HIV Outcomes in HBV Coinfected Individuals on HAART
HIV Outcomes in HBV Coinfected Individuals on HAART
Of 5403 HIV-positive participants enrolled in the NHS with a documented HIV-positive date, 2797 were ever on HAART (after 1996), 2536 (81%) had HBV testing results available to determine HB status in the HIW and were included in these analyses. Individuals whose HB status were not classified differed from those who were in that they were older at HAART start, had a greater percentage of HCV seropositivity, had a longer duration of HIV before HI, were more often diagnosed in the pre-HAART era and had lower CD4 nadirs (data not shown). HB status at HI was classified as HB negative (n = 1505; 66%), resolved HB (n = 518; 23%), isolated HBcAb (n = 139; 6%), or chronic HB (n = 131; 6%). Characteristics at the time of HI by HB status are shown in Table 1 . Age at HIV diagnosis and HI [overall median, 29 years; interquartile range (IQR), 24–35 and 33 years; IQR, 28–39, respectively] were significantly different among the 4 HB groups, with HB-negative individuals diagnosed with HIV in the later calendar years, initiating HAART at the youngest age, having the lowest number of individuals with previous AIDS, having the least number with previous ART use, and having the highest median CD4 count at HI. Isolated core subjects had the highest proportion of HCV (15%). The chronic HB group had the lowest median CD4 at HI (median, 278; IQR, 146–410), and highest alanine aminotransferase values (median, 59 IU/L; IQR, 33–102). HIV RNA levels at the time of HI were available for 2005 (87%) participants and were similar among the groups (median, 4.5 log10 copies/mL; IQR, 3.8–5). Median follow-up was 9.2 years; IQR, 4.4–16. Of all subjects, 93% received HBV-active HAART regimens at HI. Of individuals initiating HAART between 1996 and 1999, the majority were on unboosted PIs (78%); however, from 2000 to 2012, 68% were on an NNRTI regimen (data not shown).
In unadjusted analyses by HB status, HB status was associated with HIV VS in the first 6 months and 1 year (data not shown). Within 6 months, VS rates for 1015 subjects were 53% overall, with HB negative, chronic HB, isolate core, and resolved HB achieving rates of 58%, 35%, 44%, and 45%, respectively, P < 0.001. Within 1 year, VS rates for 1250 subjects were 59% overall, with HB negative, chronic HB, isolate core, and resolved HB achieving rates of 65%, 40%, 53%, and 47%, respectively, P < 0.001. Table 2 presents the adjusted OR for achieving HIV VS within 6 months and 1 year of HI for the 4 HB groups. The number of subjects included in models 1 (6 months) and 2 (12 months) were 1922 and 2130 subjects, respectively. The adjusted OR for achieving VS was not significantly different by HB status, whereas age, year of HI, VL at HI, previous ART, and HIV VL assay count were significantly associated with the OR for achieving VS within 6 months and 12 months of HI, and African American race was significantly associated with achieving VS within 12 months of HI. HB status at HI, gender, HCV status at HI, CD4 count at HI, and AIDS before HI were not predictive of VS.
In an unadjusted model, over 5533 years of follow-up, there were 863 events of VF. The rate of VF was 15.6 events/100 PY; 95% CI: 14.6 to 16.7 overall. VF by HBV status was higher in the chronic HB status group (23.5 events/100 PY; 95% CI: 17.9 to 30.3) over the years of follow-up as compared with the isolated, resolved, and HB-negative status groups (18.8 events per 100 PY; 95% CI: 14.4 to 24, 18.5 events per 100 PY; 95% CI: 16.3 to 21, and 13.7 events per 100 PY; 95% CI: 12.6 to 15, respectively) (data not shown). Predictors of VF in adjusted analyses, however, did not show a significant difference by HB status, suggesting the association was confounded by other factors ( Table 3 ). Younger age, African American race, HI in the period 1996–1999, and previous ART were significantly associated with an increased risk of VF. Higher VL at HI showed a trend toward increased risk of VF (HR = 1.09; 95% CI: 1.00 to 1.18).
