Before looking at the studies that support or deny the AIDS-alkyl nitrite hypothesis, I found it helpful to gather some background information about the emergence of AIDS to put the dispute into context. AIDS burst onto the scene in 1981, when clinical investigators became aware that some very rare diseases were occurring in unusually high rates in young homosexual men with no previous health problems. These diseases included Kaposi’s sarcoma (KS) (CDC 1981b; CDC 1982a,e), a rare connective tissue cancer that previously had been seen mainly in older men of Mediterranean or Jewish origin, in Africa among young people and children (American Cancer Society 2006), and in transplant patients receiving immunosuppressive therapy to reduce organ rejection (Gange and Jones 1978; Safai and Good 1981). Opportunistic infections such as Pneumocystis carinii pneumonia (PCP), a rare form of pneumonia, and chronic enlargement of the lymph nodes were also present in many instances (CDC 1981a,b, 1982a; Masur et al. 1981; Gottlieb et al. 1981). With further research, it became clear that that these men had one thing in common: Their immune function was compromised because the cell-mediated aspect of their immune system was impaired by a loss of T-helper cells bearing the CD4 marker on their surface (Gottlieb et al. 1981; Masur et al. 1981; Siegal et al. 1981; Ammann et al. 1983a).
Such rare diseases in young men with no history of illness or immunosuppressive therapy had never been seen before in the history of medicine. Thus began the long and frustrating search for a cause. Not surprisingly, in the early stages of this research, scientists came to the rational conclusion that, because initially only homosexual men displayed this unique set of symptoms, some aspect of the gay lifestyle might be playing a role in the development of this disease (Goedert et al. 1982; Sonnabend et al. 1983; Mavligit et al. 1984). Many young men with AIDS symptoms also reported using poppers, a popular recreational inhalant among homosexuals at the time. As one of several behavioral aspects unique to the homosexual lifestyle, poppers were investigated during these early stages as a possible link to the syndrome. It was an interesting hypothesis, but one that would be ruled out relatively quickly. The first cracks in the hypothesis occurred when clinicians began to see the syndrome in populations outside of the homosexual community. Hemophiliacs and other recipients of blood products, injection drug users, female sexual partners of bisexual males, and infants born to females with the syndrome or a past history of injection drug use—all of these cases pointed to a new hypothesis that the disease was caused by a blood borne agent, such as a virus (CDC 1982b,c,d,e, Masur et al. 1982; 1983a; Ammann et al. 1983b; Davis et al. 1983; Elliot et al. 1983; Harris et al. 1983; Poon et al. 1983; Rubinstein et al. 1983).
Despite these findings, scientists continued to pursue the AIDS-alkyl nitrite hypothesis by completing a series of large and well-designed research studies that investigated the link. Although it may seem counterintuitive, it is simply good science to investigate a hypothesis until it is either repeatedly shown to be false or continues to stand up under continued scientific scrutiny. In this case, the hypothesis failed to stand up to the scrutiny of several studies. The results of the largest of these studies, referred to as the MACS (Multicenter AIDS Cohort Study) Project, were published in the prestigious New England Journal of Medicine in 1987 (Polk et al. 1987). This study investigated 1835 HIV positive homosexual men, 59 of which developed AIDS in the course of the 15-month study. One of many aspects studied in this long-term investigation was the possible role of alkyl nitrites in both AIDS and KS; no link was found (Polk et al. 1987; Voeller 1990). Another large-scale study by the New York Blood Center supported these findings (Stevens et al. 1986), as did other smaller studies (Vandenbroucke 1989; Schechter et al. 1993). The Schechter study was particularly definitive. In this study, 715 homosexual men were studied for nearly nine years. Of the 365 HIV-positive men, 136 subsequently developed AIDS. No cases of AIDS occurred in the HIV-negative men, even though they reported considerable use of alkyl nitrite inhalants (Schechter et al. 1993).
In my mind, these studies cleanly sever any possible link between AIDS and inhalation of alkyl nitrites. Science has confirmed what my mind had already surmised: a compound used for over 150 years by countless people to treat angina and cyanide poisoning could not be a casual factor in a disease that first appeared 25 years ago. It simply doesn’t make sense. It seems that many proponents of the alkyl nitrite-AIDS connection also saw the light. Leaving this initial hypothesis behind, researchers soon began to entertain new questions: Could alkyl nitrites accelerate the progression of AIDS by further compromising the immune system? Could they play a role in the development in KS, a disease seen mainly in the homosexual AIDS population? Here are two more interesting questions in the quest for definitive answers. How would the research findings deal with these new questions? Would well-designed studies support or refute these hypotheses?
