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Does IVDU Affect HIV Progression
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Study title: Modulation of Infection and Type 1 Cytokine Expression Parameters by Morphine During In Vitro Coinfection with Human T-Cell Leukemia Virus Type I and HIV-1
JAIDS Journal of Acquired Immune Deficiency Syndromes 2003; 32(4):406-416 Susan B. Nyland; Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Florida
In this study: "Impaired Virologic Response to Highly Active Antiretroviral Therapy Associated With Ongoing Injection Drug Use", Julio Montaner reviews findings of a lesser response to reducing HIV viral load to <500 copies/ml in active drug users compared to former IV drug users and non-drug users.
http://www.natap.org/2003/april/042103_6.htm
In the United States, HIV-1 infection occurs in approximately 0.3%
of the overall population and in up to 58% of IDUs, depending on the geographic region. Likewise, HTLV-I infection occurs in about 0.008% of the general population and in at least 0.6% of IDUs. Both HIV and the human T-cell leukemia viruses (HTLVs) can infect CD4 T cells, and coinfection occurs most frequently in IDUs. Of HIV-1-infected US residents, 0.05% to 6% are also infected with HTLV. In IDUs, the incidence of coinfection with HTLV increases to 12% to 24% of HIV-1-seropositive IDUs.
Opiates interact with transmembrane receptors to modulate the immune response. The majority of reports from in vitro and in vivo studies indicate that morphine inhibits T helper 1 (Th1) immune responses, usually starting with the inhibition of IL-2. Morphine also shortens the life span of T cells by
speeding up programmed cell death (PCD). Morphine has been reported to reduce the levels of interferons in the body, including IFN[gamma]. Thus, exposure to morphine or related opiates can lead to compromised type I
immunity and premature death of type I immune cells.
The major goal of this study was to determine what effect morphine has on HTLV-I infection in single- and dual-infection models (i.e., with HIV).
In cultured cells dually infected with HIV-1 and human T-cell leukemia virus type 1 (HTLV-1), exposure to morphine enhances HTLV-1 activity. In addition, morphine downregulated the expression of type I cytokines in most of the in vitro models tested, including HTLV-I infection alone. The important exception to this finding was highlighted by the correlation of increased IFN[gamma] and IL-2 with increased p19 in dually infected cultures. The enhancement of type I cytokine expression in dually infected cells could be a result of HTLV-I
amplification, which, if also occurring in vivo, might potentially pose a problem with immunotherapeutic treatments of coinfected IDUs.
The present study sought to determine how morphine could potentially affect the course of HTLV-I infection and HTLV-I/HIV-1 dual infection using in vitro models. The complexity of studying such retroviral infections, even when
in vitro models are used, is considerable. This study established that in vitro HTLV-I infection was enhanced by morphine when HTLV-infected cells were exposed to HIV-1. In addition, morphine downregulated the expression of
type I cytokines in most of the in vitro models tested, including HTLV-I infection alone. The important exception to this finding was highlighted by the correlation of increased IFN[gamma] and IL-2 with increased p19 in dually infected cultures. The enhancement of type I cytokine expression in dually infected cells could be a result of HTLV-I amplification, which, if also occurring in vivo, might potentially pose a problem with immunotherapeutic treatments of coinfected IDUs
Although immunotherapies to restore type I cytokine expression may benefit HIV-1-infected IDUs, such therapies might have an adverse effect on HTLV-I/HIV-1-coinfected patients. The current study of morphine on complex retroviral infections represents the in vitro activity of an in vivo metabolite of heroin. If the findings of the in vitro studies are confirmed in vivo, it may be appropriate and advantageous for coinfected IDUs to receive anti-inflammatory agents designed to inhibit the production of IL-6 instead of immune therapies designed to boost type I immunity. Previously published studies focusing on either HIV-1 or HTLV-I have inadequately prepared researchers and clinicians for the peculiarities of dual retroviral infection, especially in the IDU. The presence of HTLV-I is sometimes masked in HIV-1-seropositive individuals, so coinfection may be hidden. Yet, the importance of coinfection in the selection of patient treatment protocols should not be discounted, because the steps taken to control one retrovirus may inadvertently lead to the activation of the other. Subsequently, acknowledgment of this possibility could allow for better preparation against the deleterious consequences of such treatments.
Study abstract: Infection of injection drug users (IDUs) with the human T-cell leukemia viruses (HTLVs) or HIV is considerably higher than in the non-IDU population. Also, coinfection with HIV-1 and HTLV type I (HTLV-I) occurs more frequently. There is little or no information on the effects of opiates (i.e., morphine) on HTLV infection alone or on coinfection of HTLV-I-infected cells with HIV-1. Therefore, in this report, we analyzed the in vitro effects of morphine on HIV or HTLV infection alone as well as on dual infection with HTLV-I and HIV-1. Morphine decreased the in vitro levels of interferon-[gamma] (IFN[gamma]) and IL-2 during single infections, and this effect was reversed by the addition of the opioid antagonist naloxone. In contrast, treatment with morphine resulted in a 31% and 36% increase in IFN[gamma] and IL-2 levels, respectively, during dual infection. In addition, naloxone had an apparent additive effect on the morphine-associated enhancement of IFN[gamma] and IL-2 expression in the dual-infection model. Despite the high levels of IFN[gamma] expression, the viability of the coinfected cells in the presence of morphine was maintained. Importantly, morphine treatment was associated with augmented viral reverse transcription activity in dually infected cultures, apparently to the benefit of HTLV-I. If a similar putative morphine-induced advantage for HTLV-I production also occurs during in vivo coinfection, opiates such as morphine could contribute to the observed increased rate of HIV-1/HTLV-I infection in the IDU population in a more direct fashion than was previously believed.
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