**Clinical Management**

**Chapter 4**

**Provisional chapter**

**Human Immunodeficiency Virus-Hepatitis B Virus (HIV-**

The global epidemics of hepatitis B and HIV have led to a new understanding of the complex interactions between these two viruses. Due to similar patterns of contamination, the high prevalence of HBV infection among the 33 million people living with HIV (PLHIV) across the world is about 10%. In highly endemic areas such as sub-Saharan Africa, this prevalence can be as high as 15% and leads us systematically to seek HIV/HBV co-infection. According to WHO, nearly 240 million people are chronically infected with HBV worldwide. Of these, 4 million are co-infected with HIV. Overall, co-infection rates range from 5 to 14% in areas of low prevalence of HBV infection and 5–73% in areas of high prevalence for HBV infection. Studies have revealed the complexity of the infection relationship between HIV and HBV. This complex relationship is thought to be responsible for greater morbidity and mortality of hepatic origin in co-infected patients than in mono-infected individuals. This chapter will highlight the following main points: • Concomitant negative impact of HIV and HBV on their natural histories

• Implication of concomitant negative impact on the overall management of HIV-HBV

The human immunodeficiency virus (HIV) is an enveloped RNA virus (two copies) belonging to the family of Retroviridae, genus Lentivirus. HIV infection and its natural evolution lead

**Keywords:** HIV, HBV, HIV-HBV coinfection, occult hepatitis B infection

**Human Immunodeficiency Virus-Hepatitis B Virus** 

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.78567

**HBV) Coinfection**

**Abstract**

coinfection

**1.1. General information on HIV**

**1. Introduction**

• Treatment and management.

Berthold Bivigou-Mboumba

Berthold Bivigou-Mboumba

**(HIV-HBV) Coinfection**

http://dx.doi.org/10.5772/intechopen.78567

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

#### **Human Immunodeficiency Virus-Hepatitis B Virus (HIV-HBV) Coinfection Human Immunodeficiency Virus-Hepatitis B Virus (HIV-HBV) Coinfection**

DOI: 10.5772/intechopen.78567

Berthold Bivigou-Mboumba Berthold Bivigou-Mboumba

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.78567

#### **Abstract**

The global epidemics of hepatitis B and HIV have led to a new understanding of the complex interactions between these two viruses. Due to similar patterns of contamination, the high prevalence of HBV infection among the 33 million people living with HIV (PLHIV) across the world is about 10%. In highly endemic areas such as sub-Saharan Africa, this prevalence can be as high as 15% and leads us systematically to seek HIV/HBV co-infection. According to WHO, nearly 240 million people are chronically infected with HBV worldwide. Of these, 4 million are co-infected with HIV. Overall, co-infection rates range from 5 to 14% in areas of low prevalence of HBV infection and 5–73% in areas of high prevalence for HBV infection. Studies have revealed the complexity of the infection relationship between HIV and HBV. This complex relationship is thought to be responsible for greater morbidity and mortality of hepatic origin in co-infected patients than in mono-infected individuals. This chapter will highlight the following main points:


**Keywords:** HIV, HBV, HIV-HBV coinfection, occult hepatitis B infection

#### **1. Introduction**

#### **1.1. General information on HIV**

The human immunodeficiency virus (HIV) is an enveloped RNA virus (two copies) belonging to the family of Retroviridae, genus Lentivirus. HIV infection and its natural evolution lead

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

to a set of opportunistic, infectious, or tumoral manifestations, consequences of an immunodepression qualified as acquired immunodeficiency syndrome (AIDS). To date, there are two types of HIV: the first, called HIV-1, is responsible for the pandemic and HIV-2 is more common in West Africa [1].

#### **1.2. Genomic structure and organization**

Morphologically, HIV is a single spherical particle with a diameter ranging from 90 to 120 nm. The virion has a spiky envelope and a dense nucleocapsid, sometimes trapezoidal or bar-shaped.

Structurally it is described as follows (**Figure 1**).

