Search
Close
Search
Advanced Search
Search Menu
AI Discovery Assistant

To the Editor—We read with interest the informative article by Kouamé et al describing mortality in human immunodeficiency virus (HIV)/hepatitis B virus (HBV)-coinfected patients on antiretroviral therapy (ART) in West Africa [1]. In line with studies from high-income countries, the results from the Temprano trial show that active HBV infection increases mortality among HIV-infected individuals [2]. However, clinical trial data cannot be generalized to other clinical settings in sub-Saharan Africa (SSA), where resources for patient monitoring and management are limited and patients who initiate ART often present with advanced stages of disease. Real-life data on the impact of HBV determinants on mortality from primary HIV care settings in SSA are scarce.

Since January 2013, we recruited consecutive HIV-infected patients at time of ART initiation into a prospective cohort in Lusaka, Zambia, and Ancuabe, a rural area in Mozambique, within the IeDEA collaboration [3]. All patients were tested for the presence of chronic HBV infection, defined as a positive HBsAg rapid test (Determine®, Alere, Yavne, Israel), and HBV viral load (VL) was measured in HIV/HBV-coinfected individuals using quantitative real-time polymerase chain reaction (Roche, Indianapolis, Indiana) from plasma or dried blood spots [4]. The systematic tracing of patients lost to follow-up (LTFU; i.e., >3 months without a clinical visit) during the first year of ART was performed by phone calls or home visits. We used multivariable Cox proportional hazards methods to compare 1-year mortality between HBV-infected and uninfected patients.

Fourteen percent (276/1948) of the study participants were HBsAg-positive, of whom 137 (49.6%) had an HBV VL above 2000 IU/mL. Median age was 32 years (interquartile range [IQR] 26–40 years), median CD4 count 252 cells/µL (IQR 130–369), 38% had World Health Organization (WHO) stage 3 or 4, and 36% were female. There were no significant differences in CD4 cell counts, body mass index, age, and proportions with advanced HIV disease between groups. HBsAg-positive individuals were more likely to be male (P < .001). After 1 year of ART, 129 (6.6%) patients had died, 113 (5.8%) were LTFU, and 63 (3.2%) transferred or withdrew from the study. One-year mortality was 6.5% (95% confidence interval 5.4–7.8%) in HIV-infected patients, 8.7% (4.9–15.2%) in HIV/HBV-coinfected with HBV VL <2000 IU/mL, and 8.2% (95% CI 4.4–15.2%) in HIV/HBV-coinfected patients with HBV VL >2000 IU/mL. In multivariable analyses, HBsAg-positivity was not associated with mortality (Table 1).

Table 1.
Open in new tab

Risk Factors for 1-Year Mortality, According to Multivariable Cox Proportional Hazard Regression Analyses

Deaths (%)HR (95% CI)P valueaHR (95% CI)P value
HBsAg (%)
 Negative102/1673 (6.1)Ref.Ref.
 Positive27/276 (9.8)1.61 (1.05–2.45).031.21 (0.74–1.98).45
WHO stage (%)
 1 or 250/1203 (4.2)Ref.Ref.
 3 or 479/732 (10.8)2.69 (1.88–3.83)<.0011.42 (0.93–2.17).10
CD4 cell count (%)
 ≥200 cells/µL41/973 (4.2)Ref.Ref.
 <200 cells/µL71/640 (11.1)2.76 (1.88–4.05)<.0012.02 (1.33–3.07).001
BMI (%)
 ≥18.5 kg/m248/1275 (3.8)Ref.Ref.
 <18.5 kg/m267/519 (12.9)3.60 (2.49–5.22)<.0012.66 (1.76–4.02)<.001
Sex (%)
 Female52/1240 (4.2)Ref.Ref.
 Male77/708 (10.9)2.63 (1.85–3.74)<.0011.72 (1.13–2.62).01
Age (%)
 <30 years43/772 (5.6)Ref.Ref.
 ≥30 years86/1176 (7.3)1.29 (0.89–1.85).180.97 (0.63–1.50).89
Deaths (%)HR (95% CI)P valueaHR (95% CI)P value
HBsAg (%)
 Negative102/1673 (6.1)Ref.Ref.
 Positive27/276 (9.8)1.61 (1.05–2.45).031.21 (0.74–1.98).45
WHO stage (%)
 1 or 250/1203 (4.2)Ref.Ref.
 3 or 479/732 (10.8)2.69 (1.88–3.83)<.0011.42 (0.93–2.17).10
CD4 cell count (%)
 ≥200 cells/µL41/973 (4.2)Ref.Ref.
 <200 cells/µL71/640 (11.1)2.76 (1.88–4.05)<.0012.02 (1.33–3.07).001
BMI (%)
 ≥18.5 kg/m248/1275 (3.8)Ref.Ref.
 <18.5 kg/m267/519 (12.9)3.60 (2.49–5.22)<.0012.66 (1.76–4.02)<.001
Sex (%)
 Female52/1240 (4.2)Ref.Ref.
 Male77/708 (10.9)2.63 (1.85–3.74)<.0011.72 (1.13–2.62).01
Age (%)
 <30 years43/772 (5.6)Ref.Ref.
 ≥30 years86/1176 (7.3)1.29 (0.89–1.85).180.97 (0.63–1.50).89

Abbreviations: aHR, adjusted hazard ratio; BMI, body mass index; CI, confidence interval; HBsAg, hepatitis B surface antigen; HR, hazard ratio; WHO, World Health Organization.

