Alberta Reappraising AIDS Society

David Crowe, President
Phone: +1-403-289-6609
Fax: +1-403-206-7717
Email: David.Crowe@aras.ab.ca

Kathleen Newell, Treasurer
Box 61037, Kensington Postal Outlet
Calgary, Alberta T2N 4S6
Canada
Office
Phone: +1-403-220-0129
Email: aras@aras.ab.ca
Web: aras.ab.ca

There has long been an association between recreational drugs and AIDS. Surprisingly, some of the strongest associations are not with injection drugs, but with inhalant nitrites, widely marketed to and used by gay men, and with non-injection forms of cocaine, such as ‘crack’. This information is largely ignored by people who accept the infectious theory of AIDS, perhaps because this evidence does not fit that theory.

The quotes are categorized as:

  • Cocaine use and HIV/AIDS
  • General Health Risks of Recreational Drugs
  • IV Drug Abuse
  • Mothers, Drugs, HIV and AIDS
  • Needle Exchange Programs
  • Nitrite Inhalants
  • Cocaine use and HIV/AIDS

    Cocaine use is closely associated with the risk of testing positive for HIV and having AIDS - even if the usage is non-injection!

    “Data from 1686 women were analyzed: 1203 (71.4%) were categorized as non-users, 429 (25.4%) as intermittent users, and 54 (3.2%) as persistent users of crack [cocaine]…There were 419 deaths during the follow-up period: 197 (47.0%) were AIDS-related, 138 (33.0%) were non- AIDS-related, and 84 (20.0%) were indeterminate…In a Cox proportional hazards model adjusting for age, race, income, education, problem drinking, adherent HAART-use, CD4 cell count less than 200 cells/µl at baseline, HIV-1 RNA level more than 100 000 copies/ml at baseline, illness duration, and study site, compared with that for non-users, the risk of AIDS-related death was significantly higher for persistent users but not for intermittent users. Of the total group of 1686 women, 543 (32.2%) were found to have a newly acquired AIDS-defining illness during the follow-up period. Significantly higher proportions of intermittent users (42.0%) and persistent users (38.9%) reported a new illness during this time period than did non-users (28.4%). The most frequently reported AIDS-defining illnesses were bacterial pneumonia (18% of all cases), pneumocystis carinii pneumonia (10%), herpes simplex virus, non-pulmonary (9%), esophageal candidiasis (9%), cryptosporidiasis (6%), dementia/ encephalopathy (5%), wasting syndrome (5%), and tuberculosis (4%). Among these, persistent and/or intermittent users were [statistically] significantly more likely than non-users to report bacterial pneumonia, tuberculosis, and esophageal candidiasis…Throughout most of the study period, those reporting persistent crack use had higher viral load and poorer immune function, whereas those reporting no use had the lowest HIV-1 RNA levels and best immune health, with intermittent crack users falling in between…persistent crack use, intermittent-active, and intermittent-abstinent crack use were significantly associated with HIV disease progression, controlling for adherent HAART use, problem drinking, women’s sociodemographic characteristics, study site, illness duration, baseline viral load (in the CD4 model), and baseline CD4 cell count (in the viral load model). Persistent problem drinking was positively associated with disease progression defined by high viral load but not low CD4 cell count. In both models, adherent HAART use was protective against disease progression [an invalid statement, they can show an association, but this implies causation]…We found that the median reduction in HIV-1 RNA level was highest in non-users, at 1.7 log10 copies/µl, compared with 1.4 log10 copies/µl in inactive crack users and 1.0 log10 copies/µl in active users. The median CD4 cell count increase was highest in non-users, at 161 cells/µl, compared with 123 cells/µl in inactive users, and 100 cells/µl in active users. ”
    Cook JA et al. Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women. AIDS. 2008 Jul 11;22(11):1355-63.
    “self-report of past substance abuse was significantly greater for cocaine and heroin use in the co-infected [Hepatitis C and HIV] than in the mono-infected [HIV only] group [i.e. 90% of the co-infected group had used cocaine, versus 59.6% in the mono-infected group and 35% had used Heroin, versus 12.8%. All other rates except cannabis were higher, but not statistically significant]…prior to antiretroviral therapy, HCV+/HIV+ co-infected participants [almost all previous cocaine abusers] had significantly poorer visual memory and manual dexterity than did the HIV+ mono-infected participants.”
    Parsons TD et al. Neurocognitive functioning and HAART in HIV and hepatitis C virus co-infection. AIDS. 2006 Aug 1;20(12):1591-5.
    “The consumption of some drugs has been proved to be a risk factor that alters the normal immune function, and could be involved in the lack of immunological response in patients treated with HAART…[in this study] A total of 176 patients (61%) had acquired HIV-1 infection through intravenous drug use. These individuals had a significantly worse CD4 [immune] cell count recovery, which remained significantly different through all the study period…In our series, intravenous drug use and not HCV [Hepatitis C virus] co-infection determined the amount and speed of the increase in CD4 cells counts…The relationship between illicit drug use and the immune system has previously been established and supports our findings. Opiates and cocaine can suppress the functional activities of human peripheral blood mononuclear cells, which are known to play a key role in host defence against intracellular opportunistic pathogens…In summary, a long-term poorer increase in the CD4 cell count despite a successful virological suppression is more frequently observed in naive HIV-1-infected patients who acquired their infection by injecting drug use.”
    Dronda F et al. CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected patients: the role of intravenous drug use. AIDS. 2004;18(16):2210-2.
    “In the bivariate analysis, factors positively associated with HIV seroconversion included: injecting cocaine at least weekly, borrowing used needles [although Table 1 shows that this is negatively associated with HIV seroconversion!], incarceration, unstable housing, methadone maintenance treatment, more than 20 lifetime sex partners, and receiving payment for sex. In the multivariate analysis injecting cocaine remained the strongest predictor of HIV seroconversion [3.72 times the average risk]…The weekly use of crack cocaine was inversely associated with HIV seroincidence. Frequent heroin use was not associated with HIV seroconversion.”
    Tyndall MW et al. Intensive injection cocaine use as the primary risk factor in the Vancouver HIV-1 epidemic. AIDS. 2003 Apr 11;17(6):887-93.
    “Cocaine abuse is associated with increased rates of infections, including human immunodeficiency virus, and cocaine has immunomodulatory effects in experimental animal and cellular models…30 healthy men and women with a history of cocaine use participated in this study of neuroendocrine and immunological responses to iv injection of 0.4 mg/kg cocaine or saline placebo…Stimulation of IL-6 at 240 min was markedly reduced in subjects receiving cocaine compared with subjects receiving placebo…Because cocaine stimulates the hypothalamic-pituitary-adrenal axis, IL-6 suppression may be a consequence of corticosteroid release. Cocaine-induced suppression of proinflammatory IL-6 may mediate impaired host defenses to infections.”
    Halpern JH et al. Diminished interleukin-6 response to proinflammatory challenge in men and women after intravenous cocaine administration. J Clin Endocrinol Metab. 2003 Mar;88(3):1188-93.
    “Human alveolar macrophages (AMs) were recovered from the lungs of healthy nonsmokers (NS) or smokers of tobacco (TS), marijuana (MS), or crack cocaine (CS) and challenged in vitro with Staphylococcus aureus…AMs from MS and CS exhibited minimal antibacterial activity and failed to produce NO [Nitrous Oxide, an important signaling compound used by the immune system] unless primed with additional cytokines.”
    Shay AH et al. Impairment of antimicrobial activity and nitric oxide production in alveolar macrophages from smokers of marijuana and cocaine. J Infect Dis. 2003 Mar 15;187(4):700-4.
    “Cocaine-induced oxidative stress appears to involve decreased glutathione and lipid peroxidation, potentiating the oxidative stress associated with HIV-1 infection.”
    Shor-Posner G et al. Neuroprotection in HIV-positive drug users: implications for antioxidant therapy. J Acquir Immune Defic Syndr. 2002 Oct 1;31 Suppl 2:S84-8.
    “Controlled for confounding variables, cocaine exposure [in infants via their mother] had significant effects on cognitive development, accounting for a 6-point deficit in Bayley Mental and Motor Scales of Infant Development scores at 2 years, with cocaine-exposed children twice as likely to have significant delay (mental development index <80) (odds ratio, 1.98; 95% confidence interval, 1.21-3.24; P =.006). For motor outcomes, there were no significant cocaine effects…The 13.7% rate of mental retardation is 4.89 times higher than expected in the population at larger…Cognitive delays could not be attributed to exposure to other drugs…poorer cognitive outcomes were related to higher amounts of cocaine metabolites in infant meconium as well as to maternal self-reported measures of amount and frequency of cocaine use during pregnancy, providing further support for a teratologic model. [note that many HIV-positive infants were exposed to cocaine in-utero and their ill health and problems may be blamed on HIV, not cocaine]
    Singer LT et al. Cognitive and motor outcomes of cocaine-exposed infants. JAMA. 2002 Apr 17;287(15):1952-60.
    [‘crack’ cocaine] produces a near-instantaneous euphoric effect…Because of this property and growning concern over the risks of HIV transmission by the IV route, smoking of crack cocaine has largely replaced other modes of recreational cocaine use…[The findings in this study] suggest that a high proportion of seeming healthy crack users have chronic alveolar [lung sac] hemorrhage [bleeding] that is clinically inapparent [i.e. coughing up blood was rarely observed]
    Baldwin GC et al. Evidence of chronic damage to the pulmonary microcirculation in habitual users of alkaloidal ("crack") cocaine. Chest. 2002 Apr;121(4):1231-8.
    “These findings suggest that a high proportion of seemingly healthy crack [cocaine] users have chronic alveolar hemorrhage [bleeding in the lung cavities where oxygen/carbon dioxide exchange takes place] that is clinically inapparent. In a larger sample of 202 healthy crack smokers from whom this volunteer sample was drawn, we previously noted a 6% prevalence of self-reported hemoptysis [coughing up blood]
    Baldwin GC et al. Evidence of chronic damage to the pulmonary microcirculation in habitual users of alkaloidal ("crack") cocaine. Chest. 2002 Apr;121(4):1231-8.
    “Multivariate analysis of the female participants’ practices revealed injecting cocaine once or more per day compared with injecting less than once per day [increased the risk by 2.6 times]…of time to HIV seroconversion. Among male participants, injecting cocaine once or more per day [increased the risk by 3.3 times]…of HIV infection.”
    Spittal PM et al. Risk factors for elevated HIV incidence rates among female injection drug users in Vancouver. CMAJ. 2002 Apr 2;166(7):894-9.
