The influence of MT-2 tropism on the prognostic implications of the delta32 deletion in the CCR-5 gene.
BACKGROUND
Long-term non-progression in HIV-1-infected patients has been reported to be associated with a 32 base-pair deletion (delta32) in one CCR-5 allele. The normal gene product acts as a coreceptor for HIV cell entry and is essential for infection of cells by non-syncytium-inducing and MT-2-negative HIV-1 strains.


METHODS
Forty individuals were studied, all of whom had been HIV-1-seropositive for a mean of 8 years.


RESULTS
Eight (20%) were heterozygous for the CCR-5 allele delta32 deletion. Six of these eight patients harboured MT-2-negative HIV-1 strains. Of these six, three were long-term non-progressors with a positive CD4 cell slope, not receiving antiretroviral treatment, whereas the other three were progressors (mean CD4 cell decline, 3.8 x 10(6)/l per month) receiving antiretroviral combination therapy. Two of the eight patients with the delta32 deletion had MT-2-positive HIV-1 strains. Both had very rapid CD4 cell decline (6.7 and 7.6 x 10(6)/l per month, respectively), despite triple antiretroviral therapy including a protease inhibitor. One of the patients with an MT-2-positive virus strain has suffered from Pneumocystis carinii bronchitis and the other from cytomegalovirus colitis.


CONCLUSIONS
Disease progression may also occur in individuals with the coreceptor deficiency, especially in association with MT-2-positive HIV-1 strains. It is suggested that MT-2-positive HIV-1 enters cells through the CXC chemokine receptor-4 fusin coreceptor, thus circumventing the defective CC chemokine receptor-5 coreceptor. Various levels of expression of the wild-type CCR-5 gene and the gene with the delta32 deletion might explain variations in the disease progression in heterozygous patients with MT-2-negative HIV-1 strains.
Bratt
G
G
Gay Men's Health Clinic, the Department of Dermatovenereology, Stockholm Söder Hospital, Sweden.
Sandström
E
E
Albert
J
J
Samson
M
M
Wahren
B
B
D000328:Adult; D000483:Alleles; D017353:Gene Deletion; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D007114:Immunization; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics*; D017741:Survivors; D019562:Viral Load
D019302:HIV Envelope Protein gp160; D019713:Receptors, CCR5