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Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.

Ouattara E, Danel C, Moh R, Gabillard D, Peytavin G, Konan R, Carrou JL, Bohoussou F, Eholie SP, Anglaret X - J Int AIDS Soc (2013)

Bottom Line: Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal.We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire.NCT00495651.

View Article: PubMed Central - PubMed

Affiliation: Programme PACCI, Abidjan, Côte d'Ivoire; Univ. Bordeaux, ISPED, F-33000 Bordeaux, France.

ABSTRACT

Introduction: Tenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.

Methods: Participants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3-4 AEs or persistent grade 1-2 AEs leading to drug discontinuation.

Results: A total of 197 patients (76% women, median CD4 count 395/mm(3)) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In-patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1-4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.

Conclusions: We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub-Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in-patients taking other drug regimens.

Clinical trial number: NCT00495651.

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Early drug discontinuation and viral load suppression at six months in patients who started ART with TDF-FTC-EFV or TDF-FTC-ZDV. LTFU: lost-to-follow-up; M6: Month-6.
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Figure 0001: Early drug discontinuation and viral load suppression at six months in patients who started ART with TDF-FTC-EFV or TDF-FTC-ZDV. LTFU: lost-to-follow-up; M6: Month-6.

Mentions: At the Month-1 visit, a higher percentage of patients on ZDV reported having interrupted their treatment for more than seven days and/or having missed at least one pill during the past four days (Table 2). At the Month-6 visit, there was a trend towards a lower gain in CD4 and a higher percentage of patients with detectable viral load in patients on ZDV compared to those on EFV (Table 2). Overall, 32% patients on ZDV and 6% patients on EFV switched to another regimen during the first six months (Figure 1).


Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.

Ouattara E, Danel C, Moh R, Gabillard D, Peytavin G, Konan R, Carrou JL, Bohoussou F, Eholie SP, Anglaret X - J Int AIDS Soc (2013)

Early drug discontinuation and viral load suppression at six months in patients who started ART with TDF-FTC-EFV or TDF-FTC-ZDV. LTFU: lost-to-follow-up; M6: Month-6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643089&req=5

Figure 0001: Early drug discontinuation and viral load suppression at six months in patients who started ART with TDF-FTC-EFV or TDF-FTC-ZDV. LTFU: lost-to-follow-up; M6: Month-6.
Mentions: At the Month-1 visit, a higher percentage of patients on ZDV reported having interrupted their treatment for more than seven days and/or having missed at least one pill during the past four days (Table 2). At the Month-6 visit, there was a trend towards a lower gain in CD4 and a higher percentage of patients with detectable viral load in patients on ZDV compared to those on EFV (Table 2). Overall, 32% patients on ZDV and 6% patients on EFV switched to another regimen during the first six months (Figure 1).

Bottom Line: Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal.We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire.NCT00495651.

View Article: PubMed Central - PubMed

Affiliation: Programme PACCI, Abidjan, Côte d'Ivoire; Univ. Bordeaux, ISPED, F-33000 Bordeaux, France.

ABSTRACT

Introduction: Tenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.

Methods: Participants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3-4 AEs or persistent grade 1-2 AEs leading to drug discontinuation.

Results: A total of 197 patients (76% women, median CD4 count 395/mm(3)) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In-patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1-4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.

Conclusions: We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub-Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in-patients taking other drug regimens.

Clinical trial number: NCT00495651.

Show MeSH
Related in: MedlinePlus