    “Of the 1911 subjects [attending a sexually transmitted disease clinic] who denied having high-risk behaviors (male homosexuality, intravenous drug use, or sexual contact with high-risk persons), crack cocaine and HIV infection were associated with an odds ratio of 10.6:1 for women and 3.3:1 for men. This relationship is supported by other epidemiologic studies and by reports suggesting that cocaine depresses the immune system both in vivo and in vitro [but, of course, cocaine can’t actually cause immune deficiency by itself, it can only be a lowly handmaiden to HIV, which is really responsible for all immune deficiency]
    Roth MD et al. Cocaine Enhances Human Immunodeficiency Virus Replication in a Model of Severe Combined Immunodeficient Mice Implanted with Human Peripheral Blood Leukocytes. J Infect Dis. 2002 Mar 1;185(5):701-5.
    “Use of cocaine (rather than heroin) was independently associated with HIV prevalence among men [IV drug users in Montreal]
    Bruneau J et al. Sex-specific determinants of HIV infection among injection drug users in Montreal. CMAJ. 2001 Mar 20;164(6):767-73.
    “The exact mechanisms by which cocaine facilitates this disease [AIDS] are yet to be proven, but likely include a combination of increased risk due to cocaine-related social behaviours, a wide-ranging capacity for cocaine to suppress the immune system, and an effect of cocaine on the infectivity and replication of HIV…both human and animal studies document that cocaine alters the function of natural killer (NK) cells, T cells, neutrophils and macrophages, and alters the ability of these cells to secrete immunoregulatory cytokines.”
    Baldwin GC, Roth MD, Tashkin DP. Acute and chronic effects of cocaine on the immune system and the possible link to AIDS. J Neuroimmunol. 1998 Mar 15;83(1-2):133-8.
    “Use of marijuana and cocaine is on the rise in the United States. Although pulmonary toxicity from these drugs has occasionally been reported, little is known about their effects on the lung microenvironment. We evaluated the function of alveolar macrophages (AMs) recovered from the lungs of nonsmokers and habitual smokers of either tobacco, marijuana, or crack cocaine…These findings indicate that habitual exposure of the lung to either marijuana or cocaine impairs the function and/or cytokine production of AMs. The ultimate outcome of these effects may be an enhanced susceptibility to infectious disease, cancer, and AIDS.”
    Baldwin GC et al. Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am J Respir Crit Care Med. 1997 Nov;156(5):1606-13.
    “In the present study, we evaluated the capacity of cocaine to modify lymphocyte [white blood cells important in the immune system] cytokine production. Cocaine abrogated the IL[Inter-Leukin]-2-stimulated production of IFN-gamma and IL-8 by PBL [peripheral blood lymphocytes]…Both IL-8 and IFN-gamma are important mediators of the inflammatory response. A decrement in production of these cytokines by activated lymphocytes may significantly limit immune responses at multiple levels, resulting in an increased susceptibility to infection and malignancy.”
    Mao JT et al. Cocaine down-regulates IL-2-induced peripheral blood lymphocyte IL-8 and IFN-gamma production. Cell Immunol. 1996 Sep 15;172(2):217-23.
    “ROI [Reactive Oxygen Intermediates] and RNI [Reactive Nitrogen Intermediates] are highly reactive molecules, which kill most ingested extracellular or intracellular microbes. Thus both products provide strong protection from pathogens…we treated macrophages with different concentrations of cocaine for 45, 90 and 150 min. intervals. The results show that cocaine could inhibit the production of superoxide and hydrogen peroxide…This inhibition was correlated with the rate of ROI production”
    Shen HM et al. Suppression of macrophage reactive intermediates by cocaine. Int J Immunopharmacol. 1995 May;17(5):419-23.
    [Table 4 shows that regular crack users are 2.3 times more likely to be HIV+ than the entire group studied, the likelihood increases from no more likely with no more than 1 year smoking crack regularly to 2.1 times more likely with 6 or more years regular smoking, and to 4.7 times for those who participated in homosexual anal intercourse. The possibility that exposure to amyl nitrites, semen or crack could directly stimulate the production of antibodies is not even considered]
    Edlin BR et al. Intersecting epidemics: crack cocaine use and HIV infection among inner-city young adults. N Engl J Med. 1994 Nov 24;331(21):1422-7.
    “Cocaine is reported to be immunotoxic…Our experimental data confirm that exposure of normal human T cells to micromolar concentrations of cocaine modulates T-cell responses to stimulation by a variety of stimuli, and indicate that cocaine impairs early activation events during CD4+ but not CD4- T-cell stimulation…Our data support the proposition that cocaine abuse may place cocaine-abuser HIV-seropositive individuals at increased risk of opportunistic infections [but the experiments used blood cells from HIV-negative, healthy people, so presumably apply to people regardless of their HIV status]
    Chiappelli F et al. Cocaine blunts human CD4+ cell activation. Immunopharmacology. 1994 Nov-Dec;28(3):233-40.
    “The adjusted HR [hazard ratio] for seroconversion [becoming HIV-positive] associated with five or more sexual partners in the previous year was significantly elevated (HR=3.4 [i.e. 3.4 times higher than the average rate]). Current intravenous cocaine use (HR 2.5) and (marginally) crack [cocaine] use (HR=3.2) were associated with risk of seroconversion, but intravenous heroin and amphetamine use were not…Sharing needles and bleach use were not associated with seroconversion…When we examined the principal risk factors separately by sex, the HR associated with crack use, number of sexual partners and intravenous cocaine use were very large among female subjects”
    Moss AR et al. HIV seroconversion in intravenous drug users in San Francisco, 1985-1990. AIDS. 1994 Feb;8(2):223-31.
    “The biologic effects of substances of abuse, especially their modulation of the immune system, may significantly contribute to the outcome of an infection.”
    Bagasra O, Pomerantz RJ. Human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells in the presence of cocaine. J Infect Dis. 1993 Dec;168(5):1157-64.
    “one third of the 43 women [from Florida] who had used crack cocaine were infected [HIV seropositive][and] were seven times more likely to be positive for gonorrhea and five times more likely to be positive for syphilis than those who reported never having used crack cocaine…the five independent predictors of HIV infection in these women were having used crack cocaine [3.3 times higher than those not in this group], having had more than two sexual partners [4.6 times], being black but neither Hispanic nor Haitian [11 times], having had sexual intercourse with a high-risk partner [5.6 times], and testing positive for syphilis in the prenatal examination [3.1 times]
    Ellerbrock TV et al. Heterosexually transmitted human immunodeficiency virus infection among pregnant women in a rural Florida community. N Engl J Med. 1992 Dec 10;327(24):1704-9.
    “The seroprevalence in [crack cocaine using] individuals denying [male-to-male sexual contact, intravenous drug use and heterosexual contact with an intravenous drug user] was 3.6% (50 out of 1389) and 4.2% (22 out of 522) in men and women, respectively.”
    Chiasson MA et al. Heterosexual transmission of HIV-1 associated with the use of smokable free-base cocaine (crack). AIDS. 1991 Sep;5(9):1121-6.
    “The HIV-1 seroprevalence of the study participants [patients at a STD clinic in the South Bronx] was 12% (369 out of 3084) and was the same for both men and women…Demographic characteristics, sexual and non-intravenous drug using behaviors were examined in more detail for the 50 seropositive men and the 22 seropositive women who denied traditional risk behavior for HIV-1 infection…13(59%) of the women were crack [smokable, freebase cocaine] users…Among the men, 24% reported crack use. The overall seroprevalence among the 201 crack users, who denied traditional HIV associated risk behaviors, was 12%”
    Chiasson MA et al. Heterosexual transmission of HIV-1 associated with the use of smokable free-base cocaine (crack). AIDS. 1991 Sep;5(9):1121-6.
    “The majority [23/36] of HIV-infected individuals denied usual risk factors for HIV…HIV infection was associated with female sex, crack cocaine use, GUD [genito-urinary disease] and multiple concurrent STDs.”
    Chirgwin K et al. HIV infection, genital ulcer disease, and crack cocaine use among patients attending a clinic for sexually transmitted diseases. Am J Public Health. 1991;81(12):1576-9.
    “the process [of ‘free-basing’ cocaine to inhale it] entails subjecting a white powder containing cocaine hydrochloride and other substances, ranging from lactose and procaine amid to cellulose and other poorly characterized solvents [often ether] and diluents, to a procedure by which the material is converted to an alkaloid form of cocaine…”free-base”.”
    Lerner WD. Cocaine abuse and acquired immunodeficiency syndrome: a tale of two epidemics. Am J Med. 1989 Dec;87(6):661-3.
    “Our experiments show that cocaine has a general suppressive effect on the mouse immune system…Injections of 5 mg/kg of cocaine 24hr before assay suppressed the number of thymocytes but the effect was not observed 48, 72, and 96 hr after injections. However, at higher doses, the suppressive effects on thymocytes were not entirely recovered 96 hr after injection…The size of two different tumors appeared to increase in cocaine-treated mice”
    Ou DW, Shen ML, Luo YD. Effects of cocaine on the immune system of Balb/C mice. Clin Immunol Immunopathol. 1989 Aug;52(2):305-12.
    [Subjects in this study were in public methadone treatment for heroin or cocaine addiction in 1986 and 1987] A strong association was found between [HIV] seropositivity and current or prior cocaine injection. The odds ratio for current monthly cocaine injection compared with no cocaine use was 2.2 and rose to 2.6 for weekly cocaine injection and to 6.4 for daily cocaine injection. Conversely, the frequency of current heroin injection was only weakly associated with HIV infection, with no increased risk for monthly use and only slightly increased risk for daily heroin injection compared with no current heroin use…no subject had regularly used cocaine prior to 1984…Intravenous cocaine use has increased dramatically in the last decade…cocaine injectors had a higher prevalence of HIV infection whether they used cocaine alone, cocaine and heroin separately, or cocaine and heroin mixed together.”
    Chaisson RE et al. Cocaine use and HIV infection in intravenous drug users in San Francisco. JAMA. 1989 Jan 27;261(4):561-5.
    “The interviews confirmed an association between intravenous drug use and HIV seropositivity [16/35 taking drugs only intravenously], surprisingly, however, the results also indicated a significant relation between non-intravenous use of cocaine and crack and seropositivity [84% taking cocaine and crack other than intravenously]
    Sterk C. Cocaine and HIV seropositivity. Lancet. 1988 May 7;331(8593):1052-3.
    “Patients [with Kaposi’s Sarcoma] reported significantly longer histories of ever having been exposed to chemicals or solvents at work (risk ratio = 7.5) [compared to matched patients without KS]...self-reports of ever having used various recreational drugs, including amyl nitrite, ethyl chloride, cocaine, phencyclidine (‘angel dust’), methaqualone, and amphetamines…[were each] associated with a risk ratio of 4 or greater [i.e. patients with KS were at least 4 times more likely to have used each of these drugs, than those without]...Significant dose-response relationships were found for amphetamines, amyl nitrite, cocaine, and ethyl chloride”
    Marmor M et al. Risk factors for Kaposi’s Sarcoma in homosexual men. Lancet. 1982 May 15;1:1083-6.

