AEGiS-13IAC: Acute PCP increases HIV-1 replication in vivo and expands viral chemokine receptor tropism.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Acute PCP increases HIV-1 replication in vivo and expands viral chemokine receptor tropism.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA345)

Shaunak S, Veryard C, Buttigieg K, Javan C
S. Shaunak, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, London. W12 0NN, United Kingdom, Tel.: + 44 208 383 2301, Fax: + 44 208 383 3394, E-mail: s.shaunak@ic.ac.uk

BACKGROUND: Many opportunistic infections (OI) induce pro-inflammatory cytokine release and promote T cell activation in vitro. We investigated the effect of Pneumocystis carinii pneumonia (PCP), CMV and HSV on HIV-1 replication and chemokine receptor usage during acute episodes of these infections.

METHODS: Blood was collected regularly from clinically well patients attending clinics, and again when they became acutely ill. A PHA/IL-2 induced HIV replication assay (PIVLA) was used to determine the frequency of resting CD4+ T cells carrying replication-competent forms of HIV-1. The experimental conditions used allow HIV-1 to replicate in > 95% of T cells which contain integrated HIV-1 DNA. All viral isolates were also phenotyped for their use of the chemokine receptors CCR1, CCR2b, CCR3, CCR5 and CXCR4.

RESULTS: 62 patients were followed for an average of 2 consecutive years. There were 29 cases of proven acute PCP, 11 cases of acute disseminated CMV infection and 18 cases of acute herpes simplex virus type 1 infection (HSV). The PIVLA assay was usually negative (ie: 456 `0' é 269 pg/ml; mean `median' é sem) when performed on clinically well patients. The PIVLA result for PCP was 3,185 `2,050' é 686 pg/ml, for CMV was 1,241 `0' é 598 pg/ml, and for HSV was 451 `175' é 157 pg/ml. The result for PCP was higher than that for CMV (p = 0.038) or HSV (p = 0.002). The CMV and HSV results are not significantly different from those in clinically well patients (p > 0.05). The number of chemokine receptors used by HIV-1 increased during PCP. Three months after recovering, viral chemokine receptor tropism had reverted back to its pre-OI pattern.

CONCLUSIONS: The frequency of cells containing integrated, replication competent forms of HIV-1 increases during PCP, but not during disseminated CMV or active herpes simplex virus type 1 infection. Acute PCP is also associated with a short-term increase in the number of chemokine receptors being used by HIV-1.

Keywords: AEGIS, Receptors, Chemokine, HIV-1, Virus Replication, Tropism, HIV Infections, Antigens, CD4, Pneumonia, Pneumocystis, HIV Seropositivity, HIV-1 Reverse Transcriptase, Cytomegalovirus Infections, In Vitro, Human, virology, immunology
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TuOrA345