Recombinant HIV type 1 (p63358.p3.4013) Glycoprotein 120 (a.a. 31-524) [His]

HIV infection and drug use intersect epidemiologically, and their combination can result in complex effects on brain and behavior. The extent to which drugs affect the health of persons with HIV (PWH) depends on many factors including drug characteristics, use patterns, stage of HIV disease and its treatment, comorbid factors, and age. To consider the range of drug effects, we have selected two that are in common use by PWH: methamphetamine and cannabis. We compare the effects of methamphetamine with those of cannabis, to illustrate how substances may potentiate, worsen, or even buffer the effects of HIV on the CNS. Data from human, animal, and ex vivo studies provide insights into how these drugs have differing effects on the persistent inflammatory state that characterizes HIV infection, including effects on viral replication, immune activation, mitochondrial function, gut permeability, blood brain barrier integrity, glia and neuronal signaling. Moving forward, we consider how these mechanistic insights may inform interventions to improve brain outcomes in PWH.

Objectives: Complement C3d receptor 2 (CR2) is the main receptor for complement protein C3d and plays an important role in adaptive immune responses. CR2 genetic variants are associated with susceptibility to systemic lupus erythematosus as well as to HIV-1 infection. In addition, CR2 function can be subverted by HIV-1 for an efficient entry into target cells; in a process known as antibody-dependent enhancement of viral infection. We sought to determine the association betweenCR2gene variants with HIV-1 acquisition after vaccination with recombinant gp120 protein (Vax004 clinical trial). Design and methods: This is a retrospective cross-sectional study, comprising male volunteers of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for three single nucleotide polymorphisms (SNPs) in theCR2gene region. Results: An interaction was observed between the baseline sexual behavior and the SNP rs3813946 for higher risk of infection in vacinees (interaction termP = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in volunteers with low behavioral risk odds ratio (95% confidence interval): 5.5 (1.4-21.7)P = 0.006 but not vaccinees with high behavioral risk or volunteers given placebo (P = 0.7). Moreover,CR2genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low-risk volunteers [hazard odds ratio (95% confidence interval): 3.3 (1.6-7.0),P = 0.001]. Conclusion: The current study suggests thatCR2may play a role in HIV-1 acquisition after vaccination with rgp120 proteins.