    General Health Risks of Recreational Drugs

    Some research indicates that a variety of types of drugs (and mode of use) have significant health risks. The question is whether the association with HIV indicates that the drugs, or HIV, or a combination, causes the observed poor health of many drug users.

    “A group of HIV-positive youth studied between 1999 and 2000 reported having more sexual partners, more unprotected sex and more drug use than HIV-positive youth studied between 1994 and 1996, say Marguerita Lightfoot, Ph.D. and colleagues at the UCLA AIDS Institute at the David Geffen School of Medicine.”
    Ham B. Youth with HIV take more risks after new meds introduced. Health Behavior News Service. 2005 Feb 28
    http://www.cfah.org/hbns/getDocument.cfm?documentID=1026
    “A cohort of 19 patients with evidence of nonprogressive HIV-1 infection [i.e. no AIDS-defining illnesses] was established in 1997 at our institution…in Madrid. All patients had serologically proven HIV-1 infection for at least 10 years, repeated CD4 cell counts >500 million cells/l, and no prior history of HIV-related symptoms, in the absence of any antiretroviral therapy. Most of these individuals had been exposed to HIV-1 before 1985 or 1987, when they first tested positive for HIV-1 antibodies. One subject was known to be HIV-1 seropositive since 1979, after testing retrospectively sera stored from that time…All but one were former injecting drug users [indicating that drug use might have stimulated 'HIV' antibodies, but stopping drug use had also prevented their health from declining to 'AIDS']
    Rodes B et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. AIDS. 2004 May 21;18(8):1109-16.
    “In HIV/AIDS patients, perturbations in the antioxidant defense system, including changes in levels of antioxidant micronutrients, have been observed in plasma as well as in various tissues, particularly in…drug users. Moreover, addictive drugs of abuse have been shown to produce significant nutritional alterations that can contribute to the cognitive changes observed in HIV-1-infected persons”
    Shor-Posner G et al. Neuroprotection in HIV-positive drug users: implications for antioxidant therapy. J Acquir Immune Defic Syndr. 2002 Oct 1;31 Suppl 2:S84-8.
    “in 1989 Kreek reported in the Journal of Pharmacology and Experimental Therapeutics that 11 long-term heroin users had a mean of 1500 CD4s - a significant elevation from the norm and the oppositive of what is seen in AIDS. "Heroin is a blessedly untoxic drug." concludes Kreek”
    Cohen J. Could Drugs, Rather Than a Virus, Be the Cause of AIDS?. Science. 1994 Dec 9;266:1649.

    IV Drug Abuse

    IV drug abuse is certainly associated with AIDS, but it is also associated with a number of health conditions related to a combination of the direct effects of the drugs, substances used to 'cut' the drugs and the living conditions of drug users - poor nutrition and sanitation, often homeless and so forth. Drug addicts have always had serious health problems, often associated with immune suppression, such as Tuberculosis. Can HIV now be blamed for some or all of these problems?

    “The study was conducted with non-governmental organizations (NGOs) in three locations with high concentrations of IDU [intravenous drug users]: Kiev, Odessa and Makeevka/ Donetsk [in the Ukraine]…891 individuals were recruited…In order to provide a valid assessment of variables associated with HIV status, we omitted from further analyses the 113 participants who were aware that they were HIV positive prior to entering the study [leaving 778]…those who were HIV positive were significantly older and had been injecting longer than those who were HIV negative…Females were more likely to be HIV positive as were those who had been arrested. Having had syphilis, hepatitis B or hepatitis C was associated with HIV infection. Sedative/opiate mixture was the only drug type predictive of HIV. Daily injecting was associated with being HIV positive, as was front/back loading with a dealer. Using a previously used syringe was not associated with HIV infection. With regard to sexual risk behaviors, those who were abstinent were more likely to be HIV positive than those who were sexually active. Those who had an HIV-positive sex partner, however, were twice as likely to be HIV positive themselves as those who did not have an HIV-positive partner or who did not know the status of their partner…we were somewhat surprised to find that using a used needle was not related to HIV status.”
    Booth RE et al. Predictors of HIV sero-status among drug injectors at three Ukraine sites. AIDS. 2006 Nov 14;20(17):2217-23.
    “The strongest predictor of anaemia was frequency of injecting drugs. Less than half the study population (41%) injected more than 10 times per month, whereas 84% of the people in this group had anaemia”
    van der Werf MJ et al. Prevalence, incidence and risk factors of anaemia in HIV-positive and HIV-negative drug users. Addiction. 2000 Mar;95(3):383-92.
    “the mean duration of drug use preceding the first registered admission [to this Swiss hospital] was 6.7 years [unconfirmed HIV-negative], 7.1 years [confirmed negative] and 11.3 years [HIV-positive]
    Scheidegger C, Zimmerli W. Incidence and spectrum of severe medical complications among hospitalised HIV-seronegative and HIV-seropositive narcotic drug users. AIDS. 1996 Oct;10(12):1407-14.
    “More than 15% of the HIV-1-seropositive [IV-drug-using] individuals had plasma vitamin A levels less than 1.05 micromol/L, a level consistent with vitamin A deficiency.”
    Semba RD et al. Increased Mortality Associated with Vitamin A Deficiency During HIV 1 Infection. Arch Intern Med. 1993 Sep 27;153:2149-54.
    “CD4 cell counts and percentages were obtained from 1,246 HIV-seronegative [IV drug using] subjects…9 had at least one CD4 cell count of <300 cells/microliter or a CD4[:CD8 ratio] <20%...4 subjects had CD4 counts <300 cells/microliter or CD4 < 20% for two points in time, meeting the current surveillance definition for ICL [HIV-free AIDS]...We also examined the data for the 21 subjects who had one CD4 count between 300 and 500 cells/microliter and for whom there was at least one follow-up data collection. None of these subjects progressed to a CD4 cell count of <300 cells/microliter or a CD4<20% at any follow-up visit. Five of these 21 subjects later seroconverted for HIV [indicating that low CD4 cell counts preceded infection, and could not have been caused by HIV]
    Des Jarlais DC et al. CD4 lymphocytopenia among injecting drug users in New York City. J Acquir Immune Defic Syndr. 1993;6(7):820-2.
    “Human immunodeficiency virus (HIV) prevalence was studied in an unselected group of 216 female and transsexual prostitutes…All 128 females who did not admit to drug abuse were seronegative; 2 of the 52 females (3.8%) who admitted to intravenous drug abuse were seropositive.”
    Modan B et al. Prevalence of HIV antibodies in transsexual and female prostitutes. Am J Public Health. 1992 Apr;82(4):590-2.
    “Intravenous drug abusers appear to be at special risk of acquiring tuberculosis, and a high rate of infection in this group was reported well before AIDS began.”
    Goldman KP. AIDS and tuberculosis. BMJ. 1987;295:511-2.
    “The best single predictor of seropositivity at the start of the follow-up period was the frequency of drug injection 2 to 5 years prior”
    Des Jarlais DC et al. Development of AIDS, HIV seroconversion and potential cofactors for T4 cell loss in a cohort of intravenous drug users. AIDS. 1987;1:105-11.

