Long-term Subcutaneous Tissue Changes Among Antiretroviral-Naive Persons
Long-term Subcutaneous Tissue Changes Among Antiretroviral-Naive Persons
Objectives: To assess long-term changes in subcutaneous tissue among antiretroviral-naive persons initiating 1 of 3 nucleoside reverse transcriptase inhibitor (NRTI)-containing regimens.
Methods: We compared changes in 308 participants initiating stavudine plus lamivudine (d4T+3TC; N = 63), zidovudine plus lamivudine (ZDV+3TC; N = 192), and abacavir plus lamivudine (ABC+3TC; N = 53), along with protease inhibitors and/or non-NRTIs. Anthropometric measurements (skinfolds) were performed at baseline and 4-month intervals. Rates of change (mm/y) over 36 months, for the early period (months 4 through 12) and late period (months 16 through 36), were calculated.
Results: The rates were negative (tissue loss) for the abdomen and thigh (d4T+3TC, ZDV+3TC) and triceps (ZDV+3TC) skinfolds. For ABC+3TC, most rates were positive (tissue gain). No differences among regimens were seen for the rates of change in the subscapular or suprascapular skinfolds. Rates in the early period were generally positive. The late period rates were negative for d4T+3TC and ZDV+3TC and significantly different from 0 for the abdomen and thigh (d4T+3TC, ZDV+3TC) and triceps (ZDV+3TC) skinfolds, whereas ABC+3TC had less loss in the late period. Most early versus late differences were significant for d4T+3TC and ZDV+3TC; only the triceps skinfold was significant for ABC+3TC.
Conclusions: In this prospective nonrandomized evaluation, subcutaneous tissue changes varied by regimen. Similar losses were demonstrated for d4T+3TC and ZDV+3TC, whereas ABC+3TC had gains. Temporal differences in rates for d4T+3TC and ZDV+3TC suggest initial recovery followed by long-term treatment effect.
Multiple lines of evidence have implicated certain nucleoside reverse transcriptase inhibitors (NRTIs) in the development of lipoatrophy, with associations identified with cumulative duration of NRTI exposure and the current use of thymidine analogues, particularly stavudine (d4T). Insufficient information is available comparing long-term regional body composition changes with the use of thymidine analogue-sparing regimens to those with thymidine analogue-containing regimens. This comparison is clinically important in antiretroviral-naive patients, because recent results have demonstrated a modest improvement in fat mass among patients changing from a thymidine analogue-containing regimen to a thymidine analogue-sparing regimen.
The prevalence of HIV-related lipodystrophy has varied as a result of different methods for assessing and defining lipodsytrophy. Recent studies have demonstrated regional differences in the morphologic changes associated with HIV infection, with the predominant changes being peripheral and central lipoatrophy affecting subcutaneous fat. Many of these studies use dual-energy x-ray absorptiometry (DEXA) scanning, which is not able to assess specific types of regional fat changes, or the studies have used costly radiologic tests (eg, computed tomography [CT], magnetic resonance imaging [MRI]). Furthermore, none of the studies have assessed how initiation of specific antiretroviral therapy (ART) regimens affects long-term regional subcutaneous tissue. Thus, the purpose of this study was to assess the long-term changes in subcutaneous tissue among ART-naive persons initiating 1 of 3 NRTI-containing regimens: d4T plus lamivudine (d4T+3TC) versus zidovudine plus lamivudine (ZDV+3TC) versus abacavir plus lamivudine (ABC+3TC).
Objectives: To assess long-term changes in subcutaneous tissue among antiretroviral-naive persons initiating 1 of 3 nucleoside reverse transcriptase inhibitor (NRTI)-containing regimens.
Methods: We compared changes in 308 participants initiating stavudine plus lamivudine (d4T+3TC; N = 63), zidovudine plus lamivudine (ZDV+3TC; N = 192), and abacavir plus lamivudine (ABC+3TC; N = 53), along with protease inhibitors and/or non-NRTIs. Anthropometric measurements (skinfolds) were performed at baseline and 4-month intervals. Rates of change (mm/y) over 36 months, for the early period (months 4 through 12) and late period (months 16 through 36), were calculated.
Results: The rates were negative (tissue loss) for the abdomen and thigh (d4T+3TC, ZDV+3TC) and triceps (ZDV+3TC) skinfolds. For ABC+3TC, most rates were positive (tissue gain). No differences among regimens were seen for the rates of change in the subscapular or suprascapular skinfolds. Rates in the early period were generally positive. The late period rates were negative for d4T+3TC and ZDV+3TC and significantly different from 0 for the abdomen and thigh (d4T+3TC, ZDV+3TC) and triceps (ZDV+3TC) skinfolds, whereas ABC+3TC had less loss in the late period. Most early versus late differences were significant for d4T+3TC and ZDV+3TC; only the triceps skinfold was significant for ABC+3TC.
Conclusions: In this prospective nonrandomized evaluation, subcutaneous tissue changes varied by regimen. Similar losses were demonstrated for d4T+3TC and ZDV+3TC, whereas ABC+3TC had gains. Temporal differences in rates for d4T+3TC and ZDV+3TC suggest initial recovery followed by long-term treatment effect.
Multiple lines of evidence have implicated certain nucleoside reverse transcriptase inhibitors (NRTIs) in the development of lipoatrophy, with associations identified with cumulative duration of NRTI exposure and the current use of thymidine analogues, particularly stavudine (d4T). Insufficient information is available comparing long-term regional body composition changes with the use of thymidine analogue-sparing regimens to those with thymidine analogue-containing regimens. This comparison is clinically important in antiretroviral-naive patients, because recent results have demonstrated a modest improvement in fat mass among patients changing from a thymidine analogue-containing regimen to a thymidine analogue-sparing regimen.
The prevalence of HIV-related lipodystrophy has varied as a result of different methods for assessing and defining lipodsytrophy. Recent studies have demonstrated regional differences in the morphologic changes associated with HIV infection, with the predominant changes being peripheral and central lipoatrophy affecting subcutaneous fat. Many of these studies use dual-energy x-ray absorptiometry (DEXA) scanning, which is not able to assess specific types of regional fat changes, or the studies have used costly radiologic tests (eg, computed tomography [CT], magnetic resonance imaging [MRI]). Furthermore, none of the studies have assessed how initiation of specific antiretroviral therapy (ART) regimens affects long-term regional subcutaneous tissue. Thus, the purpose of this study was to assess the long-term changes in subcutaneous tissue among ART-naive persons initiating 1 of 3 NRTI-containing regimens: d4T plus lamivudine (d4T+3TC) versus zidovudine plus lamivudine (ZDV+3TC) versus abacavir plus lamivudine (ABC+3TC).