The viral body comprises two identical RNA molecules; three viral enzymes (reverse transcriptase (p66/p51); protease (p10) and integrase (p32)]; and three internal proteins [24 kDa capsid protein (p24); the 7KDa nucleocapsid protein (p7) that is associated with the RNA molecules; and the outermost protein, associated with the viral protease, the 17 kDa matrix protein (p17)].

The viral envelope, emanation of the cellular cytoplasmic membrane, carries two viral glycoproteins (gp) essential in the virus-host cell interaction. This is the gp41 (41 kDa glycoprotein found in the transmembrane position) and the gp120 (120 kDa glycoprotein, lining the outer surface and thus allowing the attachment to its cellular receptor, the CD4 molecule) [1].

The reverse transcriptase (RT) allows the viral genome (RNA) to be retro-transcribed into DNA, thus promoting integration into the chromosomal DNA of the host cell: at this stage, the HIV is called "provirus." In its proviral form, HIV is flanked on both sides by repetitive sequences, strongly implicated in the transcription and integration of the virus. These sequences are called LTR for long terminal repeat and consist of three non-coding regions (U3, R, and U5), allowing the integration of double-stranded DNA into the chromosomal DNA of the host cell. These regions contain, at the 5 'ends of the LTRs, promoters that control the initiation and regulation of viral genome transcription, under the influence of viral and

Human Immunodeficiency Virus-Hepatitis B Virus (HIV-HBV) Coinfection

http://dx.doi.org/10.5772/intechopen.78567

71

In 2015, the number of HIV-related deaths ranged from 930,000 to 1,300,000 worldwide [3]. According to Global AIDS in 2016, approximately, 37 million people live with HIV and 21

The distribution of HIV infection is not equitable in the world, sub-Saharan Africa is the most affected region. In 2015, it alone counted 25,600,000 people living with HIV (PLHIV) or nearly 70% of the world's PLHIV. The overall prevalence in this part of the world is 5.0% (95% CI,

Infection caused by HIV is responsible for the progressive destruction of the immune system, primarily by the removal of CD4 T-cells. These are the targets of the virus to ensure its replication. Lymphocyte homeostasis, which allows proliferation of lymphocyte cells, is gradually becoming ineffective. The immune system thus weakened leads to the appearance of so-called

cellular factors [2].

**1.3. Prevalence of HIV in the world**

**Figure 2.** Genomic organisation of HIV-1 and HIV-2 [2].

4.7–5.2), with 1,900,000 new infections per year.

million are under treatment.

**1.4. Pathophysiology**

HIV has gag, pol, and env as structural genes that encode internal proteins, viral enzymes, and envelope glycoproteins, respectively [2], and it has six regulatory genes: tat, rev, nef, alive, vpr, vpu (for HIV-1), and vpx (for HIV-2) [1] (**Figure 2**).

**Figure 1.** HIV structure (from HIV genetic diversity and its consequences, [1].

**Figure 2.** Genomic organisation of HIV-1 and HIV-2 [2].

to a set of opportunistic, infectious, or tumoral manifestations, consequences of an immunodepression qualified as acquired immunodeficiency syndrome (AIDS). To date, there are two types of HIV: the first, called HIV-1, is responsible for the pandemic and HIV-2 is more

Morphologically, HIV is a single spherical particle with a diameter ranging from 90 to 120 nm. The virion has a spiky envelope and a dense nucleocapsid, sometimes trapezoidal

The viral body comprises two identical RNA molecules; three viral enzymes (reverse transcriptase (p66/p51); protease (p10) and integrase (p32)]; and three internal proteins [24 kDa capsid protein (p24); the 7KDa nucleocapsid protein (p7) that is associated with the RNA molecules; and the outermost protein, associated with the viral protease, the 17 kDa matrix

The viral envelope, emanation of the cellular cytoplasmic membrane, carries two viral glycoproteins (gp) essential in the virus-host cell interaction. This is the gp41 (41 kDa glycoprotein found in the transmembrane position) and the gp120 (120 kDa glycoprotein, lining the outer surface and thus allowing the attachment to its cellular receptor, the CD4 molecule) [1].