    Mothers, Drugs, HIV and AIDS

    Drug use by mothers has long been associated with ill health in both the mothers and their babies. Why do we now need HIV to explain these illnesses?

    “survival curves also revealed a significantly faster rate of disease progression for infants born to women with a history of IDU [IV drug use]
    Abrams EJ et al. Maternal health factors and early pediatric antiretroviral therapy influence the rate of perinatal HIV-1 disease progression in children. AIDS. 2003 Apr 11;17(6):867-877.
    “Risk exposures for HIV infection among the mothers of the 6750 [US] children with perinatally acquired AIDS included injecting-drug use (IDU) (41%), sexual contact with a partner with or at risk for HIV/AIDS (34%) [probably IV drug users, with a high probability that the mother is also a drug user, although not necessarily by injection]
    CDC. AIDS among children -- United States, 1996. MMWR. 1996 Nov 22;45(46):1005-10.
    www.cdc.gov/epo/mmwr/preview/mmwrhtml/00044515.htm
    “Postnatal mortality in infants of HIV-infected mothers followed up from birth was increased 15-fold over the general population with a very high incidence (2 in 100) of sudden infant death syndrome apparently unrelated to HIV infection [but]...Intravenous drug use (IVDU) was reported...for 68% of mothers; 46% of them were reported to have used drugs during pregnancy...Neonatal signs of drug withdrawal were seen in 19% of the infants [could this be why their babies were sicker?]
    Kind C et al. Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study. Eur J Pediatr. 1992;151:442-8.
    “Separate analysis of the infants according to maternal risk factors showed that maternal drug addiction was associated with some abnormalities but that the association may be independent of HIV infection. Below-normal height and weight at birth and a higher rate of malformations, notably facial, have been reported in several studies of the infants of drug-addicted mothers, even before the HIV epidemic…The high incidence of unexplained sudden death reported in this study can also be attributed to maternal drug addiction…10 infants had morphological anomalies, including a labiopalatal cleft in 4 cases. 9 of the 10 children were born to drug-addicted mothers”
    Blanche S et al. A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. N Engl J Med. 1989 Jun 22;320(25):1643-8.
    “Until 1985, the majority of mothers of children with AIDS seen in our clinic acquired their HIV infection through intravenous drug abuse and/or promiscuity. At present being a sexual partner of a male at risk for AIDS is the only risk factor in a large percentage of mothers of our paediatric AIDS patients [and if this men are IV drug users, it's quite likely that the women are non-IV drug users, e.g. of crack cocaine]…an AIDS embryopathy [malformed fetus] has been observed. The characteristic features…are microcephaly [small head] and a group of craniofacial dysmorphic [malformed skull and face] features including frontal bossing [swelling], hypertelorism [eyes abnormally far apart], flattened nasal bridge, obliquity of the eyes, blue sclerae and patulous [spreading] lips [incredibly there is no consideration that these features might be due to maternal drug abuse].”
    Novick BE, Rubinstein A. AIDS--the paediatric perspective. AIDS. 1987 May;1(1):3-7.
    “We have studied 27 children aged 1 day to 42 months and at risk for acquired immunodeficiency syndrome (AIDS). Except 1 who had been transfused, all had drug-addict mothers”
    Gaetano C et al. Delayed and defective anti-HIV IgM response in infants. Lancet. 1987 Mar 14;1(8533):631.

    Needle Exchange Programs

    Everyone knows that Needle Exchange Programs (NEP) will stop the spread of HIV, and reduce the incidence of AIDS. But, this information indicates that perhaps 'everyone' is wrong.

    “The study was conducted with non-governmental organizations (NGOs) in three locations with high concentrations of IDU [intravenous drug users]: Kiev, Odessa and Makeevka/ Donetsk [in the Ukraine]…Using a previously used syringe was not associated with HIV infection”
    Booth RE et al. Predictors of HIV sero-status among drug injectors at three Ukraine sites. AIDS. 2006 Nov 14;20(17):2217-23.
    “The HIV incidence among drug users in the ACS has declined since 1985. Accompanied by a reduction in injecting drug use and needle sharing, this decline occurred despite continued sexual risk behaviour.”
    Lindenburg CE et al. Decline in HIV incidence and injecting, but not in sexual risk behaviour, seen in drug users in Amsterdam: a 19-year prospective cohort study. AIDS. 2006 Aug 22;20(13):1771-1775.
    “Of 1,315 participants…11.0% reported NEP attendance but did not attend, and 2.2% reported not attending NEP but did attend…persons who overreported NEP [Needle Exchange Program] attendance were more likely to have injected frequently (adjusted odds ratio (AOR) = 1.29), denied needle sharing (AOR = 0.69), and been an HIV seroconverter (AOR = 1.83).”
    Safaeian M et al. Validity of self-reported needle exchange attendance among injection drug users: implications for program evaluation [Correction in 155:582]. Am J Epidemiol. 2002 Jan 15;155(2):169-75,582.
    http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/155/2/169.pdf
    “In this study, sharing syringes in the past 6 months was negatively [!] associated with HIV prevalence among both sexes…After adjustment for other factors, male injection drug users who had shared syringes in the previous 6 months were at lower risk of being HIV positive [61% of the risk of those who had not shared]
    Bruneau J et al. Sex-specific determinants of HIV infection among injection drug users in Montreal. CMAJ. 2001 Mar 20;164(6):767-73.
    “Needle exchange is one of the few interventions available, and a context-specific approach to its use seems to be the responsible way to proceed [translation: Often the programs don’t reduce the rate of HIV transmission, or even increase it, but doing nothing would be a worse sin than doing something counterproductive!]
    Moss AR. “For God’s Sake, Don’t Show This Letter to the President...”. Am J Public Health. 2000 Sep;90(9):1395-6.
    “Syringes supplied by SEPs [syringe exchange programs] account for fewer than 2% of those needed to meet the standard of 1 syringe per injection.…syringes with either 2 or 20 microliters of blood [containing HIV-negative blood mixed with the supernatant of an HIV culture to simulate 0.1 to 5 infectious units per microliter] stored at 4C yielded viable HIV-1 even at 42 days of storage, the longest duration tested. At the other extreme, at 37C, syringes with either 2 or 20 microliters of blood failed to yield viable HIV-1 if stored for 7 days or longer. At 22C [room temperature], viable HIV-1 was recovered from some syringes with approximately 2 and 20 microliters of blood for up to 21 and 42 days, respectively. At both 27C and 32C, viable HIV-1 was receovered from some syringes with approximately 2 and 20 microliters of blood for 1 and 7 days, respectively.”
    Heimer R, Abdala N. Viability of HIV-1 in syringes: implications for interventions among injection drug users. AIDS Read. 2000 Jul;10(7):410-7.
    “Injection drug users (IDU) constitute the major risk group for HIV infection in many countries world- wide. IDU are at risk of HIV infection through unsafe injecting practices and risky sexual behaviour [no reference given]...[but]...As previously found in this cohort, the study results demonstrated an increased risk of HIV infection associated with NEP use: inconsistent NEP users had a higher risk than consistent users when compared with non-users. However, we chose to exclude this variable”
    Brogly SB et al. Risk behaviour change and HIV infection among injection drug users in Montreal. AIDS. 2000;14:2575-2582.
    “Of 694 subjects [IV drug users in Vancouver], the 15-month cumulative HIV incidence [number of people changing from HIV-negative to HIV-positive] was significantly elevated in frequent NEP attendees (11.8 ± 1.7 versus 6.2 ± 1.5%).”
    Schechter MT et al. Do needle exchange programmes increase the spread of HIV among injection drug users?: An investigation of the Vancouver outbreak. AIDS. 1999;13(6):F45-51.
    “The authors utilized a cohort study among Seattle injection drug users (IDUs) to assess whether participation in a syringe exchange program was associated with incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection…There was no apparent protective effect of syringe exchange against HBV (former exchange users, relative risk (RR) = 0.68, 95% confidence interval (CI) 0.2-2.5; sporadic exchange users, RR = 2.4, 95% CI 0.9-6.5; regular users, RR = 1.81, 95% CI 0.7-4.8; vs. RR = 1.0 for nonusers of the exchange; adjusted for daily drug injection). Neither did the exchange protect against HCV infection (sporadic users, RR = 2.6, 95% CI 0.8-8.5; regular users, RR = 1.3, 95% CI 0.8-2.2; vs. RR = 1.0 for nonusers; adjusted for recent onset of injection and syringe sharing prior to enrollment). [In other words regular needle exchange users were 1.8 times more likely to be Hepatitis B positive than non-users, and 1.3 times more likely to be Hepatitis C positive]
    Hagan H et al. Syringe exchange and risk of infection with hepatitis B and C viruses. Am J Epidemiol. 1999 Feb;149(3):203-13.
    [Table 5 shows that the risk of an IV drug user becoming HIV-positive is 10.2 to 22.9 times greater among consistent needle exchange program users versus non-users. Frequent users were 2.2 to 3.9 times more likely and infrequent users had about the same risk as non-users.]
    Bruneau J et al. High rates of HIV infection. Am J Epidemiol. 1997 Dec 15;146(12):994-1002.
    “The HIV epidemic raging in the heart of Vancouver is now considered to be the most rampant in the developed world…the epidemic…has occurred despite Vancouver’s celebrated needle exchange program. More than two million needles are exchanged each year in the program, which started in 1988”
    Munro M. AIDS explodes in Vancouver. Calgary Herald. 1997 Oct 3
    “HIV-positive IDU were significantly more likely to be established IDU [>2 yrs]…HIV-positive IDU were more likely to have ever attended NEP, and to attend NEP on a more regular basis, compared with HIV-negative IDU”
    Strathdee SA et al. Needle exchange is not enough: lessons from the Vancouver injecting drug use study. AIDS. 1997 Jul 11;11(8):F60-5.
    “Current intravenous cocaine use (HR 2.5) and (marginally) crack [cocaine] use (HR=3.2) were associated with risk of seroconversion, but intravenous heroin and amphetamine use were not…Sharing needles and bleach use were not associated with seroconversion”
    Moss AR et al. HIV seroconversion in intravenous drug users in San Francisco, 1985-1990. AIDS. 1994 Feb;8(2):223-31.

