Virological failure

Data were pooled from the TORO-1 and -2 studies for 48 week efficacy analyses (Nelson et al. 2005). These generally confirmed the 24 week findings and also demonstrated the durability of virological response - in both the enfuvirtide -h OB and OB only groups only about 7% of patients met virological failure criteria between 24 and 48 weeks. 

Lalezari JP, Bellos NC, Sathasivam K, Richmond GJ, Cohen CJ, Myers RA Jr, Henry DH, Rask-ino C, Melby T, Murchison H, Zhang Y, Spence R, Greenberg ML, Demasi RA, Miralles GD (2005b) T-1249 retains potent antiretroviral activity in patients who had experienced virological failure while on an enfuvirtide-containing treatment regimen. J Infect Dis 191 1155-1163... 

Melby T, DeMasi R, MiraUes G, HeUek-Snyder G, Greenberg M (2005) Evolution of enfuvirtide resistance in longitudinal samples obtained after continued enfuvirtide dosing post-virological failure. In 14th international drug resistance workshop, QC, Canada. Antiviral therapy, Suppl 1... 

Landman R, Descamps D, Peytavin G, Trylesinski A, Katlama C, Girard PM, Bonnet B, Yeni P, Bentata M, Michelet C, Benalycherif A, Brun VF, Miller MD, Flandre P (2005) Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HlV-1 infection TONUS study, HIV Clin Trials 6 291-301... 

Podzamczer D, Ferrer E, GateU JM, Niubo J, Dalmau D, Leon A, Knobel H, Polo C, Iniguez D, Ruiz I (2005) Early virological failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10 171-177... 

Two classes of entry inhibitors have been developed. The first entry inhibitor approved as HIV therapy was enfuvirtide, a fusion inhibitor. In contrast with aU other antiretrovirals, this drug must be administered subcutaneously and twice a day, which represent important disadvantages to the patient. It is very potent and generally reserved for heavily antiretroviral-experienced patients with virologic failure. Unfortunately enfuvirtide shows a low genetic barrier for resistance (Fig. 2) and should be administered in combination with at least one other active drug. 

Clinical event Assess need for ART Assess need for Ol chemoprophylaxis Start therapy in appropriate patients Start therapy when less than 200 cells/mm3 Clinical event or decrease in CD4+ T-cell count Receiving ART assess if event is due to virologic failure Not receiving ART assess need to begin therapy Change regimen if needed (drugs or doses) Start therapy in appropriate patients... 

TABLE 84-4. Treatment Options Following Virologic Failure with the Initial Regimen... 

Proportion of subjects responding (i.e., not demonstrating virologic failure) based on the FDA Time to Loss of Virologic Response Algorithm (time frame 48 weeks)... 

Atazanavir without ritonavir is not recommended for treatment-experienced patients with prior virologic failure. 

Hepatic function impairment Give with caution in patients with mild to moderate hepatic insufficiency. Consider a dosage reduction to 300 mg once daily for patients with moderate hepatic insufficiency (Child-Pugh class B) who have not experienced virologic failure. Do not use atazanavir in patients with severe hepatic insufficiency (Child-Pugh class C). 

Resistance to maraviroc is associated with one or more mutations in the V3 loop of gpl20. There appears to be no cross-resistance with drugs from any other class, including the fusion inhibitor enfuvirtide. However, virologic failure of regimens containing maraviroc may potentially be caused not only by resistance but also by emergence... 

Although virologic failures have been uncommon in clinical trials of raltegravir to date, in vitro resistance requires only a single point mutation (eg, at codons 148 or 155). The low genetic barrier to resistance emphasizes the importance of combination therapies and of adherence. Integrase mutations are not expected to affect sensitivity to other classes of antiretroviral agents. 

Lucas GM, Chaisson RE, Moore RD (1999) Highly acdve andretroviral therapy in a large urban clinic Risk factors for virologic failure and adverse drug reacdons. Arm hr tern Med 131 81-87. 

Price RW, Paxinos EE, Grant RM, Drews B, Nilsson A, Hoh R, Hell-mami NS, Pedopoulos CJ, Deeks SG (2001) Cerebrospinal fluid response to sductured deatment interrupdon after virological failure. AIDS 15 1251-1259. 

Rodriguez-Rosado R, Jimenez-Nacher I, Soriano V, Anton P, Gonzalez-Lahoz J (1998) Virological failure and adherence to andredovi-ral therapy in HIV-infected padents [letter]. AIDS 12 1112—1113. 

Ginkgo biloba Virological failure in a 47-year-old HIV-infected patient who had taken antiretroviral drug therapy for 10 years was associated with falling efavirenz plasma concentrations after he started to take Ginkgo biloba [156" ]. 

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