HIV has gag, pol, and env as structural genes that encode internal proteins, viral enzymes, and envelope glycoproteins, respectively [2], and it has six regulatory genes: tat, rev, nef,

common in West Africa [1].

70 Advances in HIV and AIDS Control

or bar-shaped.

protein (p17)].

**1.2. Genomic structure and organization**

Structurally it is described as follows (**Figure 1**).

alive, vpr, vpu (for HIV-1), and vpx (for HIV-2) [1] (**Figure 2**).

**Figure 1.** HIV structure (from HIV genetic diversity and its consequences, [1].

The reverse transcriptase (RT) allows the viral genome (RNA) to be retro-transcribed into DNA, thus promoting integration into the chromosomal DNA of the host cell: at this stage, the HIV is called "provirus." In its proviral form, HIV is flanked on both sides by repetitive sequences, strongly implicated in the transcription and integration of the virus. These sequences are called LTR for long terminal repeat and consist of three non-coding regions (U3, R, and U5), allowing the integration of double-stranded DNA into the chromosomal DNA of the host cell. These regions contain, at the 5 'ends of the LTRs, promoters that control the initiation and regulation of viral genome transcription, under the influence of viral and cellular factors [2].

#### **1.3. Prevalence of HIV in the world**

In 2015, the number of HIV-related deaths ranged from 930,000 to 1,300,000 worldwide [3]. According to Global AIDS in 2016, approximately, 37 million people live with HIV and 21 million are under treatment.

The distribution of HIV infection is not equitable in the world, sub-Saharan Africa is the most affected region. In 2015, it alone counted 25,600,000 people living with HIV (PLHIV) or nearly 70% of the world's PLHIV. The overall prevalence in this part of the world is 5.0% (95% CI, 4.7–5.2), with 1,900,000 new infections per year.

#### **1.4. Pathophysiology**

Infection caused by HIV is responsible for the progressive destruction of the immune system, primarily by the removal of CD4 T-cells. These are the targets of the virus to ensure its replication. Lymphocyte homeostasis, which allows proliferation of lymphocyte cells, is gradually becoming ineffective. The immune system thus weakened leads to the appearance of so-called "opportunistic" infections. Eventually, the infected subject dies as a result of this generalized immunosuppression (AIDS stage).

The natural history of HIV infection has been divided into two major phases. The seroconversion stage occurs in the first 6 weeks after infection, a period between the time of infection and the appearance of antibodies. In some patients this phase is accompanied by an influenza state. During this phase, viral replication is intense (every day 1 billion viruses are produced), where viral load levels up to more than 1 million copies per mL of plasma [4], and the patient is very infectious. CD4 T-cell level drops transient but usually returns to baseline.

The chronic phase has two stages.

Asymptomatic phase: This is the clinical latency phase. The immune system continuously destroys the viruses to keep the viral load low (no virological latency). At the same time the CD4 count will gradually decrease. This phase may persist for several years (up to 15 years).

Symptomatic phase: It lasts from a few months to several years. The immune system begins to weaken and no longer effectively controls viral replication. The number of CD4 T lymphocytes then decreases significantly. The lymphoid organs no longer compensate for this destruction. Opportunistic infections make their appearance, defining the AIDS stage.

Much progress has been made in the fight against the HIV pandemic. Antiretroviral treatment (ART) is based on the use of three molecules (triple therapy) interacting with HIV on its different targets. ART aims to achieve and maintain undetectable plasma viral load. It must restore immunity, measurable by measuring the level of CD4. Finally, it significantly reduces the risk of transmission in patients controlling viral replication [5].