    Nitrite Inhalants

    Nitrite inhalants are little known outside the gay male community. They are heavily (and very cynically) marketed to this community. It is known that they are carcinogenic and immune suppressive. So how could they possibly have anything to do with an Acquired Immune Deficiency Syndrome?

    “My partner was diagnosed as HIV+, with a CD Count of 97 on Monday this week. The reason for us checking was that every two (2) years or so he would lose weight, followed by mouth sores and have a general feeling of no energy and not wanting to eat. We have been a couple for 15 years and this has been going on for some 8 years…Each time this happenned we administered protein suppliments, high doses of vitamins and minerals, proper diet (45% protein / 45% carbs / 10% fat) + feet reflexology. It took about 2 - 4 weeks for his weight to build and be back to his "normal" self. Back to gym and training...great sense of wellness - no winter colds and flu etc. When he was diagnosed with HIV this week, I naturally believed I would be HIV+ ... it just could not be any different given the wide information relating to transmission. I under went tests (in fact three different types were performed - not sure exactly what), but am negative. Because of this I went to another Doctor and was again tested - doing different tests, and the tests came back negative. [In Summary] 1. My partner has clearly been positive and showing signs for some 8 years and yet each time he got sick, we nursed him back to health without any medication; 2. The common factor each and every time he showed these signs of weight losss and sores was ALWAYS after recreational drug use - when recreational drugs were not in use, there were no problems with his health; 3. Being Gay partners for 15 years, we naturally enagaged in sexual activity (unprotected) and over the years come into contact with each other bodily fluids…[Questions] a. How after all these years could I not be HIV+?; b. Why does his so called CD count only drop after recreational drug use - and when the symptoms showed, we simply followed common sense with proper eating and suppliments, and he recovered. He never ever suffered from weight loss or sores or any other typical OI's any other time.”
    [Name withheld]. Letter to David Crowe. Personal Correspondence. 2009 Feb 21
    “Poppers are immunosuppressive. Immunosuppression may increase susceptibility to HIV and HHV-8 infection. [this website includes extensive scientific literature references on the topic of poppers (nitrite inhalants)]
    Wilson H. Poppers information and poppers research. poppers.cfsites.org. 2007 Dec [accessed]
    http://poppers.cfsites.org/
    “Doses of amyl nitrite, known on the street as poppers, are sold under the counter at some sex shops in Montreal and other major cities. They're ingested [probably should be ‘inhaled’] on the gay and straight party scenes, often in combination with other drugs such as ecstasy…Health Canada said it's looking into reports that poppers, sold under brand names such as Rush and Locker Room, have increased in popularity after falling out of favour in the 1990s…The combination of poppers and ecstasy, another popular party drug, could be deadly, according to a San Francisco study presented in 2001 at a Centers for Disease Control conference in Atlanta…poppers could harm people with pre-existing heart problems or a susceptibility to brain aneurysms…Poppers occupy a grey zone in Canadian law - it's illegal to sell them as aphrodisiacs, so they're marketed instead as leather cleansers, video-cassette cleaners and even incense…JustPleasure.com [in Vancouver] sells poppers for prices ranging from $10.95 to $19.95 per bottle. Carole MacFadden, director of sales and marketing, said demand for the drugs shot through the roof as soon as her firm was launched last year…MacFadden denied her company was breaking any laws by selling poppers, explaining the product doesn't appear on her website and is only sold to those who specifically request it…the drug's hallucinogenic effects impair a user's judgment, making the person more likely to take dangerous sexual risks that expose them to sexually transmitted diseases such as HIV [or perhaps directly causes AIDS diseases].”
    Daly B. Club scene’s deadly new aphrodisiac: Amyl nitrate being inhaled from bottles. Canadian Press. 2003 Oct 5
    “The prevalence of reported unprotected anal intercourse (UAI) increased from 37% to 50% between 1993 & 1994 and 1996 & 1997. Almost half of all men who reported UAI in 1996 & 1997 indicated that it occurred with a partner of unknown or discordant HIV antibody status. This high-risk practice correlated with greater numbers of male sex partners, use of nitrite inhalants, sex in commercial sex environments, perceived difficulty controlling sexual risk-taking, and negative emotional reactions.”
    Ekstrand ML et al. Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status. AIDS. 1999 Aug 20;13:1525-33.
    “Men were coded as ‘high transmission risk’ if they reported UAI with a partner of different or unknown HIV status, as ‘low transmission risk’ if they reported all UAI partners to be seroconcordant, and as ‘no risk’ if they reported no UAI at all…Three variables, i.e. greater frequency of sex, any use of nitrite inhalant drugs in the previous 12 months, and difficulty avoiding sexual risks, differentiated membership in the ‘high transmission risk’ group from the ‘no transmission risk’ men in multivariate analyses.”
    Ekstrand ML et al. Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status. AIDS. 1999 Aug 20;13:1525-33.
    “Groups of mice were exposed in an inhalation chamber to 900 ppm isobutyl nitrite ['poppers'] for 45 minutes per day for 14 days and then assayed for immune reactivity. The T-dependent antibody responses of nitrite treated mice were reduced by 50-65%…Cytotoxic T cell (CTL) induction was reduced by 40%…and the tumoricidal activity of peritoneal exudate macrophages [cells] was reduced by 40%…[in a later experiment] inhalant exposure increased the tumor incidence from 21% of control mice to 75% of inhalant exposed mice…the rate of increase in mean tumor weight was nearly 4-fold faster in nitrite exposed mice.”
    Soderberg LSF. Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Toxicology Letters. 1999 Jan 11;104(1-2):35-41.
    “In 1995, 3,553 repeat anonymous HIV tests were performed among men who have sex with men in San Francisco…A total of 2,822 subjects met all inclusion criteria. A seroconverter was defined as a person who reported a prior HIV-negative test and whose current test was HIV positive…6 variables were significantly associated with increased HIV seroincidence in multivariate analysis: African-American ethnicity, age under 36, sex with an HIV-positive person, 10 or more sex partners, unprotected receptive anal sex, and use of the drug amyl nitrate ('poppers') during sex…Injection drug use was not associated with a significant increase in HIV seroconversion…a history of sexually transmitted disease did not appear to contribute an increased risk of seroconversion after controlling for markers of high risk sexual behavior”
    McFarland W et al. Estimation of human immunodeficiency virus (HIV) seroincidence among repeat anonymous testers in San Francisco. Am J Epidemiol. 1997 Oct 15;146(8):662-4.
    http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/146/8/662.pdf
    “The epidemiology of nitrite inhalant use fits well with epidemiologic AIDS-related KS [Kaposi’s Sarcoma] data. Nitrite inhalants are used more commonly by men who have sex with men than others; use has been declining since AIDS was reported and has roughly paralleled the reported pattern of KS cases, and use among whites is greater than among African- Americans, as is the incidence of KS. Some but not all epidemiologic studies have shown a statistical association between the development of KS among men who have sex with men with AIDS and the use of large quantities of nitrite inhalants when compared with gay men with AIDS but without KS. In addition, nitrites act on blood vessels, the site of KS, and are known to be mutagenic.”
    Haverkos HW. Is Kaposi sarcoma caused by new herpesvirus?. Biomed Pharmacother. 1996;50(6-7):318-9.
    “AIDS-related KS [Kaposi’s Sarcoma] lesions have been anecdotally reported to occur most often on the chest and face, especially the nose; those are the body areas most heavily exposed to nitrite vapors.”
    Haverkos HW, Drotman DP. NIDA technical review: nitrite inhalants. Biomed Pharmacother. 1996;50(5):228-30.
    “Noninfectious environmental agents, such as nitrite inhalants, also have been proposed to play a role in KS [Kaposi’s Sarcoma] tumorigenesis”
    Chang Y et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9.
    [the author quotes Robert Gallo as saying] [What I found reasonable was Peter Duesberg's] concept to combine virus with certain chemicals like poppers in the monkey model, because that's KS [Kaposi's Sarcoma]. KS, there is no question, is multifactoral. KS, there is no question, is enormously augmented by HIV, but clearly it's multifactoral. We've been arguing that from the beginning. We know that. You don't just take HIV and get Kaposi's sarcoma”
