Archive for the ‘H.I.V.’ Category

The effects of recreational drugs on CD4 and CD8 T cells in humans are not well understood. We conducted a longitudinal analysis of men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study to define associations between self-reported use of marijuana, cocaine, poppers and amphetamines, and CD4 and CD8 T cell parameters in both HIV-uninfected and HIV-infected MSM. For the HIV-infected MSM, we used clinical and laboratory data collected semiannually before 1996 to avoid potential effects of antiretroviral treatment. A regression model that allowed random intercepts and slopes as well as autoregressive covariance structure for within subject errors was used. Potential confounders adjusted for included length of follow-up, demographics, tobacco smoking, alcohol use, risky sexual behaviors, history of sexually transmitted infections, and antiviral therapy. We found no clinically meaningful associations between use of marijuana, cocaine, poppers, or amphetamines and CD4 and CD8 T cell counts, percentages, or rates of change in either HIV-uninfected or -infected men. The regression coefficients were of minimum magnitude despite some reaching statistical significance. No threshold effect was detected for frequent (at least weekly) or continuous substance use in the previous year. These results indicate that use of these substances does not adversely affect the numbers and percentages of circulating CD4 or CD8 T cells in either HIV-uninfected or -infected MSM.

Anthraquinones and structurally related compounds have been recently shown to exert antiviral activities and thus exhibit a therapeutic potential. In this study we report the isolation of the 1,4-phenanthrenequinone, denbinobin, from a variety of Cannabis sativa. Denbinobin does not affect the reverse transcription and integration steps of the viral cycle but prevents HIV-1 reactivation in Jurkat T cells activated by TNFalpha, mAbs anti-CD3/CD28 or PMA. In addition, denbinobin inhibits HIV-1-LTR activity at the level of transcription elongation and also TNFalpha-induced HIV-1-LTR transcriptional activity. We found that denbinobin prevents the binding of NF-kappaB to DNA and the phosphorylation and degradation of NF-kappaB inhibitory protein, IkappaBalpha, and inhibits the phosphorylation of the NF-kappaB p65 subunit in TNFalpha-stimulated cells. These results highlight the potential of the NF-kappaB transcription factor as a target for natural anti-HIV-1 compounds such as 1,4-phenanthrenequinones, which could serve as lead compounds for the development of an alternative therapeutic approach against AIDS.

Published 28 October 2008 in Biochem Pharmacol, 76(10): 1240-50.
Full-text of this article is available online (may require subscription).

Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Δ-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size=0.60; p=0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.

ISLAMABAD: Short-term cannabis use does not seem to adversely affect CD4+ cell counts or viral loads in HIV -infected patients, according to a report published in the August 19th issue of the Annals of Internal Medicine.

In HIV-infected patients, marijuana has been used as an appetite stimulant and as a treatment for the nausea associated with some antiretroviral agents. However, concern has been raised that such therapy could have a harmful effect on disease status, because in theory, cannabinoid use could increase HIV levels by impairing the immune response or by interfering with the activity of protease inhibitors.

Previously it was shown that short-term marijuana use did not influence nelfinavir metabolism. Although marijuana use did produce a drop in indinavir levels, this fall was small and unlikely to be clinically meaningful. However, it still remained unclear whether cannabinoid use had an effect on viral load or CD+ cell counts.

To investigate, Dr. Donald I. Abrams, from the University of California at San Francisco, and colleagues assessed the outcomes of 67 HIV-infected patients who were randomly assigned to use marijuana cigarettes, cannabinoid capsules, or sugar pills (placebo) three times daily for 21 days. All of the patients had been receiving the same antiretroviral regimen, which included indinavir or nelfinavir, for at least 8 weeks before the study began.

More than half of the subjects in each group had undetectable viral loads throughout the study, the researchers note. Although not statistically significant, marijuana and cannabinoid use were actually associated with a slight drop in viral load compared with placebo use.

Marijuana and cannabinoid use did not produce a drop in CD4+ or CD8+ cell counts. In fact, compared with placebo use, treatment with these agents was actually associated with a slight increase in cell counts.

The results suggest that short-term cannabinoid use is not unsafe for patients with HIV infection, the authors note. “Further studies investigating the therapeutic potential of marijuana and other cannabinoids in patients with HIV infection and other populations are ongoing and should provide additional safety information over longer exposure periods,” they write.