10th Conference on Retroviruses and Opportunistic Infections

Compiled by Jeff Dearman

Abstract 534

Kaul et al studied the PK of the co-administration of stavudine (d4T XR) with tenofovir disoproxil fumarate (TDF) in 18 seronegative subjects. The subjects were administered scheduled treatment doses of the two medications for 9 days. On day 1, the subjects ate a light meal with a single d4T XR 100mg po dose. The subjects then received TDF 300mg QD po dose with a light meal on days 2 through 8. On the last day of the study (day 9), the subjects ate a light meal with a single dose of both d4T XR 100mg and TDF 300mg. Plasma sampling was drawn over 24 hours on days 1, 8, and 9.

	Cmax (ng/ml)	AUC24 (ng x h/ml)	median Tmax (h)
d4T XR 100mg alone	274 (31)	2,682 (29)	5
d4T XR 100mg + TDF 300mg	275 (26)	2, 765 (28)	4

Geometric mean (CV%)

The authors concluded that dose adjustment was not necessary during the coadministration of TDF and d4T XR.

Abstract 537

Taburet et al performed a prospective, open-label, multicenter study of 53 seropositive male patients receiving a combination of tenofovir (TDF), ritonavir (RTV), or atazanavir (ATV). Only 10 patients finished the PK study. All patients had viral loads of > 10,000 copies/ml and failed antiretroviral treatments with a minimum of 2 PIs and 1 NNRTI. For the first 2 weeks of the study, patients were randomized to receive either 1) unchanged PI and NRTIs or 2) 300 mg QD of ATV, 100 mg QD of RTV, and unchanged NRTIs. All patients then received ATV/RTV, TDF 300 mg QD, and NRTIs for weeks 2-26 of the study. PK parameters measured at week 2 and 6 are listed in the table below.

	ATV				RTV
	Week 2	Week 6 (+ TDF)	Week 6/ Week 2*	P value	Week 2	Week 6 (+ TDF)	Week 6/ Week 2*	P value
Cmax (ng/ml)	4,422	3,190	0.72 [0.50-1.05]	0.06	886	642	0.72 [0.43-1.21]	NS
AUC24 (ng x h/ml)	46,073	34,459	0.75 [0.58-0.97]	0.05	7,011	5,217	0.75 [0.44-1.24]	NS
Tmax (h)	3 (2-5)	5 (1-5)			3 (2-8)	3 (0-5)
Cmin (ng/ml)	636	491	0.77 [0.54-1.10]	NS	43	39	0.91 [0.73-1.13]	NS

*Geometric mean ratio (90% CI)

The authors concluded that TDF may cause decreased levels of both ATV and RTV, however, more study is necessary and the clinical significance is unknown at this time. It is not known whether TDF affects the PK profile of ATV directly or whether RTV plays a role in these PK changes.

Abstract 539

Sankatsing et al studied the potential effects of mycophenolate mofetil [(MMF) trade name CellCept ] in 14 HIV-1 infected male patients. The patients started the following HIV regimen: didanosine 400 mg QD, lamivudine 150 mg BID, abacavir 300 mg BID, indinavir 800 mg BID, ritonavir 100 mg BID, and nevirapine 200 mg BID. Changes in PK parameters of this regimen from the addition of MMF were tested. Intracellular deoxycytidine triphosphate (Dctp), deoxyguanose triphosphate (Dgtp), and triphosphate levels of lamivudine (3TCTP) and abacavir (CBVTP) were also compared in subjects taking MMF. Six subjects were randomized to receive MMF 500mg BID with the antiretroviral regimen above. Plasma sampling was drawn over 12 hours. Plasma AUC₁₂ and clearance did not differ between the 2 groups (MMF or no MMF) for indinavir or abacavir. Patients receiving MMF had significant increases in nevirapine clearance (27%; p = 0.018). All triphosphate levels measured were similar between the 2 groups at all plasma sample times (p > 0.05). The authors concluded that MMF did not affect the PK of IDV, ABC, or triphosphate levels, but did increase NVP clearance of which the clinical significance is unknown.

Abstract 545

Aweeka et al performed a prospective study to evaluate the potential PK effects of ethanol on plasma levels of nelfinavir (NFV) (n = 27) and indinavir (IDV) (n = 8). The subjects were placed into two groups: 1) heavy drinkers (HD) (n = 12) (>70 drinks/month), or 2) light/non-drinkers (LD) (n = 15) (< 30 drinks / month). The HD were tested during acute ethanol use (goal plasma level of 0.10mg/dL) and in the absence of ethanol. LD were used as controls during no ethanol intake to compare to the acute or chronic HD. Plasma AUC_0-τ sampling was drawn over 8h for IDV and 12 h for NFV. Neither the NFV ( n = 15) AUC_0-τ nor the IDV (n = 3) was dependent on drinking group. NFV PK measurements can be found in the table below.

Group	Mean SD of NFV AUC0- ng x h/L)	P value
LD	35,846 19,624
HD acute (HDa)	41,683 12,201	LD:HDa p > 0.05
HD chronic (HDc)	41,912 11,962	LD:HDc & HDa:HDc p > 0.05

The authors concluded that there should be no risk of sub-optimum NFV AUC_0-τ levels caused by ethanol ingestion. The number of subjects receiving IDV was too small to draw any conclusions.

Back to TOP