HAART regimens

Makela and colleagues described the occurrence of a probable recurrent GBS six weeks after initiation of HAART and after a striking increase in CD4 cell count in an HfV-infected individual (Makela et al. 2002). Piliero and colleagues described an HIV-infected patient with AIDS who developed GBS, 26 days after initiation of a 6-drug HAART regimen, which had led to an impressive immune reconstitution (a rise in CD4 cell count from 31 to 602 cells/pL) (Piliero et al. 2003). Puthanakit and colleagues identified a child who developed GBS, 3 weeks after initiation of efavirenz-based HAART in a cohort of HIV-infected Thai children (Puthanakit et al. 2006). 

For ATN, it is reasonable to decrease the dose or discontinue the offending NRTl and change the HAART regimen if available. Failing this, the patient may need to continue the regimen with the addition of pain-modifying drugs. After discontinuation of a toxic NRTl, symptomatic improvement can be expected in most individuals within several months (Blum et al. 1996). 

Like lamivudine, the M184V/I mutation is most frequently associated with emtricitabine use and may emerge rapidly in patients receiving HAART regimens that are not fully suppressive. Because of their similar mechanisms of action and resistance profiles, the combination of lamivudine and emtricitabine is not recommended. 

Support for the hypothesis of a casual relation between stavudine and lipodystrophy comes from another randomized study in which stavudine-containing HAART regimens were switched to a combination of zidovudine, lamivudine, and abacavir (157). Eight patients were randomized to continue stavudine and 14 patients switched to the triple combination. Imbalance in the treatment arms resulted from exclusion of patients who maintained treatment for a minimum of 6 months of follow up. Over 48 weeks after randomization, the average leg and arm fat mass fell in the continuation arm but increased in the switch arm. One patient in the switch arm, who had previously taken zidovudine and lamivudine, had a therapeutic failure. 

Eyer-Silva WA, Neves-Motta R, Pinto JF, Morais-De-Sa CA. Inflammatory oedema associated with lopinavir-including HAART regimens in advanced HFV-l infection report of 3 cases. AIDS 2002 16(4) 673-4. 

Significant hepatic deterioration, consistent with cholestasis, occurred 5 months into a HAART regimen including nevirapine (12). 

In those who are opioid-dependent, methadone can facilitate adherence to HAART regimens. The pharmacokinetics of the tablet formulations of didanosine and stavudine have been studied in 17 individuals taking stable methadone therapy in comparison with 10 untreated controls (33). Methadone reduced the AUCo 6 by 63% for didanosine and by 25% for stavudine and the C ax by 66% and 44% respectively. These effects appeared to result primarily from reduced systemic availability. Trough concentrations of methadone were comparable to those seen in historical controls, suggesting that the nucleoside analogues did not affect methadone disposition. The authors concluded that larger doses of the tablet formulation (or another type of formulation) may be necessary to provide HAART in subjects taking methadone. 

Pharmacokinetics and clinical uses Lamivudine is used orally in HAART regimens for HIV and adjunctively with interferon alpha in HBV infection. Dosage adjustment is needed in patients with renal insufficiency. 

Pharmacokinetics and clinical uses Stavudine is used in HAART regimens. The drug has good oral bioavailability and penetrates most tissues, including the CNS. Dosage adjustment is needed in renal insufficiency. 

D. Effects on Carbohydrate and Lipid Metaboiism The use of protease inhibitors in HAART drug combinations has led to the development of disorders in carbohydrate and lipid metabolism. It has been suggested that this is due to the inhibition of lipid-regulating proteins which have active sites with structural homology to that of HIV protease. The syndrome includes hyperglycemia and insulin resistance or hyperlipidemia, with altered body fat distribution. Buffalo hump, gynecomastia, and truncal obesity may occur with facial and peripheral lipodystrophy. The syndrome has been observed with protease inhibitors used in HAART regimens, with an incidence of 30-50% and a median onset time of approximately 1 year s duration of treatment. 

Items 92-93. A 30-year-old hospitalized AIDS patient has a CD4 cell count of 50/ tL. He is being treated with a highly active antiretroviral therapy (HAART) regimen consisting of zidovudine (ZDV), lamivudine (3TC), and indinavir. Other drugs being administered to this patient include acyclovir, clarithromycin, foscamet, rifabutin, and trimethoprim-sulfamethoxazole. 

The concurrent use of fluconazole and nevirapine doubled the exposure to nevirapine compared with historical control data, although nevirapine did not have any clinically relevant effect on fluconazole pharmacokinetics. The manufacturer suggests that patients should be closely monitored for nevirapine-associated adverse effects if fluconazole and nevirapine are used concurrently. However, in a retrospective study of patients who had received a nevirapine-based HAART regimen, there was no increase in the incidence of clinical hepatitis, elevated aminotransferases or skin rashes, when the outcomes of225 patients not receiving fluconazole, 392 patients treated with fluconazole 400 mg weekly, and 69 patients receiving fluconazole 200 mg daily with nevirapine were compared. ... 

Calcium supplements had no effect on plasma levels of nelfinavir or its M8 metabolite in 15 patients receiving nelfinavir 1.25 g twice daily as part of a HAART regimen. Calcium was given as calcium carbonate 1350 mg twice daily to 9 patients, and calcium gluconate/calcium carbonate 2950/300 mg twice daily to 6 patients, both for 14 days. Plasma levels of nelfinavir were measured before a dose and 3 hours after a dose. Similar results were reported in another study. No nelfinavir dosage adjustments appear necessary if calcium supplements are given. 

A LUV-positive patient taking ciclosporin 250 to 350 mg twice daily (to maintain a therapeutic ciclosporin trough level of 300 to 400 nanograms/mL) was restarted on his usual HAART regimen of teno-fovir, lamivudine and fosamprenavir 1.4 g twice daily on day 12 post-liver transplantation. Within 2 days, the ciclosporin level had increased to 600 nanograms/mL, requiring a ciclosporin dose reduction to 100 mg twice daily. ... 

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