Date Published: July 31, 2017
Publisher: Public Library of Science
Author(s): Lúcia Mabalane Chambal, Eduardo Samo Gudo, Awa Carimo, Rita Corte Real, Nédio Mabunda, Cremildo Maueia, Adolfo Vubil, Ana Flora Zicai, Nilesh Bhatt, Francisco Antunes, Jason Blackard.
HIV/ HBV coinfected patients are at high risk of developing chronic HBV infection, liver cirrhosis and hepatocellular carcinoma. In Mozambique, where HIV prevalence is one of the highest in the world, HIV-infected patients are scarcely characterized in terms of HBV coinfection and 3TC-resistance mutations profile.
To characterize ART-naïve HIV-infected adults, with and without HBV coinfection, a cross-sectional study was conducted between May and November 2012 in two health centers from Maputo city, Mozambique. Subjects were consecutively enrolled in the study and, then, tested for hepatitis B surface antigen (HBsAg). Moreover, CD4+ T cells count, HBV DNA in plasma, HBV genotyping and 3TC-resistance mutations profile of HBV were assessed in HIV/HBV coinfected patients.
In total, 518 patients were enrolled in the study. The median age was 33 years old and 66.8% were women. The median CD4+ T cells count was 361 cells/mm3 and 47 (9.1%) were coinfected with HBV. Out of 46 coinfected patients, 24 (55.2%) had HBV DNA ≥ 20 – < 20 000 and 12 (26.1%) had HBV-DNA ≥20 000. APRI > 2.0 was reported in 4.3% of coinfected and 1.7% of monoinfected patients (p = 0.228), while FIB-4 > 3.25 was reported in 4.4% of coinfected and 1.3% of monoinfected patients (p = 0.112). Genotype A was the most frequent, identified in 25/27 (92.6%) patients, whereas genotype E was present in 2/27 (7.4%) patients. No patient had 3TC-resistance mutations.
This study showed that HBV coinfection was prevalent among ART-naïve HIV-infected adults in Mozambique. Overall, these data highlight the importance of screening HBV coinfection as an integrated measure of HIV routine care to improve health conditions and treatment of HIV/HBV coinfected patients.
Human immunodeficiency virus (HIV) infection is a major public health problem in sub-Saharan Africa, where it is estimated to live 2/3 of the 34 million people globally infected with HIV . In the last decade, coinfection with hepatitis B virus (HBV) became a serious concern among HIV-infected patients, because both viruses share similar routes of infection. In addition, data from Western cohorts show that HIV impacts on almost every aspect of the natural history of HBV infection [2, 3]. Among the worldwide HIV-infected individuals, 5–15% are estimated to be coinfected with HBV [2, 4–6]. Consequences include higher rates of chronicity after acute HBV infection, higher level of HBV replication, more rapid progression of liver disease, higher liver-related mortality, and increased risk of hepatotoxicity to antiretroviral drugs [7–12]. Also in Western cohorts, liver disease has emerged as a leading cause of death in HIV-infected individuals coinfected with either hepatitis B or C [12–15]. Recent studies found that coinfection with HBV can also lead to increased progression in outcomes related to Acquired Immune Deficiency Syndrome (AIDS) and all-cause mortality among HIV-infected patients [16, 17]. Moreover, the burden of coinfection is greater in limited resources regions, such as the sub-Saharan Africa [2, 4–6]. Recently, HIV/HBV coinfection in sub-Saharan Africa has received medical attention, as almost all African countries are scaling up their antiretroviral (ARV) therapy (ART) programs towards the ambitious target of universal coverage and elimination of HIV transmission [18–20]. Despite the World Health Organization (WHO) recommendations to test hepatitis B surface antigen (HBsAg) in all HIV-infected patients , this testing is rarely performed in sub-Saharan Africa, due to its unavailability. Additionally, based on WHO guidelines, patients with HIV/HBV coinfection should start ART regimen with at least two active drugs for HBV infection, such as tenofovir (TDF) with emtricitabine (FTC) or lamivudine (3TC). As a result of the rapid growth of ART programs in sub-Saharan Africa and of the unknown status for HBV infection, when the therapy starts, a general concern has been raised about HBV mutations causing 3TC-resistance [22–24]. In spite of this, data regarding the primary resistance of HBV to 3TC in Southern African countries is still insufficient. For instance, Mozambique has the eighth highest HIV prevalence in the world and the prevalence of HIV/HBV coinfection is 13.6% [1, 25–27]. In this country, 3TC and TDF are currently available in the national program for HIV treatment and are recommended in HIV/HBV coinfected patients. However, no national guidelines for screening and treatment of HBV infection are available and liver disease monitoring is not performed routinely, within the national health system.
Between May and November 2012, a cross-sectional study was conducted in two health centers from the suburban area of Maputo city, Mozambique. Both sites provide primary health care services to HIV-infected individuals in outpatient settings. This local belongs to a large suburban area of Maputo city known for its poverty and high population density, associated with precarious housing, low literacy and income (informal labor) and poor sanitation.
In this study, 518 ART-naïve HIV-infected patients were enrolled. The median age of the study population was 33 years old (interquartile range [IQR]: 28–42 years) and 66.8% were women. HBsAg was reactive in 47 patients, yielding a coinfection rate of 9.1%.
To the best of our knowledge, this represents the first study addressing clinical and laboratory characteristics of HIV/HBV coinfection, HBV DNA viral load, and profile of HBV resistance to 3TC in southern Mozambique. The burden of HIV-infection in this region is the heaviest over the country. The prevalence of coinfection was determined to be 9.1%, which was slightly lower than previously reported in the region [25, 27]. However, the obtained prevalence in southern Mozambique was superior to the values reported in the northern region , and in other countries from sub-Saharan Africa [24, 37–39]. Mozambique is estimated to have more than 1.5 million people living with HIV infection [1, 26]. Based on the current literature and in our study, we anticipate that approximately 150,000 people might be coinfected with HIV/ HBV. Thus, intervening in those cases is a major concern, as coinfected patients are at higher risk of developing liver toxicity to ART, cirrhosis, hepatocelular carcinoma (HCC) and death [40, 41]. In this study, we quantified HBV DNA levels in plasma of HIV/HBV coinfected patients, since this parameter is considered a strong predictor of liver-related diseases (e.g., cirrhosis and HCC) [12, 42, 43]. Indeed, our data showed that 26.1% of the coinfected patients had a HBV viral load >20,000 UI/mL. This finding is in line with what was found in another study conducted in developing countries, where a significant proportion of HIV/HBV coinfected patients present HBV DNA≥ 20,000 IU/mL .
This study strengthens the knowledge on HIV/HBV coinfection in Mozambique and also allowed to characterize this new cohort in Maputo City. We found that one third of HIV/HBV coinfected patients presents high levels of HBV DNA and are at risk of developing a liver-related disease. This finding raises a serious public health concern, which highlights the need to identify HIV/HBV coinfection in these populations. Finally, this study reinforces the importance of integrating HBV screening programs into HIV routine care to reduce morbidity and mortality levels caused by HIV/HBV coinfection.