Of the 2,791 HIV+ women in WIHS, 2,702 (97%) had HCV serology results (). Of those 2,702 women, 18 (0.7%) were missing baseline serum creatinine measurement and were also excluded from the analysis, leaving a final study population of 2,684 women. Women who were missing HCV serology or baseline serum creatinine (n=107, or 3.8% of the the original 2,791) were slightly older (mean age (±SD): 37(±8) v. 35(±8), p-value=0.008)) and more likely to use injection drugs (47 v. 33%, p-value=0.002) and were less likely to be on HAART at baseline (8% v. 14%, p-value=0.02). However, there were no significant differences in mean ALT, serum creatinine, or the proportion with eGFR<60 mL/min/1.73m2 between the women who were and were not excluded for missing data.
Flowchart of Study Population Selection
Of the 2,684 women in the final cohort, 945 (35%) were HCV seropositive. HIV/HCV co-infected women were more likely to be older, African American, poor, and drug users at baseline, and were less likely to report being on HAART (). Among the women with eGFR ≥60mL/min/1.73m2, those who were HCV seropositive were more likely to have a higher HIV viral load, have had an AIDS-defining illness, and have hypertension. Diabetes was not significantly more common among women with HCV. At baseline, 180 (6.7%) of the women in the sample had an eGFR<60mL/min/1.73m2. At baseline there was a higher prevalence of CKD among women who were HCV seropositive: 9.8% (93/945) versus 5% (87/1,739) (p-value<0.01). Before adjustment, women with HCV appeared to be twice as likely to have prevalent CKD based on eGFR (unadjusted OR=2.07 [95% CI: 1.53 to 2.81]; p-value<0.001). After adjustment for age, the relative odds was attenuated to 1.47 (95% CI: 1.07 to 2.01, p-value=0.017), and after full adjustment for all the covariates (age, African American ethnicity, education, low income, diabetes, hypertension, AIDS, CD4 cell count, log HIV viral load, HAART, use of renal toxic medications, injections drug use and any illegal drug use) the estimate was further attenuated and no longer significant (OR=1.35 [95% CI: 0.93 to 1.97], p-value=0.11).
Baseline Characteristics of Sample Population by Estimated Glomerular Filtration Rate and HCV Status
The median follow-up time was 4.8 years (first and third quartiles: 3.5, 11 years) for women without CKD at baseline (based on eGFR), 4.5 years (first and third quartiles: 1, 11) for women with CKD. The median number of creatinine measurements was 9 (first and third quartiles: 4, 16) for women without baseline CKD, 6 (first and third quartiles: 2, 14) for women with CKD. There were no missing follow-up creatinine data for 2,429 (91%) of the women in the study; 100 (3%) were missing only one measurement, 155 (4%) were missing ≥2 measurements. The linear mixed models allowed for differing numbers of observations across participants arising from missed visits.
Based on calculation of individual slopes from the linear mixed models, the majority of HIV infected women had either improvement or no change, or only mildly decreased eGFR over time, regardless of HCV status (). However, the women who were also HCV seropositive were more likely to experience a decline in eGFR over time, and experience higher rates of decline.
Distribution of Rates of eGFR Decline by HCV Status (Based on Estimated Individual Slopes)
In the combined data, we found that the effect of HCV on net decline in eGFR differed significantly by baseline eGFR status, so the linear mixed model analyses were stratified by eGFR <60 mL/min/1.73m2. Among the women with CKD at baseline, HCV seropositivity was statistically significantly associated with a net decrease in eGFR of 5.6% per year after adjustment for other covariates (). This effect was greater than the effect observed for hypertension, and slightly less than the effect for diabetes. In contrast, for women with a baseline eGFR ≥60 mL/min/1.73m2, HCV did not appear to have a significant effect in change in eGFR over time. Results from the sensitivity analysis using an interaction term for HCV and eGFR as a continuous variable (as opposed to dichotomous) were also significant.
Longitudinal Differences in eGFR Associated with HCV and Other Covariates (Results of the Fully Adjusted Linear Mixed Models)a