A problem with Wilson’s references that lessens credibility is that many of the articles are not published in peer review journals. It is much easier to publish scientific articles in these types of journals, because the data and conclusions are not reviewed by experts in that particular field. In addition, some of the journals referred to are somewhat obscure and not found in medical school libraries, which carry a large number of the best and most used medical journals. An additional infirmity of the references listed by Wilson is that some of them are data presented at meetings as posters or informal talks. These types of presentations are usually not referenced in scientific publications because they are not peer reviewed and nearly always are preliminary data that has not been confirmed or published. It is difficult to critique these references because they are not published or found in easily obtainable publications. Finally, one of the references was submitted, but not accepted for publication. Articles that were rejected for publication are never cited in credible reference lists.
Woody, et al (1999) Non-injection substance use correlates with risky sex among men having sex with men: data from HIVNET. Drug and Alcohol Dependence 53:197.
Associations between substance use and sexual behavior were examined among 3220 seronegative men. The odds ratio (OR) was low for nitrite inhalants (some use-OR= 1.6, heavy use-OR= 2.18). This is in dramatic contrast to other studies, some of which give OR’s as high as 33. The large range of OR’s indicates a lack of consistency between results.
Although there appears to be a relationship between alcohol or drug use and an increased sexual risk among MSM, it is clear that these relationships are complex and difficult to evaluate. Disparate findings can be explained in many ways including inability to evaluate substance use patterns in the context of the sexual encounter, comparing populations with different ages or cultural features, and limitations in power resulting form small sample sizes which make it impossible to evaluate possible confounds such as demographic contributions of different substances of levels of use. Here the respondents state nitrate use is 29%, compared to marijuana use 49% and alcohol use 89%, nitrite use is the lowest percentage, suggesting that it is less related to risky sex than other substances.
Ekstrand, et al. (1999) Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status AIDS, 13:1525.
This paper examined patterns and factors that correlate with unprotected anal intercourse (UAI) practices among 510 San Francisco gay men. They reported that 52% of high transmission risk men (those who reported having sex with a partner of unknown or discordant HIV antibody status) used nitrate inhalants in the previous 12 months, compare to 20 and 25% of no and low transmission groups and 14% (compare to 4% of low and no transmission groups) using at least once-a-month. All groups reported two-three drugs used and alcohol use again which precludes accurate interpretation.
Strathdee, et al (1998) Determinants of sexual risk-taking among young HIV negative gay and bisexual men. J of Acquired Immune Deficiency Syndrome and Human Retrevirology,19:61, 1998.
Independent predictors of sexual risk-taking were low education, nitrite use, low social support, nonconsensual sex. This study reported an OR of 1.6 for nitrite use, which is not very high.
The relationship between sexual risk and inhalant use may represent a decision that is made about how a sexual relationship will be carried out rather than a pharmacological effect of the inhalant.
Stall, et al. (1986) Alcohol and drug use during sexual activity and compliance with safe sex guidelines for AIDS: The AIDS behavioral research project.
This study stated that men who increased their risky sexual behavior also increased their alcohol and drug use and those who decreased their risky behavior also decreased their .alcohol and drug use. Again, nitrite use was not isolated from other drugs. Furthermore, a change in correlative behaviors may simply reflect an overall lifestyle change in a direction that may or may not promote health.
Kalichman (1997) Continued high-risk sex among HIV seropositive gay and bisexual men seeking HIV prevention services. Health Psychology, 16(4):369.
In this article, only 19% of the HIV-positive men surveyed used nitrite inhalants, with the average frequency of use over a three month period being 1.9 times. Furthermore, of the men who engaged in unprotected anal sex, the average frequency of nitrite use over a three month period was only 3.3 times, compared to a mean frequency of use of 0.6 times for those who did not have unsafe sex. Although the author used statistics to show a significant difference between those who did and did not have unprotected anal sex, the raw data indicates an extremely low use of nitrites among any of the men. It is highly unlikely that using a drug 3.3 times over a three month period can cause unsafe sex. This is a good example of how statistics can be used to mislead the reader.
As a final note, the nationwide prohibition on sales of volatile nitrites in the United States in 1991 has not had an appreciable effect on either the use of inhalant nitrites by men in the Chicago MACS/C. Since nitrites are readily available by mail order and in pornographic bookstores and movie theaters, it appears that legal prohibition does not change abuse behaviors. In fact, use of these "street drugs" could be more dangerous because they may have harmful impurities.