    Hoke F. Robert C. Gallo looks beyond NIH and defends the past. The Scientist. 1994 Nov 14;8(22):12.
    “Conclusions…(1) unprotected anogenital receptive intercourse poses the highest risk for the sexual acquisition of HIV-1 infection; … (8)the association of substance [i.e. drug] use increases the likelihood of practicing anogenital receptive intercourse [they do not consider the possibility that drug use, particularly nitrite inhalants, may be the cause of disease, and receptive anal intercourse is just an associated, not causative, factor]
    Caceres CF, van Griensven GJP. Male homosexual transmission of HIV-1. AIDS. 1994 Aug;8(8):1051-61.
    “64.7% of the 187 sexual partners [of homosexual men, some with AIDS] had a history of unprotected receptive anal intercourse over the previous 5 years. Among sexual partners of HIV-1 infected men, HIV-1 seropositivity was significantly associated with a 5-year history of unprotected receptive anal intercourse, with an HIV-1-infected [partner], a history of gonorrhea or syphilis, a history of nitrite [inhalant] use, total number of unprotected receptive anal partners over the previous 5 years, nonwhite race, and lower educational level”
    Seage GR 3rd et al. Risk of human immunodeficiency virus infection from unprotected receptive anal intercourse increases with decline in immunologic status of infected partners. Am J Epidemiol. 1993 Apr 15;137(8):899-908.
    http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/137/8/899.pdf
    “drug use information [in Schechter et al. Lancet. 1993 Mar 13, p658] was obtained on an ever-versus-never basis, rather than being quantified. But with drugs, the dose is the poison…Indeed, Schechter's data also confirm the quantitative aspect of the drug hypothesis if one considers that antibody against HIV is a marker for drug consumption, as they do ('risk behaviours are known to correlate to HIV-1 infection…'). Since it takes about 1000 drug-promoted sexual contacts to be infected with HIV, HIV antibody-positive individuals have been exposed to the drug equivalent of 1000 contacts more than those who are HIV-negative…The T-Cell [CD4+] losses that Schechter et all attribute to HIV can also be explained by zidovudine [AZT], which is prescribed to HIV-positive, but not to HIV-negative, individuals…Thus treatment with zidovudine and a higher lifetime dose of recreational drugs in positive than in negative subjects explain the decline of T-cells in HIV-positive individuals.”
    Duesberg P. HIV and the aetiology of AIDS. Lancet. 1993 Apr 10;341:957.
    “We examined factors associated with the subsequent development of AIDS-related Kaposi's sarcoma in a cohort of 353 homosexual men infected with human immunodeficiency virus (HIV)…including those related to demographics, sexual behavior, illicit drug use, and medical history. We found no strong associations between any of these variables and the development of opportunistic infection, but two were related to Kaposi's sarcoma: use of nitrite inhalants and high numbers of sexual contacts during the period 1978-1982 in the AIDS epidemic centers of San Francisco, Los Angeles, and/or New York…[these] remained independently associated with risk of Kaposi's sarcoma even after multivariate adjustment for a number of classical HIV risk factors…The effect of nitrites could be due to an independent biological mechanism [i.e. another virus] or to enhancement of transmission of the cofactor [or the sole factor, with sexual transmission just a confounding factor]
    Archibald CP et al. Evidence for a sexually transmitted cofactor for AIDS-related Kaposi's sarcoma in a cohort of homosexual men. Epidemiology. 1992 May;3(3):203-9.
    “Use of poppers was not significantly related to Kaposi’s sarcoma. Popper use was related to insertive riming: about half the men who had never used poppers or had used them less than once a month reported practising insertive rimming, whereas most (20/26) of the men who used poppers at least once a week also practised insertive rimming. Stratification of the data by insertive rimming shows that there is no trend at all in Kaposi’s sarcoma risk with frequency of popper use [but flaws in this analysis include self-reporting of drug use (usually under-reported), a control comparison with other people with other AIDS diseases rather than with the general population, an overall high usage of poppers (30 out of 65) compared to rare usage in the general population, and no estimate of the total lifetime exposure to poppers (just current usage). Only 6 people studied claimed never to have used poppers (less than 10%) and more than half used poppers more than once a month]
    Beral V et al. Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet. 1992 Mar 14;339(8794):632-5.
    “The role of nitrite [inhalants] was evaluated between 1985 and 1988 in a study of sexual transmission of the human immunodeficiency virus (HIV) among homosexual male couples in Boston, Massachusetts. Initial enrollment data suggested that a history of unprotected receptive anal intercourse and a history of nitrite use were independent risk factors for HIV infection. In addition, interaction [strong association] between nitrite use and unprotected receptive anal intercourse was observed after controlling for number of unprotected receptive anal sex partners and history of sexually transmitted diseases.”
    Seage GR et al. The relation between nitrite inhalants, unprotected receptive anal intercourse, and the risk of human immunodeficiency virus infection. Am J Epidemiol. 1992 Jan;135(1):1-11.
    http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/135/1/1.pdf
    “Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite [and note that many people lie about their sexual habits or drug use]
    Deininger S et al. Behavioral characteristics and laboratory parameters in homo- and bisexual men in West Berlin: an evaluation of five years of testing and counselling on AIDS. Klin Wochenschr. 1990;68:906-13.
    “349 homosexual or bisexual men with biopsy proven KS seen in a university hospital-based dermatology practice between 1981 and 1989 were tested for antibodies to HIV-1, and 343 were HIV-1 positive...Inhaled nitrite (poppers) use was reported by 5 [of the 6 who were HIV-1 negative].”
    Friedman-Kien AE et al. Kaposi’s Sarcoma in HIV-negative men. Lancet. 1990;335(8682):168-9.
    “Nitrite inhalants (poppers) or other substances to which homosexual men have been preferentially exposed have been suggested as a cause of Kaposi’s Sarcoma. The use of poppers is highly correlated with behaviours that provide opportunities for acquiring sexually transmitted infections. Kaposi’s sarcoma has been associated with both sexual practices and the use of poppers…The occurrence of Kaposi’s sarcoma in children and elderly people with parenterally transmitted HIV and in one-tenth of AIDS patients in Africa, where poppers are not used, suggests that poppers cannot account for the pattern of occurrence of Kaposi’s sarcoma in AIDS patients [but then, neither can homosexual practices such as rimming and fisting, which are presumably also rare in those groups!]
    Beral V et al. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?. Lancet. 1990 Jan 20;335(8682):123-8.
    “…the areas where absorbed concentrations of volatile nitrites would be expected to be highest - the skin surround the nose and in the nasal/pulmonary mucosa - are also reported to be the areas in which KS occurs in persons with AIDS. This association logically leads to the hypothesis that there is a causal relationship between nitrites and KS, perhaps mediated by the formation of N-nitroso compounds.”
    Haverkos HW, Dougherty JA. Health Hazards of Nitrite Inhalants (Preface). NIDA Research Monograph. 1988;83:vii-xi.
    “There are important reasons for considering nitrite inhalation as a factor in the development of AIDS-related KS[Kaposi’s Sarcoma] in young male homosexuals. These are (1) the pharmacologic properties of amyl, butyl and isobutyl nitrites, which are toxic; (2) the mutagenic, teratogenic and carcinogenic products resulting from metabolism of N-nitroso compounds; (3) the potent carcinogenicity of N-nitroso compounds in 39 different animal species; and (4) the deleterious effects of volatile nitrites on human lymphocytes both in vitro and in vivo…there are additional reasons for pursuing the connection between nitrite inhalation and development of KS. These include: (1) the timing of the production and sales of volatile nitrites for use as recreational drugs and the subsequent outbreak of the AIDS epidemic (7 to 10 years); (3) the extensive use of nitrities among male homosexuals; (3) the virtual universal history of nitrite use by young male homosexuals in whom KS has developed during the past 3 years; and (4) the age group in which KS is developing is consistent with a cohort initially exposed 7 to 10 years ago.”
