The relative contributions of variables that were highly correlated [i.e. gender and height; body mass index (BMI) and height] were evaluated in nested models. To examine the incremental Nintedanib molecular weight effect of OXPHOS CI and CIV enzyme activity as well as that of mt 8-oxo-dG levels, each was then introduced individually into the previously constructed model. Model selection was based on adjusted R-square and Akaike’s information criterion (AIC). Of the 152 subjects enrolled in SEARCH 003, skin punch biopsies were obtained from 132 subjects who agreed to participate in the neuropathy substudy. All

of these 132 ENFD specimens were judged by the Johns Hopkins Cutaneous Nerve Laboratory as evaluable, and are the focus of this report. All subjects were Thai, with 56.1% recruited from the Thai Red Cross AIDS Research Centre and 43.9% from Queen Savang Vadhana Hospital (Table 1). The gender distribution of 44.7% male is consistent with the gender distribution of the HIV/AIDS epidemic in Thailand. Only a small percentage

of subjects had other common aetiologies for neuropathy (history of isoniazid use, concomitant infection with hepatitis SB203580 C or the presence of diabetes). The median (interquartile range) ENFD (fibres/mm) values prior to initiation of ARV therapy were 21.0 (16.2–26.6) for the distal leg and 31.7 (26.2–40.0) for the proximal thigh. Distal leg ENFD correlated positively with CD4 cell count, and negatively with age, height, log10 plasma HIV RNA, and OXPHOS CI and CIV activity levels (Table 2). The relationships between distal leg ENFD and height, CD4 cell count and OXPHOS CIV are shown graphically in Figure 2. No significant correlations were found with BMI, homeostatic model assessment for insulin resistance (HOMA-IR), fasting glucose, PBMC mtDNA or mt-specific 8-oxo-dG. Women had significantly higher distal

leg natural log (ln) ENFD than men (mean ENFD: women, 24.2 fibres/mm; men, 19.5 fibres/mm; P < 0.01). Proximal thigh ENFD correlated positively with distal leg ENFD. Similar to distal leg ENFD, proximal thigh ENFD correlated positively with CD4 cell count and negatively with height, with no correlations with HOMA-IR, fasting glucose, PBMC mtDNA or mt-specific 8-oxo-dG. Proximal thigh ENFD, however, differed from distal leg ENFD in Rucaparib ic50 showing significant negative correlations with BMI and no correlations with PBMC OXPHOS CI or CIV activity levels. Women had slightly higher proximal thigh ln ENFD than men (mean ENFD: women, 36.0 fibres/mm; men, 31.6 fibres/mm; P = 0.03). Neither distal leg nor proximal thigh ENFD correlated with history of previous ARV medication use during pregnancy or with history of neurotoxic medical comorbidity/medication use (data not shown). The results of the multiple linear regression analyses are shown in Table 3. Simple linear regression analysis showed age, height, CD4 cell count and HIV RNA to each be significantly associated with distal leg ENFD (all P-values < 0.01).