This drug is probably one of the safer drugs of abuse that are available, particularly because the effects are transient. In addition, this drug is inexpensive compared to other drugs of abuse, and use of nitrites rather than the more expensive drugs may actually decrease crime and prostitution, which are commonly used by drug abusers to obtain drugs. A lower incidence of prostitution may lead to lower levels of unsafe sex in these groups, which may be a better preventative of HIV infection than other intervention methods.
An Epidemiologic Survey of HIV Risk Behaviors Among MSM ins a Resort Area: the South Beach Health Survey, Miami, Florida oral report presented at the Northwest Regional Workshop on HIV Preventions Approaches for Alcohol and Drug Use Among Men Who Have Sex With Men Webster. Popper use during sex was the only drug significantly related to unprotected anal intercourse in this sample of MSM p=.0495
A potential mechanism is that both substance use and sexual behavior may occur within the context of long-standing social networks. Correlational data do not prove causality.
Ostrow, et al. (1995) A case-control study of human immunodeficiency virus type I seroconversion and risk-related behaviors in the Chicago MACS/COS cohort. American Journal of Epidemiology, 142(8):875.
This study found that seroconversion correlated with marijuana, cocaine, and nitrite, but not alcohol use. This contradicts other studies finding that a relationship of alcohol use with HIV infection. Furthermore, it was not reported if subjects used other drugs in conjunction with nitrates.
Ostrow, et al. (1994) Recreational drugs and sexual behavior in the Chicago MAC/CCS cohort of homosexually active men. Journal of Substance Abuse, 5(4):311.
This study stated that stopping nitrite use was unrelated to improvement in safer sexual behavior, which again refutes Wilson's claim. In addition, they reported that nitrite use was associated with failure to use condoms during receptive anal sex among non-monogamous men only. If inhalation of nitrites was truly a causative factor in unsafe sex, it would prevail in monogamous as well as non-monogamous relationships. More importantly, a cessation of drug use would lead to safer sex.
Ostrow, et al. (1990) Recreational drug use and sexual behavior change in a cohort of homosexual men. AIDS, 4:759.
This article reported that homosexual men who use nitrites are in a higher risk category for sexual behavior. They stated that 80.6% of the highest risk group was nitrite users. However, 72.5% of the same risk group did not use drugs. These percentages are not very different, particularly when one takes into account experimental variability.
deWit, et al. (1994) Time from safer to unsafe sexual behavior among homosexual men. AIDS, 8{1):123.
In this short communication (a type of article that presents preliminary data), the authors state that both a younger age and nitrite use were predictors of a shorter time to unsafe sexual behavior. No other drugs were studied. Perhaps younger men tend to have more unsafe sex and this group also uses drugs more frequently, which is not necessarily correlative with the incidence of unsafe sex.
Letup, et al. (1994) Seroprevalence of HIV and risk behaviors among young homosexuals and bisexual men. Journal of the American Medical Association, 272(6):449.
Homosexual and bisexual men recruited for this study were located in public places in San Francisco and Berkely, including street corners, dance clubs, bars, parks, and other public venues frequented by homosexuals, which is not a random sampling of homosexual and bisexual men. Of the respondents who did not use nitrites during (n=371), 30% had unprotected anal sex, whereas of the 35 men who claimed to use nitrites during sex, 60% engage in unsafe sex. They claimed that nitrite use is a predictor of unsafe anal sex. From this bit of data, one cannot make such a claim.
Finally, the author gives the disclaimer that is predominant in the studies presented by Wilson: "However, our data cannot distinguish whether this represents a causal association, with abuse leading to impaired judgment or disinhibition, or a marker of lifestyle among persons at high risk."
Hogg, et al. (1993) Sociodemographic correlates for risk-taking behaviors among HIV seronegative homosexual men. Canadian Journal of Public Health. 84:423.
In this paper, the majority of the men in this study were white and part of a large urban gay community, which is a homogenous population of homosexual and bisexual men. The investigators found that 55% of risk takers (n=31) used nitrite inhalants compared with 30% of the control group (n=108). It is interesting that only about half of the risk-takers use nitrites. Of the non-risk-takers, a relatively large percentage used nitrites (30%), from which one could imply that the use of this drug is also associated with safe sex. In addition, they found no differences between risk and non-risk takers for cocaine, marijuana, or other drugs, which contrasts from other studies. Finally, the author states that this type of behavior should not be taken to identify all people who take risks.
Paul, et al. (1994) Correlates of sexual risk-taking among gay male substance abusers. Addiction, 89:971.