    Newell GR, Spitz MR, Wilson MB. Nitrite Inhalants: Historical Perspective. NIDA Research Monograph. 1988;83:1-14.
    “all four butyl nitrites were found to be moderately toxic compounds in mice”
    Maickel RP. The Fate and Toxicity of Butyl Nitrites. NIDA Research Monograph. 1988;83:15-27.
    “Skin contact with commercial products containing butyl nitrite can produce a crusty lesion at the site. Repetitive use of the material can lead to a proliferation of these lesions around the nose and lip…Whether inhaled or swallowed, nitrites can produce anoxic states [lack of oxygen]…There is clear evidence that volatile nitrites are used as drugs of abuse…7.9% to 11.1% of high school seniors from 1979 to 1985 reported having tried these drugs…The incidence of deliberate use by homosexual men has been greater…Lowry (1980) conservatively estimated that 250 million recreational doses a year were consumed in the United States.”
    Wood RW. The Acute Toxicity of Nitrite Inhalants. NIDA Research Monograph. 1988;83:28-38.
    “In man, IBN [isobutyl nitrite] could initiate carcinogenesis via the formation of N-nitroso compounds or by a direct reaction with DNA, and HIV could promote KS [Kaposi’s Sarcoma] development, probably via its immunosuppressive action [it is not clear why HIV is brought in here, nor why immunosuppression is required for a cancer, it may be the inability to publish without giving HIV a controlling role in the development of AIDS]
    Mirvish SS, Ramm MD, Babcook DM. Indications from Animal and Chemical Experiments of a Carcinogenic Role for Iso-Butyl Nitrite. NIDA Research Monograph. 1988;83:39-49.
    “The studies presented here [on mice] show that chronic inhalation of AN [amyl nitrites] can lead to a decrease in helper cells, thus alternting the T-cell H/S [Helper=CD4/Suppressor=CD8] ratio, which is the same phenomenon that occurs in AIDS victims. This suggests a link between AN inhalation and cellular immunity depression.”
    Ortiz JS, Rivera VL. Altered T-Cell Helper/Suppressor Ratio in Mice Chronically Exposed to Amyl Nitrite. NIDA Research Monograph. 1988;83:59-73.
    “8 HIV-negative male volunteers gave informed consent to participate in this study…Over 4 days of the second week [after obtaining baseline immunologic data], each volunteer participated in 13 [amyl nitrite and placebo] inhalation sessions…the absolute number of blood lymphocytes decreased significantly following the inhalation protocol, then returned to baseline levels…The results showed that exposure to amyl nitrite can induce changes in immune function even after short exposure to moderate doses.”
    Dax EM et al. Effects of Nitrites on the Immune System of Humans. NIDA Research Monograph. 1988;83:75-80.
    [This paper analyzed 6 studies related to nitrite use and Kaposi’s Sarcoma] [In Study 1, CDC, 1981-82] 84 of the 87 (97%) AIDS cases in the studies reported nitrite inhalant use…60% of KS patients and those with both diseases [KS and PCP] used nitrites more than 384 days compared with 10% of PCP patients…[Study 2, Mount Sinai School of Medicine, 1981-86] A longitudinal study of 42 homosexual men with persistent generalized lymphadenopathy…All 42 participants had used nitrites. The amount of nitrite use was statistically associated with the development of KS…[In Study 3, UCSF, 1983-86] Patients with KS were 2.2 times more likely to report greater than 4 ‘hits’ per night…[this was] the variable most strongly associated with KS…[In Study 4, NCI with 245 men, 1982-]Nitrite inhalant use…was not significantly associated with AIDS, Kaposi’s Sarcoma or Pneumocystis pneumonia [PCP][In Study 5, Multicenter AIDS cohort, 1984-] No association between [reported] nitrite inhalant use and KS was reported. Significant associations for KS were found for decreased hemoglobin level [possibly caused by nitrites], decreased T-helper lymphocyte count [ditto], and increased immunoglobulin A levels…[In Study 6, CDC, including 6,700 men, 1984-]No differences in nitrite use were found between disease groups…Studies begun in 1981 and 192 asked more detailed questions about nitrites than later studies…nitrite inhalant use may be declining since the AIDS epidemic. If so, questions asked in 1985 and 1986 about nitrite use in the previous 6 months or 2 years cannot reflect accurately the amount of nitrite use at earlier times.”
    Haverkos HW. Epidemiologic Studies-Kaposi's Sarcoma Vs. Opportunistic Infections Among Homosexual Men With AIDS. NIDA Research Monograph. 1988;83:96-105.
    “Two other risk factors for the presence of anti-HIV [antibodies in Dutch homosexual men] were the use of cannabis and of nitrite [inhalants]
    van Griensven GJP et al. Risk factors and prevalence of HIV antibodies in homosexual men in The Netherlands. Am J Epidemiol. 1987 Jun;125(6):1048-57.
    http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/125/6/1048.pdf
    “There was a moderate association with nitrite use [in gay men in San Francisco]
    Moss AR et al. Risk factors for AIDS and HIV seropositivity in homosexual men. Am J Epidemiol. 1987 Jun;125(6):1035-47.
    http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/125/6/1035.pdf
    “Multivariate analysis showed that the variable most strongly associated with Kaposi's sarcoma was the use of large quantities of nitrite inhalants...This study suggests that the use of nitrite inhalants may be a cofactor in the development of Kaposi's sarcoma”
    Haverkos HW et al. Disease manifestation among homosexual men with acquired immunodeficiency syndrome: A possible role of nitrites in Kaposi's sarcoma. Sex Transm Dis. 1985;12:203-8.
    “Base on the results of this study and the previously reported toxicity of IBN [isobutyl nitrite], it would appear that pulmonary toxicity and methemoglobin [oxidized form of hemoglobin that cannot reversibly combine with oxygen] formation are the primary effects of subchronic inhalation”
    Lynch DW et al. Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice, I. Systemic Toxicity. J Toxicol Env Health. 1985;15:823-33.
    “The dosages used in this study were chosen based on some preliminary experiments we had conducted to determine the maximal tolerated dose (MTD) of IBN for mice. Those experiments indicated that 300 ppm [the maximum used in this study] was probably close to the MTD...The relevance of these dosages to human usage of these compounds is uncertain because persons who abuse aliphatic nitrites recreationally would have intermittent exposures of variable frequency at very high dosages with chemicals of unknown purity”
    Lewis DM et al. Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice, II. Immunotoxicity studies. J Toxicol Env Health. 1985;15:835-46.
    “For marijuana, the OR [odds ratio of Kaposi's Sarcoma (KS) and/or Opportunistic Infections (OI)] increased from 2.7 to 4.3 with increasing use and for nitrites, the OR increased from 4.0 to 6.3…Of the 50 subjects who used nitrites, 86% also used marijuana. Of the 60 individuals in this study, only 10 [reported that they] never used nitrites (2 with Kaposi's Sarcoma and an Opportunistic Infection and 8 with no symptoms)…Three other drugs were significantly increased among KS/OI patients…These were methyldextro amphetamine, ethyl chloride, and opium.”
    Newell GR et al. Risk factor analysis among men referred for possible acquired immune deficiency syndrome. Prev Med. 1985 Jan;14(1):81-91.
    “A 21-year-old homosexual man presented…complaining of severe headache, nausea, vomiting, chest pain, and shortness of breath. The patient reported that the onset of symptoms had occurred late in the evening prior to admission. He admitted to the ingestion of methaqualone (Quaalude), inhalation of cocaine, and repeated inhalation of 'Hardware' ([brand name for] isobutyl nitrite) every 2-3 minutes for a period of 5-6 hours ending at 11:00 PM the evening before admission. Examination revealed a deeply cyanotic [blue skin due to oxygen deprivation] male in moderate distress…Arterial blood gas samples drawn with the patient breathing room air were extremely dark…Methemoglobin [hemoglobin unable to carry oxygen] was 37% of all hemoglobin [normal values are 1-2%]. The patient was given supplemental oxygen by mask and methylene blue…Approximately 45 minutes later, all symptoms had resolved, and the patient was seen to have normal, pink skin.”
    Guss DA et al. Clinically significant methemoglobinemia from inhalation of isobutyl nitrite. Am J Emerg Med. 1985 Jan;3(1):46-7.
    “Of eight different sex acts, seropositivity correlated only with receptive anal intercourse...and with manual stimulation of the subject's rectum…HTLV-III seropositivity was also associated with frequent nitrite inhalant use during the 12 months before phlebotomy [obtaining a blood sample]…and was inversely correlated with insertive anal intercourse [note that receptive anal intercourse is associated with higher use of nitrite inhalants]
    Goedert JJ et al. Determinants of retrovirus (HTLV-III) antibody and immunodeficiency conditions in homosexual men. Lancet. 1984 Sep 29;2(8405):711-6.
