Antiretroviral drugs adverse effects

The development of antiretroviral therapy has been a major challenge since the discovery of the human inununodeficiency virus (HIV). Early successes with nucleoside and non-nucleoside reverse transcriptase (RT) inhibitors, as well as the development of protease inhibitors have facilitated, in recent years, a highly active antiretroviral therapy (HAART), where a combination of drugs is simultaneously administered. In spite of significant improvements in the morbidity and mortality of HIV-infected patients, the rapid appearance of resistant HIV-variants, as well as adverse effects and high cost of contemporary drugs necessitate the continuous development of independent classes of anti-HIV agents. ... 

The most common adverse effects associated with enfuvirtide therapy are local injection site reactions. Hypersensitivity reactions may rarely occur, are of varying severity, and may recur on rechallenge. Eosinophilia has also been noted. In one prospective clinical trial, an increased rate of bacterial pneumonia was noted in patients receiving enfuvirtide. No interactions have been identified that would require the alteration of the dosage of other antiretroviral drugs. 

Lipodystrophy is a common adverse effect of antiretroviral drugs, particularly the NRTIs and has been reported with zidovudine (1209). 

Nolan D, Reiss P, Mallal S. Adverse effects of antiretroviral therapy for HIV infection a review of selected topics. Expert Opin Drug Saf. 2005 4 201-218. 

The most frequent adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea can be dose-limiting but often responds to antidiarrheal medications. Like the other protease inhibitors, nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur as described above. Interactions with antiretroviral agents are summarized in Table 49-4 others may be found in Table 4-2. 

However, gynecomastia has also been reported in 15 patients taking a variety of antiretroviral drugs (18). The authors suggested that it was due to increased cytokine concentrations following immune restoration and this adverse effect may therefore not be unique to efavirenz among drugs used to treat HIV infection. 

The adverse effects of erythropoietin in neonates are minimal compared with adults. There were no hypertensive effects reported and no effect on development and growth measured at 18-22 months (111). In a multicenter, randomized, double-blind trial in 21 anemic HIV-infected children, who were concomitantly treated with antiretroviral drugs, epoetin was effective and safe (112). 

A variable-dose plasma concentration-controlled approach to combination antiretroviral therapy (zidovudine, lamivudine, and indinavir) has been compared with conventional fixed-dose therapy in 40 patients in a randomized, 52-week, open trial (8). Significantly more concentration-controlled recipients achieved the desired concentrations for all three drugs there was a good response in 15 of 16 concentration-controlled recipients compared with nine of 17 conventional regimen recipients. However, there was no difference in the occurrence of drug-related clinical events or laboratory abnormalities between the two regimens. Three patients withdrew because of gastrointestinal adverse effects, one because... 

As mentioned previously, some infectious diseases pharmacists have established effective clinical practices in the outpatient setting. The most common example of this is the presence of a pharmacist in an HIV clinic. The myriad of antimicrobial drug interactions and adverse effects associated with antiretroviral therapy, the need to periodically assess antiretroviral efficacy, and the considerable potential for noncompliance literally necessitate the need for a pharmacist in any established HIV clinic. Infectious diseases pharmacists work with infectious diseases and/or immunology physicians. Pharmacists conduct medication histories and answer drug information questions. In some settings, they may act under protocol to assess patient response to antiretroviral therapy based on virologic and immunologic measures, and to make appropriate modifications in therapy. 

The use of any drug, even as a prophylactic measure, may be associated with adverse effects. Adverse effects of antiretroviral medications are well-described in the HIV population however, there is sparse data about adverse effects in the non-HIV-infected individuals. Between October of 1996 and December of 1998, an HIV post-exposure prophylaxis registry prospectively followed... 

South African patients, of whom 141 were coinfected with HTV, 23 taking antiretroviral drugs [32 . Details of serious adverse events were ascertainable in 331 patients and occurred in 27% of HIV-infected and 13% of HIV-uninfected individuals. The excess was attributable to increase incidences of peripheral neuropathy (8.3% versus 1.9%) and persistent vomiting (13% and 3.3%). The occurrence of serious adverse events was not related to antiretroviral drug use, although median CD4 cell counts were lower in those with adverse effects (130 versus 259 X 10 /1). 

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