HIV patients must be exceptionally well briefed by their physicians, and exceptionally alert readers of fine print, to understand that these antiretroviral drugs should not be taken with commonly used, sometimes over-the-counter antihistamines, sleeping pills (sedative hypnotics), or anti-migraine compounds (ergot alkaloids). But that list seems not to be exhaustive, because later (Table 21a) caution is advised when using ritonavir together with antifungals (…conazoles), anti-mycobacterials (clarithromycin, rifabutin, rifampin), hormonal contraceptives, a couple of extra statins beyond those earlier mentioned, anti-convulsants, erectile dysfunction agents, and some miscellaneous substances.
Similarly worrisome details about many other of these drugs confront the reader. It is discomforting that different members of a given group of drugs are likely to have similar “side” effects, in kind if not in intensity, and that the large number of individual names represents only 3 classes of drugs, two of which are present in the standard “combination” “cocktail” treatment. The third class is represented by only two substances, efavirenz (SUSTIVA) and nevirapine (VIRAMUNE). The former has the disadvantage of neuropsychiatric “side” effects and that it produces birth defects in non-human primates. The latter has been the subject of much controversy because of flawed trials in Africa and the death of a pregnant woman in the USA (Celia Farber, “Out of control”, Harper’s, March 2006). The Guidelines describe its “disadvantages” as “Higher incidence of rash than with other NNRTIs, including rare but serious hypersensitivity reactions (Stevens-Johnson Syndrome or toxic epidermal necrolysis); Higher incidence of hepatotoxicity than with other NNRTIs, including serious and even fatal cases of hepatic necrosis; Treatment-naïve, female patients and treatment-naïve patients with high pre-NVP CD4 counts (>250 cells/mm3 females, >400 cells/mm3 males) are at higher risk of symptomatic hepatic events. NVP not recommended in these patients unless benefit clearly outweighs risk.”
One wonders what conceivable benefits could outweigh those risks. The only ones mentioned are “Less fat maldistribution and dyslipidemia than PI-based regimens”.
That equation states that d4T is even more dangerous than ddi, which is just as dangerous as AZT/ZDV. Nevertheless, these apparently more dangerous members of this class are in common use. They feature such additional “side” effects as peripheral neuropathy and pancreatitis (ddI + 3TC); peripheral neuropathy, lipoatrophy, hyperlactatemia and lactic acidosis, reports of progressive ascending motor weakness, potential for hyperlipidemia with stavudine use (d4T + 3TC); higher incidence of mitochondrial toxicity with d4T than with other NRTIs ; bone marrow suppression owing to ZDV (Table 9, p. 63).