    “Are poppers [nitrite inhalants] immunosuppressive? Hersh et al have demonstrated impaired lymphocyte and monocyte function with doses of nitrites that are not cytotoxic in an in vitro system. They found that these effects were irreversible after 24 hours of continuous exposure...the conversion to nitrosamines could result in increased mutagenic or carcinogenic events”
    Mayer K. Inhalation-induced immunosuppression: sniffing out the volatile nitrite-AIDS connection [editorial]. Pharmacotherapy. 1984 Sep;4(5):235-6.
    “Adverse effects of Nitrites [found in humans or animals, include] ...depression of the central nervous system...convulsions...increased rate and depth of repiration...reduced visual activity...increase in intraocular [within eye] pressure and formation of methemoglobin [which can result in sudden death in humans]...Fatalities have occurred in workers to exposed to strenuous exercise one to two days after cessation of exposure. Loss of vascular tone resulting in pooling of blood has also caused death. The formation of methemoglobin interferes with oxyhemoglobin, causing anoxia. Syncope and death by cardiovascular collapse have occurred...facial dermatitis...local eye irritation...depressed leukocyte function values associated with host defense...The induction of interferon was also inhibited by isobutyl nitrite treatment of fibroblast cell cultures. We showed previously that many chemicals that are carcinogenic can inhibit interferon induction...leukocytes can be permanently damaged by isobutyl nitrite...Many N-nitroso compounds have been shown to be carcinogenic in experimental animals [possibly due to the formation of nitrosamines]...In all, 290 N-nitroso compounds have been tested for carcinogenicity and 252 (87%) have shown such activity...no species is known to be resistant...Organic nitrites which include amyl, butyl, and isobutyl nitrite, can react with amines and amides (amino acids, peptides, proteins and metabolic products) to form N-nitrosamines and N-nitrosamides which are known to be teratogenic [chromosome damaging], mutagenic and carcinogenic”
    Newell GR et al. Toxicity, Immunosuppressive Effects and Carcinogenic Potential of volatile Nitrites: Possible relationship to Kaposi’s Sarcoma. Pharmacotherapy. 1984 Sep;4(5):284-91.
    “Butyl nitrite is predominantly converted to butanol, nitrite, and nitrate in acidic water and to butanol, nitrate, and methemoglobin in whole blood; however, butyl nitrite shows little initial conversion to those products in plasma. Thiol nitrosation of plasma proteins was indirectly demonstrated. Chemical nitrosation of cysteine was deduced spectrophotometrically by the interactions of butyl nitrite with cysteine and 5,5'-dithio(bis)2-nitrobenzoic acid (DTNB). Ames test mutagenicity of n-butyl nitrite was confirmed…The authors join Jorgensen and Lawesson in warning that use of alkyl nitrite may be hazardous”
    Osterloh J, Goldfield D. Butyl nitrite transformation in vitro, chemical nitrosation reactions, and mutagenesis. Journal of Analytical Toxicology. 1984 Jul/Aug;8(4):164.
    “Although a single-infectious-agent hypothesis would seem to explain much of the AIDS epidemic, certain epidemiologic observations remain puzzling. For example, what explains the excess of KS [Kaposi’s Sarcoma] cases among homosexual or bisexual men compared with other AIDS risk groups? Perhaps the route of transmission (sexual vs. nonsexual) of an “AIDS agent” into a susceptible host plays a role in determining clinical outcome. Or perhaps a cofactor present in the homosexual male population, such as repeated exposure to cytomegalovirus or use of inhalant sexual stimulants [e.g. nitrites], predisposes homosexual AIDS patients to develop KS.”
    Jaffe HW, Bregman DJ, Selik RM. Acquired immune deficiency syndrome in the United States: the first 1,000 cases. J Infect Dis. 1983 Aug;148(2):339-45.
    “We speculate that these immunosuppressive effects [measured in cell cultures], combined with the ability of nitrites to convert amines to [carcinogenic] nitrosamines, may be related to the development of opportunistic infections and Kaposi’s sarcoma in homosexuals who use this agent”
    Hersh EM et al. Effect of the Recreational Agent Isobutyl Nitrite on Human Blood Leukocytes and on in Vitro Interferon Production. Cancer Res. 1983 Mar;43(3):1365-71.
    “The carcinogenous potency of N-nitroso compounds [which can be formed within the body from volatile nitrites that are inhaled] is extraordinary. N-nitroso compounds show great organ specificity in their carcinogenic action in animal experiments...volatile nitrites, which are used as inhalants are mutagenic with or without metabolic activation in the Ames test...We therefore find it appropriate to suggest that amyl nitrite may cause Kaposi’s sarcoma in homosexual men”
    Jorgensen KA, Lawesson SO. Amyl Nitrite and Kaposi’s Sarcoma in Homosexual Men. N Engl J Med. 1982 Sep 30;307(14):893-4.
    “Visual observation of stained cell preparations indicated monocyte death [due to exposure to amyl nitrite] occurred more rapidly than lymphocytes. EM revealed broadening of the external foliation of the cell membrane, vesiculation of the outer membrane of the nuclear envelope and a redistribution or loss of microtubule structure in the ectoplasm”
    Marmer DJ et al. In vitro toxicity of Amyl Nitrite [abstract]. Clin Res. 1982;30(5).
    “Amyl nitrite was the only drug that 100% of patients [with Kaposi’s Sarcoma] reported ever having used, although 1 patient reported using it only once in his life…Only amyl nitrite had significantly elevated risk ratios at the [99%] probability level in the time periods 5-9 and > 10 years before disease.”
    Marmor M et al. Risk factors for Kaposi’s Sarcoma in homosexual men. Lancet. 1982 May 15;1:1083-6.
    [we undertook] a survey of male homosexual patients attending [St. Mary's Hospital in London, UK]…250 men were interviewed…215 (86%) had inhaled nitrites within the past five years, a proportion similar to the 86.4% reported for homosexual men attending sexually transmitted disease clinics in New York, San Francisco, and Atlanta”
    McManus TJ et al. Amyl nitrite use by homosexuals. Lancet. 1982 Feb 27;1(8270):503.
    “The [first AIDS] patients are typically young homosexual men, most of whom live in large cities and many of whom use drugs…The leading candidates are the nitrites, which are now commonly inhaled to intensify orgasm. Users of amyl nitrite are more likely than nonusers to have had hundreds of sexual partners and to contract venereal diseases. Preliminary data indicate that this 'liberated' subgroup may be at highest risk for immunosuppression.”
    Durack DT. Opportunistic infections and Kaposi's sarcoma in homosexual men. N Engl J Med. 1981 Dec 10;305(24):1465-7.
    “In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. 2 of the patients died…2 of the 5 reported having frequent homosexual contact with various partners. All five reported using inhalant drugs [probably nitrites], and one reported parenteral [injected] drug abuse.”
    Gottlieb MS et al. Pneumocystis pneumonia - Los Angeles. MMWR. 1981 Jun 5;30(21):250-2.
    “Two cases are reported of Heinz body haemolytic anaemia [breakdown of red blood cells] after the sniffing of amyl nitrite and butyl nitrite for protracted periods. Nitrites are powerful oxidizing agents which are recognized to cause haemoglobin to be oxidized to methaemoglobin”
    Romeril KR, Concannon AJ. Heinz body haemolytic anaemia after sniffing volatile nitrites. Med J Aust. 1981 Mar 21;1:302-3.
    “There is a considerable body of knowledge on the pharmacological and toxicologic effects of amyl nitrite but much less is available on butyl and isobutyl nitrites [which came into use when a prescription requirement for amyl nitrites was introduced]. Considering the fact that these latter compounds have been shown to produce both hypotension [low blood pressure] and methemoglobinemia [conversion of hemoglobin to the inactive form methemoglobin] by the same mechanisms as amyl nitrite, it should be possible to extrapolate the physiological data on amyl nitrite to other members of the same series [including serious cardiac, circulatory and blood abnormalities shortly after use]
    Haley TJ. Review of the Physiological Effects of Amyl, Butyl, and Isobutyl Nitrites. Clinical Toxicology. 1980;16(3):317-39.
    “butyl nitrite inhalation can cause subclinical methemglobinemia [a condition in which the iron in the hemoglobin molecule is unable to carry oxygen effectively] in normal subjects”
    Horne MK et al. Methemoglobinemia from Sniffing Butyl Nitrite. Ann Intern Med. 1979 Sep;91(3):417-8.
    “Amyl nitrite is used widely in the male homosexual population and there are even illegal 'pushers' of this drug. It is used by the passive partner in anal intercourse to relax the anal musculature and thereby facilitate the introduction of the penis.”
    Labataille L. Amyl nitrite employed in homosexual relations. Med Aspects Human Sexuality. 1975;9:122.

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