PubMed · 7763436
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
P H Duesberg. 1993. HIV latency.. https://doi.org/10.1038/nbt0393-247a
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The spectrum of HIV-related lymphoid malignancies certainly includes non-Hodgkin's lymphoma (NHL; i.e., chiefly large-cell lymphoma and Burkitt's lymphoma), primary lymphoma of the brain (PBL) and, possibly, Hodgkin's disease (HD). Since the mid-1990s, several epidemiological studies have led to better quantification of the burden of lymphomas in HIV-infected populations. AIDS surveillance data from 17 western European countries show that between 1988 and 1997 a total of 7,148 AIDS cases had NHL as the AIDS-defining illness. The yearly number of cases rose steadily from 1988 to 1995 but declined thereafter. As a percentage of AIDS-defining illnesses, NHL increased from 3.6% in 1994 to 4.9% in 1997. Percent increases were observed in different strata by area, age group, sex and HIV-transmission group. To estimate relative risk (RR) of NHL and other lymphoid neoplasms in unselected HIV-seropositive populations, records of population-based cancer registries and AIDS registries were linked in the United States, Italy and Australia. RRs for NHL in adults with HIV/AIDS ranged between 14 (for low-grade NHL) to over 300 (for high-grade NHL). For HD, the RR was approximately 10. Limited findings from studies based on death certificates and cohorts of HIV-seropositive persons were consistent with those from registry linkage studies. In developing countries, the risk of HIV-associated NHL appears to be much lower than in developed countries, but under-ascertainment and earlier death from other AIDS manifestations may explain the lack of HIV-associated lymphomas in Africa.
The beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta suppress infection by macrophage-tropic strains of HIV and simian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of CCR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Cohort Study at the Baltimore site was conducted to measure chemokine production and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC). Statistical analyses of the data revealed that the production of HIV-suppressive beta-chemokines by HIV antigen-stimulated PBMC was significantly higher in HIV-positive subjects without AIDS compared with subjects with clinical AIDS. Increased chemokine production was also correlated with higher proliferative responses to HIV antigens. Both parameters were significantly lower in the AIDS versus non-AIDS group. Notably, significantly higher levels of MIP-1alpha were also observed with unstimulated PBMC from seronegative subjects at risk for HIV infection released as compared with seropositive and non-Multicenter AIDS Cohort Study seronegative subjects. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.
Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.