In men with HIV, risk of developing new KS lesions predicted by HHV-8 factors, not CD4 count or VL

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The risk of an HIV-positive man developing the AIDS-defining cancer Kaposi’s sarcoma (KS) is linked to the amount of human herpes virus – 8 (HHV-8) in peripheral blood mononculear cells (PBMC) and oral fluids, rather than CD4 cell count or HIV viral load, according to an American study published in the 24th January 2003 edition of the journal AIDS.

The study also found that HHV-8 is likely to be orally transmitted.

Investigators recruited 91 men who were positive for both HHV-8 and HIV from two HIV clinics in Atlanta, Georgia, between 1996 and 1999. All the men were gay, and 57 had been diagnosed with KS. Seventy controls assessed to have a lower risk of HHV-8 were also enrolled to the study, including six non-gay HIV-positive men, and sixteen HIV-positive women, plus nine HIV-negative gay men and 39 HIV-negative people attending sexual health clinics.

Glossary

Kaposi's sarcoma (KS)

Lesions on the skin and/or internal organs caused by abnormal growth of blood vessels.  In people living with HIV, Kaposi’s sarcoma is an AIDS-defining cancer.

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

peripheral blood mononuclear cells (PBMCs)

Any blood cell having a round nucleus (e.g., a lymphocyte, a monocyte or a macrophage). These blood cells are a critical component in the immune system. 

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

oral

Refers to the mouth, for example a medicine taken by mouth.

Background data was collected from medical records and from a self-completed questionnaire. In addition, all trial participants provided blood and saliva samples, and semen was collected from men. Rectal swabs and brushes and urine samples were initially collected, but this was discontinued as so few samples tested positive for HHV-8.

Each specimen was tested for HHV-8 DNA.

Analysis of the results showed that men who were positive for both HIV and HHV-8, those with KS were likely more likely to have HHV-8 DNA in both PBMC (35%) and saliva (37%). HIV-positive men with HHV-8 but no KS lesions, had high prevalence of HHV-8 DNA in saliva (32.4%), but not PBMC (a little under 6%). Only one semen sample (from a man with no KS) and one rectal swab (from a man with KS) had HHV-8 DNA present.

Among the controls, the only positive results were from two men, both of whom had HHV-8 DNA present in both saliva and PBMC.

When the risk factors for the development of KS lesions were examined, it was found that the most important factor was the presence of HHV-8 DNA in PBMC, and this remained the case when low CD4 count and high HIV viral load were controlled for. In addition, in men with pre-existing KS, HHV-8 in PBMC was strongly associated with the risk of developing new KS lesions, and HHV-8 DNA in saliva was predictive of the risk of new oropharyngeal lesions.

Interestingly, men with high HHV-8 antibody titres were more likely to have KS, but not to develop new lesions, suggesting a protective effect and an avenue of future HHV-8 vaccine research to the research team.

The investigators suggest that their study has “identified several new findings relating to HHV-8 DNA as a risk factor for KS”. In men with KS, there was an association between new lesions and HHV-8 DNA in PBMC; and, HHV-8 DNA in the saliva of men was KS was associated with an increased risk of new oropharyngeal lesions.

The investigators also stress that their findings suggest that HHV-8 DNA in PBMC is “more strongly linked to KS than either low CD4 cell count or high HIV viral load.” They add “we found that the associations between KS…and HHV-8 DNA were not simply due to deficient immune function in men with HIV…this is the first study that has evaluated these associations while controlling for potential confounding factors linked to immunosuppression (eg HIV viral load and CD4 cell count).”

Regarding the transmission of HHV-8, the investigators suggest that their findings suggest an oral mode given the high prevalence of HHV-8-positive men with HHV-8 DNA in their saliva. Transmission by oral-genital contact (rimming) and by exposure to semen were not supported by the study findings.

Further information on this website

Kaposi’s sarcoma – overview

Kaposi’s sarcoma – Factsheet

Cancers – overview

PI and NNRTI regimens equally effective at treating KS, says study – news story

References

Cannon MJ et al. Risk factors for Kaposi’s sarcoma in men seropositive for both human herpes virus 8 and human immunodeficiency virus. AIDS 17: 215-222, 2003.