Howard D. Strickler

Investigation of Human Urine for Genomic Sequences of the Primate Polyomaviruses Simian Virus 40, BK Virus, and JC Virus

Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses BK virus (BKV) and JC virus (JCV). Tests with masked urine specimens spiked with SV40-transformed cells were included to monitor the SV40 assay. SV40, BKV, and JCV sequences were identified, respectively, in 0, 14%, and 34% of the urine specimens. JCV viruria was far more common (37%) than BKV viruria (5%) in HIV-seronegative persons. HIV infection and more severe immunosuppression were associated with a higher frequency of BKV viruria. In summary, SV40 viruria was not detected among homosexual men who shed human polyomaviruses at a high frequency.

A survey of human papillomavirus 16 antibodies in patients with epithelial cancers

Human papillomavirus (HPV), particularly HPV 16, is linked to the development of cervical cancer. However, the role of HPV 16 in a number of extra-cervical epithelial tumours is controversial. To assess exposure to HPV 16 in patients with different cancers, we conducted a large serosurvey of 905 patients with 21 types of tumours and measured IgG to HPV 16 virus-like particles (VLPs) using a well characterized enzyme linked immunosorbent assay (ELISA). Patients with cervical cancer were considered positive controls, as about half were expected to be specifically HPV 16-related. A non-cancer study group consisting of 48 patients with endocrine disorders (eg diabetes) was also tested. HPV 16 antibody prevalence was highest in patients with cancers of the cervix (52% ± 7%), vulva (27% ± 9%), vagina (27% ± 13%) and penis (63% ± 16%). Seroprevalence was much lower in the non-cancer group (4% ± 3%) and all other cancer patients: uterus (9% ± 4%); ovary (4% ± 3%); testis (5% ± 4%); prostate (6% ± 4%); squamous carcinoma (6% ± 3%) and adenocarcinoma (4% ± 3%) of the lung; rectum (2% ± 2%); pancreas (8% ± 4%); colon (2% ± 2%); stomach (0%); oesophagus (8% ± 4%); buccal cavity (12% ± 5%); breast (10% ± 4%); non-melanomatous (9% ± 6%) and melanomatous (6% ± 3%) skin tumours; bladder (8% ± 4%); and kidney (2% ± 2%). The results confirm the strong relation of HPV with several lower anogenital tract tumours, but, at least in this population, fail to identify additional epithelial tumours associated with high seroprevalence of HPV 16 VLP antibodies.

Human Herpesvirus 8 Cellular Immune Responses in Homosexual Men

Little is known about cellular immunity to human herpesvirus 8 (HHV-8), the virus associated with Kaposis sarcoma (KS). T cell proliferative responses to purified HHV-8 were measured in homosexual men, a group with elevated HHV-8 seroprevalence and high risk of KS. None of 20 blood donor controls had T cell responses to HHV-8. Among human immunodeficiency virus (HIV)-negative homosexual men, 8 (42%) of 19 HHV-8 seropositive men responded as did 4 (16%) of 25 HHV-8 seronegative men. Among HIV-positive homosexual men, however, none of 21 HHV-8 seropositives had T cell responses to HHV-8, even though most responded to common recall antigens, and 10 had >/=400 CD4 cells/mm3. The results suggest that HHV-8 T cell proliferative responses are common in HIV-negative homosexual men and that HIV infection may be associated with diminished HHV-8 cellular immunity, possibly before there is substantial depletion of CD4 cells. If correct, this could explain why KS occurs relatively early in HIV infection/AIDS.

Problems in interpreting HIV sentinel seroprevalence studies

Estimating human immunodeficiency virus (HIV) prevalence from sentinel seroprevalence studies is difficult. We characterize these studies and show that most are investigations of incompletely defined (hypothetical) cohorts and are usually based on nonprobability samples. Prevalence in HIV sentinel serosurveys is also time-averaged and vulnerable to several time-dependent sources of bias (e.g., migration, deaths, and changes in incidence). Assumptions must be made that these time-dependent biases did not meaningfully affect the data, and this can be helped by reducing the period of investigation. Furthermore, we show that reliability can not be adequately measured by standard error, that internal validity is vulnerable to self-selection bias and laboratory problems, and that generalizability is limited. We propose that what is needed is a procedure (like formal metaanalysis methods) incorporating information from several separate HIV sentinel seroprevalence studies, in a manner that is reproducible and can take into consideration the differences between studies.

Elevated serum levels of neopterin but not β2-microglobulin in HIV-1-seronegative injecting drug users

ObjectiveTo determine whether injecting drug use is associated with cellular immune activation in the absence of HIV-1 infection. DesignSerum levels of neopterin and β2-microglobulin (β2M) were measured cross-sectionally in injecting drug users (IDU) enrolled in a prospective study. Subjects and methodsTwo hundred and nineteen HIV-1-seronegative, healthy heterosexual black male IDU aged 21–49 years were selected from the Baltimore-based AIDS Linked to Intravenous Experiences (ALIVE) study. The possibility of including subjects in the process of seroconverting to HIV-1 was minimized by restricting the study to individuals who remained seronegative 6 months after the specimens used for analysis were collected. ResultsMean serum β2M levels were not statistically different among groups of IDU whose usual pattern of injection was at least once a day for up to 3 consecutive days (daily users; n = 65), less than once per day (less-than-daily users; n = 75), or not at all for at least 2 weeks (non-recent users; n = 79). In contrast, the mean neopterin level was significantly (P = 0.039) greater in daily users (6.17nmol/l) than in the other two groups (5.07 and 5.19nmol/l, respectively, which were not statistically different). These results were not affected, by the frequency of using borrowed non-sterile works or by other demographic and risk factor variables. ConclusionsFrequent injecting drug use may be independently associated with a small elevation of serum neopterin levels, but not β2M levels. Although the occurrence of a type I error in this sample cannot be completely excluded, serum neopterin may be more sensitive than serum β2M in detecting activation of immunocompetent cells associated with frequent injecting drug use in this population.