At the beginning of the 1990s, therapy for HIV usually consisted of one anti-HIV drug taken several times a day. This drug was one of several nukes — generally AZT, ddI or ddC. (The latter drug is hardly ever used in North America in 2002.) In the early to mid-1990s, as more nukes became available, doctors increasingly began to prescribe combinations of these drugs. Not considered potent today, combinations of two nukes were, for a time, able to increase or maintain CD4+ cell counts in some people with HIV/AIDS (PHAs). Up to the mid-1990s, the side effects generally associated with nukes included the following:
By 1996, a new class of drugs called protease inhibitors (PIs) became available in high-income countries. When used in combination with nukes or non-nukes, PI-based therapy has powerful anti-HIV effects and raised CD4+ cell counts to very high levels in people with AIDS. A benefit of PI-based therapy was that many PHAs began to recover from previously hard-to-treat complications of AIDS. As a result, fewer PHAs were dying. As more and more PHAs heard about or experienced the dramatic results of PIs, a new optimism emerged. Complaints about PI-based regimens at that time were generally limited to nausea and diarrhea with the odd report of kidney stones in indinavir (Crixivan) users.
In 1997 a number of reports appeared about unusual side effects in PHAs using combination therapy. First, there was a report of higher-than-normal levels of blood sugar that developed in people who did not have diabetes. More troubling was a report from Atlanta about strange changes in body shape. The report involved a man who had developed pads of fat on and around his shoulders — a feature commonly called a "buffalo hump." He had been using AZT for three years, 3TC for eight months and the PI indinavir for six months when the buffalo hump developed. The doctors were puzzled — buffalo hump was not commonly reported to occur in HIV/AIDS. It has been known to happen in "male alcoholics" and in others with a hormonal disorder called Cushing's syndrome. However, tests revealed no obvious hormonal disorders and the man did not drink alcohol. The doctors suspected that his problem was caused by the use of indinavir.
The published report of the buffalo hump was followed by similar reports on the Internet written by PHAs on an e-mail list called "Crix list." Because buffalo humps had not been previously associated with HIV or therapy for HIV and because PIs were relatively new on the scene, people assumed that PIs were the cause of the "new" problem. But, in 1998, doctors in San Francisco published a report on eight PHAs (all male) who developed buffalo humps while on anti-HIV therapy. What was interesting about this report is that four of the subjects were taking only one or two nukes and no PIs. The treatments used by the eight PHAs were as follows:
Below are some key points about these eight PHAs:
The researchers were stumped as to why the buffalo humps developed. What is clear from this study is that buffalo humps (fat deposits) can occur in PHAs who are taking nukes without PIs. Into the late 1990s, other aspects of body shape changes appeared, which are detailed in our next report.
REFERENCES
1. Lo JC, Mulligan K, Tai VW, et al. "Buffalo hump" in men with HIV-1 infection. Lancet 1998;Mar 21;351(9106):867-70.
2. Hengel RL, Watts NB and Lennox JL. Benign symmetric lipomatosis associated with preotease inhibitors. Lancet 1997 Nov 29;350(9091):1596.
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