Unadjusted trends in CD4 reconstitution by HBV status are shown in Figure 1. CD4 slope did not significantly differ by HB status during the first 6 months after HI (chronic: P = 0.838; isolated core: P = 0.270; resolved HB: P = 0.239) ( Table 4 ). The rate increase in CD4 cell count in chronic HB compared with HB negatives during the period between 6 months and 4 years after HI was also not significantly different (chronic: P = 0.069; isolated core: P= 0.289; resolved HB: P = 0.099). A significantly greater rate increase in CD4 cell count in chronic HB compared with HB negative, however, was seen during the period from 4 to 12 years after HI (chronic: P < 0.001; isolated core: P= 0.841; resolved HB: P = 0.071), after adjustment for age at HI, gender, race, HCV status at HI, AIDS before HI, CD4 cell count at HI, HIV VL at HI, ART before HI, and year of HI.
During 14,458 PY of follow-up (range, January 1996 to February 2010), 269 participants experienced an AIDS event or death after HI. AIDS events occurred at a rate of 1.86 per 100 PY; 95% CI: 1.64 to 2.10. In multivariate analysis, chronic HB status and resolved HB status were significantly associated with an increased risk of AIDS or death (chronic HB; HR = 1.68; 95% CI: 1.05 to 2.68, isolated HB; HR = 1.51; 95% CI: 0.93 to 2.44, resolved HB; HR = 1.61; 95% CI: 1.15 to 2.25). The HR comparing individuals with isolated HBcAb to those who were HB negative was not significant (data not shown). Other covariates that were associated with a significantly increased risk of an AIDS or death included subjects with a positive HCV status (HR = 1.99; 95% CI: 11.26 to 3.16), CD4 cell count at HI <200 (HR 3.70; 95% CI: 2.49 to 5.50) and 200–350 (HR = 1.35; 95% CI: 0.85 to 2.05), as compared with a CD4 cell count ≥350, and previous ART (HR = 2.06; 95% CI: 1.39 to 3.07). All models were stratified by AIDS before HI. The interaction between HBV and HCV was not significant.
Results
Of 5403 HIV-positive participants enrolled in the NHS with a documented HIV-positive date, 2797 were ever on HAART (after 1996), 2536 (81%) had HBV testing results available to determine HB status in the HIW and were included in these analyses. Individuals whose HB status were not classified differed from those who were in that they were older at HAART start, had a greater percentage of HCV seropositivity, had a longer duration of HIV before HI, were more often diagnosed in the pre-HAART era and had lower CD4 nadirs (data not shown). HB status at HI was classified as HB negative (n = 1505; 66%), resolved HB (n = 518; 23%), isolated HBcAb (n = 139; 6%), or chronic HB (n = 131; 6%). Characteristics at the time of HI by HB status are shown in Table 1 . Age at HIV diagnosis and HI [overall median, 29 years; interquartile range (IQR), 24–35 and 33 years; IQR, 28–39, respectively] were significantly different among the 4 HB groups, with HB-negative individuals diagnosed with HIV in the later calendar years, initiating HAART at the youngest age, having the lowest number of individuals with previous AIDS, having the least number with previous ART use, and having the highest median CD4 count at HI. Isolated core subjects had the highest proportion of HCV (15%). The chronic HB group had the lowest median CD4 at HI (median, 278; IQR, 146–410), and highest alanine aminotransferase values (median, 59 IU/L; IQR, 33–102). HIV RNA levels at the time of HI were available for 2005 (87%) participants and were similar among the groups (median, 4.5 log10 copies/mL; IQR, 3.8–5). Median follow-up was 9.2 years; IQR, 4.4–16. Of all subjects, 93% received HBV-active HAART regimens at HI. Of individuals initiating HAART between 1996 and 1999, the majority were on unboosted PIs (78%); however, from 2000 to 2012, 68% were on an NNRTI regimen (data not shown).
