Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss.
BACKGROUND
Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.


RESULTS
Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial. Randomisation was between zidovudine-containing therapy (zidovudine/lamivudine+lopinavir/ritonavir) and zidovudine-sparing therapy (nevirapine+lopinavir/ritonavir). Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3, 12, 24 months of antiretroviral therapy. In the zidovudine/lamivudine+lopinavir/ritonavir group, from 3 months onward limb fat decreased progressively by 684+/-293 grams (estimated mean+/-standard error of the mean)(p = 0.02) up to 24 months whereas abdominal fat increased, but exclusively in the visceral compartment (+21.9+/-8.1 cm(2), p = 0.008)). In contrast, in the nevirapine+lopinavir/ritonavir group, a generalized increase in fat mass was observed. After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups, but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group (6.1+/-0.2 versus 5.3+/-0.2 and 3.6+/-0.1 versus 2.8+/-0.1 mmol/l respectively, p<0.05). Virologic response and safety were comparable in both groups.


CONCLUSIONS
Zidovudine/lamivudine+lopinavir/ritonavir, but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients, is associated with lipoatrophy and greater relative intraabdominal lipohypertrophy, suggesting that zidovudine/lamivudine contributes to both these features of lipodystrophy. These findings support to no longer consider zidovudine/lamivudine as one of the preferred possible components of first-line antiretroviral therapy where alternative treatments are available.


BACKGROUND
ClinicalTrials.gov NCT 00122226.
van Vonderen
Marit G A
MG
Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. M.vVonderen@vumc.nl
van Agtmael
Michiel A
MA
Hassink
Elly A M
EA
Milinkovic
Ana
A
Brinkman
Kees
K
Geerlings
Suzanne E
SE
Ristola
Matti
M
van Eeden
Arne
A
Danner
Sven A
SA
Reiss
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008060:Lipodystrophy / Q000139:chemically induced* / Q000150:complications* / Q000821:virology; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000097:blood; D015215:Zidovudine / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015415:Biomarkers; D008055:Lipids; D011744:Pyrimidinones; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D005947:Glucose