Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort

Abstract

Objective: To understand the HIV-hepatitis B virus (HBV) epidemic from a global perspective by clinically and virologically characterizing these viruses at the time of antiretroviral therapy (ART) initiation in a multinational cohort.

Methods and design: HIV-infected patients enrolled in two international studies were classified as HIV-HBV coinfected or HIV monoinfected prior to ART. HIV-HBV coinfected patients were tested for HBV characteristics, hepatitis D virus (HDV), a novel noninvasive marker of liver disease, and drug-resistant HBV. Comparisons between discrete covariates used χ or Fisher's exact tests (and Jonchkheere-Terpstra for trend tests), whereas continuous covariates were compared using Wilcoxon Rank-Sum Test.

Results: Of the 2105 HIV-infected patients from 11 countries, the median age was 34 years and 63% were black. The 115 HIV-HBV coinfected patients had significantly higher alanine aminotransferase and aspartate aminotransferase values, lower BMI, and lower CD4 T-cell counts than HIV monoinfected patients (median 159 and 137 cells/μl, respectively, P = 0.04). In the coinfected patients, 49.6% had HBeAg-negative HBV, 60.2% had genotype A HBV, and 13% were HDV positive. Of the HBeAg-negative patients, 66% had HBV DNA 2000 IU/ml or less compared to 5.2% of the HBeAg-positive individuals. Drug-resistant HBV was not detected.

Conclusion: Screening for HBV in HIV-infected patients in resource-limited settings is important because it is associated with lower CD4 T-cell counts. In settings in which HBV DNA is not available, HBeAg may be useful to assess the need for HBV treatment. Screening for drug-resistant HBV is not needed prior to starting ART in settings in which this study was conducted.

Figure 1

Distribution of HBV prevalence and mean CD4+ T-cell count by country. There is no clear relationship between HBV prevalence and mean CD4+ T-cell count.

Figure 2

Figure 2a. Univariable linear regression models with log HBV DNA as the outcome. HBeAg positive status was associated with a 3.63 log IU/ml higher HBV DNA, anti-HBe positive status was associated with a 2.87 log IU/ml lower HBV DNA, both ALT and AST were associated with higher HBV DNA levels, and non-A genotype HBV was associated with higher HBV DNA levels. Figure 2b. Multivariable linear regression models with log HBV DNA as the outcome. The associated variables from the univariable models were included in this model and CD4 count was forced into the model. Anti-HBe was not included since it is collinear with HBeAg status. HBeAg-positive status was associated with a significantly higher HBV DNA level (3.35 log IU/ml higher compared to HBeAg-negative subjects). AST was also associated with higher HBV DNA level.

Figure 2

Figure 2a. Univariable linear regression models with log HBV DNA as the outcome. HBeAg positive status was associated with a 3.63 log IU/ml higher HBV DNA, anti-HBe positive status was associated with a 2.87 log IU/ml lower HBV DNA, both ALT and AST were associated with higher HBV DNA levels, and non-A genotype HBV was associated with higher HBV DNA levels. Figure 2b. Multivariable linear regression models with log HBV DNA as the outcome. The associated variables from the univariable models were included in this model and CD4 count was forced into the model. Anti-HBe was not included since it is collinear with HBeAg status. HBeAg-positive status was associated with a significantly higher HBV DNA level (3.35 log IU/ml higher compared to HBeAg-negative subjects). AST was also associated with higher HBV DNA level.

Figure 3

Frequency (in percent) of subjects with HBV DNA >200,000 IU/ml by CD4+ T-cell category. Subjects with CD4 T-cells <50 cells/mm³ had the highest proportion with HBV DNA >200, 000 IU/ml.