HIV Virologic Suppression
In unadjusted analyses by HB status, HB status was associated with HIV VS in the first 6 months and 1 year (data not shown). Within 6 months, VS rates for 1015 subjects were 53% overall, with HB negative, chronic HB, isolate core, and resolved HB achieving rates of 58%, 35%, 44%, and 45%, respectively, P < 0.001. Within 1 year, VS rates for 1250 subjects were 59% overall, with HB negative, chronic HB, isolate core, and resolved HB achieving rates of 65%, 40%, 53%, and 47%, respectively, P < 0.001. Table 2 presents the adjusted OR for achieving HIV VS within 6 months and 1 year of HI for the 4 HB groups. The number of subjects included in models 1 (6 months) and 2 (12 months) were 1922 and 2130 subjects, respectively. The adjusted OR for achieving VS was not significantly different by HB status, whereas age, year of HI, VL at HI, previous ART, and HIV VL assay count were significantly associated with the OR for achieving VS within 6 months and 12 months of HI, and African American race was significantly associated with achieving VS within 12 months of HI. HB status at HI, gender, HCV status at HI, CD4 count at HI, and AIDS before HI were not predictive of VS.
In an unadjusted model, over 5533 years of follow-up, there were 863 events of VF. The rate of VF was 15.6 events/100 PY; 95% CI: 14.6 to 16.7 overall. VF by HBV status was higher in the chronic HB status group (23.5 events/100 PY; 95% CI: 17.9 to 30.3) over the years of follow-up as compared with the isolated, resolved, and HB-negative status groups (18.8 events per 100 PY; 95% CI: 14.4 to 24, 18.5 events per 100 PY; 95% CI: 16.3 to 21, and 13.7 events per 100 PY; 95% CI: 12.6 to 15, respectively) (data not shown). Predictors of VF in adjusted analyses, however, did not show a significant difference by HB status, suggesting the association was confounded by other factors ( Table 3 ). Younger age, African American race, HI in the period 1996–1999, and previous ART were significantly associated with an increased risk of VF. Higher VL at HI showed a trend toward increased risk of VF (HR = 1.09; 95% CI: 1.00 to 1.18).
CD4 Recovery
Unadjusted trends in CD4 reconstitution by HBV status are shown in Figure 1. CD4 slope did not significantly differ by HB status during the first 6 months after HI (chronic: P = 0.838; isolated core: P = 0.270; resolved HB: P = 0.239) ( Table 4 ). The rate increase in CD4 cell count in chronic HB compared with HB negatives during the period between 6 months and 4 years after HI was also not significantly different (chronic: P = 0.069; isolated core: P= 0.289; resolved HB: P = 0.099). A significantly greater rate increase in CD4 cell count in chronic HB compared with HB negative, however, was seen during the period from 4 to 12 years after HI (chronic: P < 0.001; isolated core: P= 0.841; resolved HB: P = 0.071), after adjustment for age at HI, gender, race, HCV status at HI, AIDS before HI, CD4 cell count at HI, HIV VL at HI, ART before HI, and year of HI.
Deaths and AIDS-Defining Illnesses
During 14,458 PY of follow-up (range, January 1996 to February 2010), 269 participants experienced an AIDS event or death after HI. AIDS events occurred at a rate of 1.86 per 100 PY; 95% CI: 1.64 to 2.10. In multivariate analysis, chronic HB status and resolved HB status were significantly associated with an increased risk of AIDS or death (chronic HB; HR = 1.68; 95% CI: 1.05 to 2.68, isolated HB; HR = 1.51; 95% CI: 0.93 to 2.44, resolved HB; HR = 1.61; 95% CI: 1.15 to 2.25). The HR comparing individuals with isolated HBcAb to those who were HB negative was not significant (data not shown). Other covariates that were associated with a significantly increased risk of an AIDS or death included subjects with a positive HCV status (HR = 1.99; 95% CI: 11.26 to 3.16), CD4 cell count at HI <200 (HR 3.70; 95% CI: 2.49 to 5.50) and 200–350 (HR = 1.35; 95% CI: 0.85 to 2.05), as compared with a CD4 cell count ≥350, and previous ART (HR = 2.06; 95% CI: 1.39 to 3.07). All models were stratified by AIDS before HI. The interaction between HBV and HCV was not significant.