This paper reported that of the men in this study who have unprotected anal sex, 19.9% used nitrites in the past 90 days. One cannot establish a role for nitrites in unsafe sex. using this data. If nitrite inhalation caused unsafe sex, this percentage would be much higher. At meeting of the Center for Disease Control on the connection between KS and poppers, this investigator discussed the complexities of classifying events as "risky" or "safe". There are many confounding effects among sexual behavior, drug use, and other likely health risks. He emphasized that one could never conduct a controlled study (survey) to answer the question of causality.
Robins, et al. (1997) Do homosexual and bisexual men who place others at potential risk for HIV have unique psychosocial profiles? AIDS Education and Prevention 9(3):239.
This article has very little data (two tables). Although they claim that HIV-positive (n=369) homosexual and bisexual men exhibit more frequent nitrite use than HIV-negative (n=156) men, there is not a significant difference between the two groups.
Men engaging in risky sexual practices reported more popper use than men practicing safer sex, although his effect was not significant. They also tended to use more alcohol than the safer sex group. This study reported that for the variables they studied (demographics, social support, psychological status, coping, substance use) the correlates of risky behaviors were the same in HIV positive and negative men. The study's cross-sectional design does not allow one to draw causal inferences and this article does not support Wilson's hypothesis.
Tabet, et al. (1998) Incidence of HIV and sexually transmitted diseases (STD) in a cohort of HIV-negative men who have sex with men (MSM). AIDS,12:2041.
This provides no useful information. It was performed with 578 HIV negative men in Seattle. The authors compared risk factors for STD with nitrite use (OR =2.3) and STD with UAI (OR =2.6). Tabet found urethritis the most common STD did not compare nitrite use with AIDS.
Barett, et al. (1998) Redefining gay male anal intercourse behaviors: implications for HIV prevention and research. The J of Sex Research 35:381.
Data comes from a multivariate analysis study of HIV risk behaviors in 1001 males who self-identified as homosexual or reported unprotected oral or anal sex with another man in the previous five years. This another example of non-related research.
Myers, et al (1996) Sexual risk and HIV-testing behaviour by gay and bisexual men in Canada. AIDS CARE, 8:297.
This article is irrelevant to the subject. Only the abstract was available and no mention of nitrite use was made. Self reports of 4803 men identified from gay venues focused on unprotected sex and test taking.
Seigel, et al. (1989) Factors distinguishing homosexual males practicing risky and safer sex. Social Science Medicine, 28:561.
Again, the author does not distinguish what type of drug use is associated with risky behavior, which invalidates any assumption that nitrites are involved. In addition, they survey men from street corners, dance clubs, bars, parks, and other public venues frequented by homosexuals, which is not a random sampling of homosexual and bisexual men. Of the respondents who did not use nitrites during (n=371), 30% had unprotected anal sex, whereas of the 35 men who claimed to use nitrites during sex, 60% engage in unsafe sex. They claimed that nitrite use is a predictor of unsafe anal sex. From this bit of data, one cannot make such a claim.
Finally, the author gives the disclaimer that is predominant in the studies presented by Wilson: "However, our data cannot distinguish whether this represents a causal association, with abuse leading to impaired judgment or disinhibition, or a marker of lifestyle among persons at high risk."
Martin, (1990) Drug use and unprotected anal intercourse among gay men. Health Psychology, 9(4):450.
Results are reported from a longitudinal study of 604 NYC gay men spanning four 12-month periods from 1980 to 1987 indicating that as the acquired AIDS epidemic progressed, the link between drug use and high risk-sex diminished. Furthermore, initiation of drug use with sex is not associated with subsequent increases in lower rates of unprotected anal intercourse.
In this report, participants were asked how many times they used drugs in conjunction with unsafe sex over the past year. This type of question is obviously subject to recall bias. Another problem with this study is that respondents who used one type of drug were likely to use other drugs as well, which confounds the issue of nitrite use being directly related to unsafe sex.
The author found that there was a correlation between men using drugs (including nitrites) with unsafe sex and that both behaviors decline over a seven year period. These behaviors declined to the point that none of the associations between any specific drug use and unprotected receptive anal intercourse were statistically significant, which Wilson failed to mention.
Interestingly, within this article, the author reported contradictory results. They found that there is no consistent pattern associating initiation of drug use with sex and high-risk intercourse, either receptive or insertive. This type of data further refutes the hypothesis that nitrite use influences risky behavior.
Finally, the authors stated that "We have evidence that favors (but that no means confirms) a causal interpretation of the link between drug use and high-risk sex among gay men.
On the other hand,...noncausal interpretations of the link between drug use and risk taking may be more parsimonious." In the discussion section of the paper, they say that "conclusions based on an epidemiologic field study of the kind we have conducted are subject to threats to validity, particularly to drawing causal inferences." These kinds of statements do not support Wilson's hypothesis.
