CCR3; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D012720:Severity of Illness Index; D019562:Viral Load
C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine