In fact, TAT, and particularly limb fat and SAT, but also VAT and trunk fat, all tended to increase regardless of the regimen, but only significantly so in those randomized to ATV/r. In the CASTLE study, a comparable increase in adipose tissue was observed 96 weeks after starting ritonavir-boosted

ATV [35]. A similar pattern was observed for lean body mass as well as total body mass changes. Early changes in body composition, after cART is first initiated, may at least partially reflect a restoration to normal health. Virological and immunological efficacy was similar in the two arms and therefore do not offer a likely explanation for the difference in body composition changes MLN0128 observed. The higher frequency of low-grade diarrhoea in the SQV/r arm may have contributed to the lower gain in lean body mass and adipose tissue. Another possible explanation is that, for six of the SQV/r-treated patients, but only one ATV/r-treated patient, only baseline and no follow-up DXA and CT scans were obtained. Given that missing values following baseline were imputed using a LOCF approach, this imbalance in available follow-up scans could have contributed to the apparent differences in fat gain INCB024360 between the arms in the ITT analysis, which seems to be supported by the reduced difference observed in the OT analysis of adipose tissue changes. Detrimental effects of SQV on adipocyte differentiation and metabolism

have been reported [36,37]. Whereas ATV by itself has not been clearly demonstrated to affect adipocytes in vitro [38,39], another in vitro study showed that treatment with ritonavir-boosted ATV resulted in decreased adipocyte differentiation and insulin sensitivity, and

promoted oxidative stress and inflammation else [40]. TDF has been associated with nephrotoxicity, the risk of which may be increased by concomitant use of ritonavir-boosted PIs [24,41], potentially by increasing TDF exposure [25]. There is little information about whether this effect differs between PIs. The CASTLE study did not reveal a difference between ATV/r and lopinavir/r, combined with TDF, in the change in eGFR, with only a minor decrease in eGFR in both regimens [42]. The decline in eGFR observed in our study was also minor, developing during the first 12–24 weeks with no changes thereafter, as reported previously [24,41,42]. Only when estimated by CG was the decline in eGFR significantly greater for patients randomized to SQV/r. As the CG (but none of the other estimations) includes weight, the significantly greater increase in weight in ATV/r-treated patients could explain these findings, similar to the suggestions of others [43]. GFR estimated by weight-independent equations such as MDRD or CKD-EPI may offer a more reliable assessment of GFR after the initiation of first-line cART, a period which may be accompanied by significant weight change. Clinically relevant proximal tubulopathy was not observed with either treatment regimen.