In sharp contrast, experimental SIVsm infection of rhesus macaque produces immune activation and AIDS-like disease with many parallels to human HIV infection.Delineating how CD4 T cells are depleted and how chronic inflammation and immune activation are induced lies at the heart of understanding HIV pathogenesis––one of the top priorities for HIV research by the Office of AIDS Research, National Institutes of Health. Recent studies demonstrated that caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death, drives CD4 T-cell depletion and inflammation by HIV. These are the two signature events that propel HIV disease progression to AIDS. Pyroptosis appears to create a pathogenic vicious cycle in which dying CD4 T cells and other immune cells (including macrophages and neutrophils) release inflammatory signals that recruit more cells into the infected lymphoid tissues to die. The feed-forward nature of this inflammatory response produces chronic inflammation and tissue injury. Identifying pyroptosis as the predominant mechanism that causes CD4 T-cell depletion and chronic inflammation, provides novel therapeutic opportunities, namely caspase-1 which controls the pyroptotic pathway. In this regard, pyroptosis of CD4 T cells and secretion of pro-inflammatory cytokines such as IL-1β and IL-18 can be blocked in HIV-infected human lymphoid tissues by addition of the caspase-1 inhibitor VX-765, which has already proven to be safe and well tolerated in phase II human clinical trials. These findings could propel development of an entirely new class of "anti-AIDS" therapies that act by targeting the host rather than the virus. Such agents would almost certainly be used in combination with ART.
Sadomasochism ( SAY-doh-MASS-ə-kiz-əm) is the giving and receiving of pleasure from acts involving the receipt or infliction of pain or humiliation. Practitioners of sadomasochism may seek sexual pleasure from their acts. While the terms sadist and masochist refer respectively to one who enjoys giving and receiving pain, some practitioners of sadomasochism may switch between activity and passivity.The abbreviation S&M is commonly used for Sadomasochism (or Sadism & Masochism), although the initialisms S-M, SM, or S/M are also used, particularly by practitioners. Sadomasochism is not considered a clinical paraphilia unless such practices lead to clinically significant distress or impairment for a diagnosis. Similarly, sexual sadism within the context of mutual consent, generally known under the heading BDSM, is distinguished from non-consensual acts of sexual violence or aggression. Definition and etymology
The word sadomasochism is a portmanteau of the words sadism () and masochism. The two words incorporated into this compound, "sadism" and "masochism", were originally derived from the names of two authors. The term "sadism" has its origin in the name of the Marquis de Sade (1740–1814), who not only practised sexual sadism, but also wrote novels about these practices, of which the best known is Justine. "Masochism" is named after Leopold von Sacher-Masoch (1836–1895), who wrote novels expressing his masochistic fantasies. These terms were first selected for identifying human behavioural phenomena and for the classification of  psychological illnesses or deviant behaviour.