Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

We conducted a study to identify the viruses in tissue specimens of oral "hairy" leukoplakia, a lesion that is found in immunosuppressed male homosexuals and that is associated with the subsequent development of the acquired immunodeficiency syndrome. When stained for papillomavirus core antigen, 49 of 67 biopsy specimens (73 per cent) yielded positive results in epithelial-cell nuclei. Electron microscopy showed papillomavirus-like particles in all of 25 specimens, and the herpes-type virus described in a previous report was seen in 23 of the 25 specimens. Three specimens had both types of particle in the same individual epithelial cells. Immunofluorescence for herpes simplex virus, varicella-zoster virus, and cytomegalovirus gave negative results in all cases, but 19 of 20 specimens showed intense nuclear staining in epithelial cells for the viral capsid antigen of Epstein-Barr virus (EBV). DNA hybridization using EBV probes in Southern blots demonstrated EBV DNA in all of 13 specimens and found 200 or more viral DNA molecules per cellular genome in 11 of the 13. The whole EBV genome was also demonstrated in the specimens and found to be in linear virion form. We conclude that EBV replicates within the epithelial cells in hairy leukoplakia.

In patients failing triple drug therapy, GART with expert advice was superior to no-GART as measured by short-term viral load responses.

Objective To evaluate the risk of cancers with and without a known infectious cause in HIV-infected persons. Design Retrospective cohort study. Methods Adult HIV-infected and matched HIV-uninfected members of Kaiser Permanente followed between 1996 and 2007 for incident AIDS-defining cancers (ADC), infection-related non-AIDS-defining cancers (NADC) (anal squamous cell, vagina/vulva, Hodgkin’s lymphoma, penis, liver, HPV-related oral cavity/pharynx, stomach) and infection-unrelated NADC (all other NADC). Results We identified 20,277 HIV-infected and 202,313 HIV-uninfected persons. HIV-infected persons experienced 552 ADC, 221 infection-related NADC, and 388 infection-unrelated NADC. HIV-uninfected persons experienced 179 ADC, 284 infection-related NADC, and 3,418 infection-unrelated NADC. The rate ratio (RR) comparing HIV-infected and HIV-uninfected persons for ADC was 37.7 (95% CI: 31.7–44.8), with decreases in the RR over time (p<0.001). The RR for infection-related NADC was 9.2 (95% CI: 7.7–11.1), also with decreases in the RR over time (p<0.001). These results were largely influenced by anal squamous cell cancer and Hodgkin’s lymphoma. The RR for infection-unrelated NADC was 1.3 (95% CI: 1.2–1.4), with no change in the RR over time (p=0.44). Among infection-unrelated NADC, other anal, skin, other head and neck, and lung cancer rates were higher and prostate cancer rates lower in HIV-infected persons. Among all infection-unrelated NADC, the RR decreased over time only for lung cancer (p=0.007). Conclusions HIV-infected persons are at particular risk for cancers with a known infectious cause, although the higher risk has decreased in the antiretroviral therapy era. Cancers without a known infectious cause are modestly increased in HIV-infected persons.

We report a method for introducing a glutamine synthetase (GS) selectable marker into myeloma cells in which transfectants are selected by growth in a glutamine-free medium. Vector amplification can subsequently be selected using the specific inhibitor of GS, methionine sulphoximine (MSX). Using this system, DNA sequences encoding a chimeric B72.3 IgG4 antibody were expressed from hCMV-MIE promoters in NSO myeloma cells. A cell line was isolated after a single round of selection for vector amplification which contains approximately 4 copies of the vector, secretes 10-15 pg/cell/day cB72.3 antibody during exponential growth and can accumulate 560 mg/l antibody in a fed-batch air-lift fermentation system. Productivity is stable in the absence of MSX selection.

Higher CD4+ counts on antiretroviral therapy are associated with lower rates of non-AIDS diseases and AIDS. These findings expand our understanding of the implications of HIV-related immunodeficiency and motivate randomized studies to evaluate the effects of antiretroviral therapy on a broad set of clinical outcomes at CD4+ counts greater than 350 cells/microl.

Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustained-release morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2-4, and in the morning of day 5. Blood sampling was performed at 12-h intervals on days 1 and 5. The extent of chronic pain was also assessed daily. Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration-time curves for either morphine or oxycodone after exposure to cannabis. Pain was significantly decreased (average 27%, 95% confidence interval (CI) 9, 46) after the addition of vaporized cannabis. We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels. The combination may allow for opioid treatment at lower doses with fewer side effects.

Background Few studies have compared cancer risk between HIV-infected individuals and a demographically-similar HIV-uninfected internal comparison group, adjusting for cancer risk factors. Methods We followed 20,775 HIV-infected and 215,158 HIV-uninfected individuals enrolled in Kaiser Permanente (KP) California for incident cancer from 1996–2008. Rate ratios (RR) were obtained from Poisson models comparing HIV-infected (overall and stratified by recent CD4 count and HIV RNA) with HIV-uninfected individuals, adjusted for age, sex, race/ethnicity, calendar period, KP region, smoking, alcohol/drug abuse, and overweight/obesity. Results We observed elevated RRs for Kaposi sarcoma (KS) (RR=199; P<0.001), non-Hodgkin lymphoma (NHL) (RR=15; P<0.001), anal cancer (RR=55; P<0.001), Hodgkin lymphoma (HL) (RR=19; P<0.001), melanoma (RR=1.8; P=0.001), and liver cancer (RR=1.8; P=0.013), a reduced RR for prostate cancer (RR=0.8; P=0.012), and no increased risk for oral cavity/pharynx (RR=1.4; P=0.14), lung (RR=1.2; P=0.15), or colorectal (RR=0.9; P=0.34) cancers. Lung and oral cavity/pharynx cancers were elevated for HIV-infected subjects in models adjusted only for demographics. KS, NHL, anal cancer, HL, and colorectal cancer had significant (P<0.05) trends for increasing RRs with decreasing recent CD4. The RRs for lung and oral cavity/pharynx cancer were significantly elevated with CD4 <200 cells/µL and for melanoma and liver cancer with CD4 <500 cells/µL. Only KS and NHL were associated with HIV RNA. Conclusion Immunodeficiency was positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors. Impact Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population.