TAR blocks viral multiplication by acting on the replicative cycle stages of HIV by interference. Currently there are six classes of antiretrovirals for five targets located in the replicative cycle:

• Three enzymatic targets: nucleos(t)idic and non-nucleos(t)idic reverse transcriptase inhibitors (NRTIs and NNRTIs), protease inhibitors (PIs), and integrase inhibitors (IINs);

The new 2015 WHO guidelines stipulate that anyone infected with HIV should be systemati-

Human Immunodeficiency Virus-Hepatitis B Virus (HIV-HBV) Coinfection

http://dx.doi.org/10.5772/intechopen.78567

73

The global epidemics of hepatitis B and HIV have led to a new understanding of the complex interactions between these two viruses. Due to similar patterns of contamination (bloodstream, sexual pathway, and mother-to-child transmission), the high prevalence of HBV infection among the 33 million people living with HIV (PLHIV) across the world is about 10% [6]. In highly endemic areas such as the sub-Saharan Africa, this prevalence can be as high as

According to the WHO, nearly 240 million people are chronically infected with HBV worldwide. Of these, 4 million are coinfected with HIV. Overall, coinfection rates range from 5 to

cally put on ART, regardless of CD4 T-cell level or viral load.

**Non-nucleosidic inhibitors of reverse transcriptase (NNIRT)**

Efavirenz(EFV) Etravirine (ETR) Névirapine (NVP) Rilpivirine (RPV) **Protease inhibitor (PI)** Atazanavir/r (ATV/r) Darunavir/r (DRV/r) Fosamprenavir/r (FPV/r) Indinavir/r (IDV/r) Lopinavir/r (LPV/r) Nelfinavir (NFV) Saquinavir/r (SQV/r) Tipranavir/r (TPV/r) **Integrase inhibitors** Dolutégravir (DTG) Elvitégravir (EVG) Raltégravir (RAL) **Fusion inhibitor**

Enfuvirtide (ENF ou T20)

**CCR5 antagonist** Maraviroc (MRC)

**2. General information on HIV-HBV coinfection**

15% and leads us systematically to seek HIV/HBV coinfection.




"opportunistic" infections. Eventually, the infected subject dies as a result of this generalized

The natural history of HIV infection has been divided into two major phases. The seroconversion stage occurs in the first 6 weeks after infection, a period between the time of infection and the appearance of antibodies. In some patients this phase is accompanied by an influenza state. During this phase, viral replication is intense (every day 1 billion viruses are produced), where viral load levels up to more than 1 million copies per mL of plasma [4], and the patient

Asymptomatic phase: This is the clinical latency phase. The immune system continuously destroys the viruses to keep the viral load low (no virological latency). At the same time the CD4 count will gradually decrease. This phase may persist for several years (up to

Symptomatic phase: It lasts from a few months to several years. The immune system begins to weaken and no longer effectively controls viral replication. The number of CD4 T lymphocytes then decreases significantly. The lymphoid organs no longer compensate for this destruction. Opportunistic infections make their appearance, defining the AIDS

Much progress has been made in the fight against the HIV pandemic. Antiretroviral treatment (ART) is based on the use of three molecules (triple therapy) interacting with HIV on its different targets. ART aims to achieve and maintain undetectable plasma viral load. It must restore immunity, measurable by measuring the level of CD4. Finally, it significantly reduces the risk

TAR blocks viral multiplication by acting on the replicative cycle stages of HIV by interference. Currently there are six classes of antiretrovirals for five targets located in the replicative cycle:

• Three enzymatic targets: nucleos(t)idic and non-nucleos(t)idic reverse transcriptase inhibitors (NRTIs and NNRTIs), protease inhibitors (PIs), and integrase inhibitors (IINs);

of transmission in patients controlling viral replication [5].

• One protein target: fusion inhibitor (IF); and

**Nucleoside inhibitors of reverse transcriptase (NIRT)**

• One cell target: antagonist of the CCR5 co-receptor.

is very infectious. CD4 T-cell level drops transient but usually returns to baseline.

immunosuppression (AIDS stage).

72 Advances in HIV and AIDS Control

The chronic phase has two stages.

15 years).

stage.

Abacavir (ABC) Stavudine (D4T) Ténofovir (TDF) Lamivudine (3TC) Didanosine (DDI) Zidovudine (AZT) Emtricitabine (FTC) The new 2015 WHO guidelines stipulate that anyone infected with HIV should be systematically put on ART, regardless of CD4 T-cell level or viral load.