Table 1.
Open in new tab

Risk Factors for 1-Year Mortality, According to Multivariable Cox Proportional Hazard Regression Analyses

Deaths (%)HR (95% CI)P valueaHR (95% CI)P value
HBsAg (%)
 Negative102/1673 (6.1)Ref.Ref.
 Positive27/276 (9.8)1.61 (1.05–2.45).031.21 (0.74–1.98).45
WHO stage (%)
 1 or 250/1203 (4.2)Ref.Ref.
 3 or 479/732 (10.8)2.69 (1.88–3.83)<.0011.42 (0.93–2.17).10
CD4 cell count (%)
 ≥200 cells/µL41/973 (4.2)Ref.Ref.
 <200 cells/µL71/640 (11.1)2.76 (1.88–4.05)<.0012.02 (1.33–3.07).001
BMI (%)
 ≥18.5 kg/m248/1275 (3.8)Ref.Ref.
 <18.5 kg/m267/519 (12.9)3.60 (2.49–5.22)<.0012.66 (1.76–4.02)<.001
Sex (%)
 Female52/1240 (4.2)Ref.Ref.
 Male77/708 (10.9)2.63 (1.85–3.74)<.0011.72 (1.13–2.62).01
Age (%)
 <30 years43/772 (5.6)Ref.Ref.
 ≥30 years86/1176 (7.3)1.29 (0.89–1.85).180.97 (0.63–1.50).89
Deaths (%)HR (95% CI)P valueaHR (95% CI)P value
HBsAg (%)
 Negative102/1673 (6.1)Ref.Ref.
 Positive27/276 (9.8)1.61 (1.05–2.45).031.21 (0.74–1.98).45
WHO stage (%)
 1 or 250/1203 (4.2)Ref.Ref.
 3 or 479/732 (10.8)2.69 (1.88–3.83)<.0011.42 (0.93–2.17).10
CD4 cell count (%)
 ≥200 cells/µL41/973 (4.2)Ref.Ref.
 <200 cells/µL71/640 (11.1)2.76 (1.88–4.05)<.0012.02 (1.33–3.07).001
BMI (%)
 ≥18.5 kg/m248/1275 (3.8)Ref.Ref.
 <18.5 kg/m267/519 (12.9)3.60 (2.49–5.22)<.0012.66 (1.76–4.02)<.001
Sex (%)
 Female52/1240 (4.2)Ref.Ref.
 Male77/708 (10.9)2.63 (1.85–3.74)<.0011.72 (1.13–2.62).01
Age (%)
 <30 years43/772 (5.6)Ref.Ref.
 ≥30 years86/1176 (7.3)1.29 (0.89–1.85).180.97 (0.63–1.50).89

Abbreviations: aHR, adjusted hazard ratio; BMI, body mass index; CI, confidence interval; HBsAg, hepatitis B surface antigen; HR, hazard ratio; WHO, World Health Organization.

As opposed to Kouamé et al, we did not find a significant difference in mortality between HIV-infected individuals with active HBV infection and HBV-uninfected ones in southern Africa. We provide robust mortality estimates from primary care clinical settings in SSA, as we limited the risk of underestimating death rates by systematically tracing patients LTFU [5]. Although the burden of liver-related mortality due to HBV infection is high in SSA [6], mortality of patients initiating ART outside of clinical trials remains driven by HIV-associated causes. As low-income countries are starting to implement the “treat all” strategy for HIV infection, the impact of HBV infection on clinical outcomes might become more evident. Therefore, long-term data from cohorts with intensive retention strategies will be crucial to inform monitoring of HIV/HBV-coinfected individuals in the near future.

Notes

Disclaimer. The content is solely the responsibility of the authors and does not represent the official views of the funders.

Funding. This study was supported by the National Institute of Allergy and Infectious Diseases (grant number 5U01-AI069924-05) and Fogarty International Center (grant number 1K01TW009998) of the National Institutes of Health. G. W. was supported by an Ambizione-PROSPER fellowship (PZ00P3_154730) from the Swiss National Science Foundation.

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

1.

Kouamé
GM
,
Boyd
A
,
Moh
R
et al. ;
French National Agency for Research on AIDS and Viral Hepatitis (ANRS) 12136 Temprano and ANRS 12240 VarBVA Study Groups
.
Higher mortality despite early antiretroviral therapy in human immunodeficiency virus and Hepatitis B Virus (HBV)-coinfected patients with high HBV replication
.
Clin Infect Dis
2018
;
66
:
112
–
20
.

Google Scholar

Crossref
Search ADS
PubMed

 
2.

Nikolopoulos
GK
,
Paraskevis
D
,
Hatzitheodorou
E
et al.
Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis
.
Clin Infect Dis
2009
;
48
:
1763
–
71
.

Google Scholar

Crossref
Search ADS
PubMed

 
3.

Egger
M
,
Ekouevi
DK
,
Williams
C
et al.
Cohort Profile: the international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa
.
Int J Epidemiol
2012
;
41
:
1256
–
64
.

Google Scholar

Crossref
Search ADS
PubMed

 
4.

Wandeler
G
,
Musukuma
K
,
Zürcher
S
et al. ;
IeDEA-Southern Africa
.
Hepatitis B infection, viral load and resistance in HIV-infected patients in Mozambique and Zambia
.
PLoS One
2016
;
11
:
e0152043
.

Google Scholar

Crossref
Search ADS
PubMed

 
5.

Brinkhof
MW
,
Pujades-Rodriguez
M
,
Egger
M
.
Mortality of patients lost to follow-up in antiretroviral treatment programmes in resource-limited settings: systematic review and meta-analysis
.
PLoS One
2009
;
4
:
e5790
.

Google Scholar

Crossref
Search ADS
PubMed

 
6.

World Health Organization
.
Global Hepatitis Report 2017
.
Geneva
:
World Health Organization
,
2017
.

Google Scholar

OpenURL Placeholder Text

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Issue Section:
Correspondence
Download all slides