A Distance Learning Course of the Directorate of Learning Systems (AMREF)

Unit 5: Antiretroviral Therapy in Adults and Adolescents

A distance learning course of the Directorate of Learning Systems (AMREF)

© 2007 African Medical Research Foundation (AMREF)

This course is distributed under the Creative Common Attribution-Share Alike 3.0 license. Any part of this unit including the illustrations may be copied, reproduced or adapted to meet the needs of local health workers, for teaching purposes, provided proper citation is accorded AMREF. If you alter, transform, or build upon this work, you may distribute the resulting work only under the same, similar or a compatible license. AMREF would be grateful to learn how you are using this course and welcomes constructive comments and suggestions. Please address any correspondence to:

The African Medical and Research Foundation (AMREF)

Directorate of Learning Systems

P O Box 27691 – 00506, Nairobi, Kenya

Tel: +254 (20) 6993000

Fax: +254 (20) 609518

Email:

Website:

Writer: Dr Patrick Odawo

Editor: Charles Omondi

Cover design: Bruce Kynes

Technical Co-ordinator:Joan Mutero

The African Medical Research Foundation (AMREF wishes to acknowledge the contributions of the Commonwealth of Learning (COL) and the Allan and Nesta Ferguson Trust whose financial assistance made the development of this course possible.

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CONTENTS

INTRODUCTION

UNIT OBJECTIVES

SECTION 1: HISTORY AND EPIDEMIOLOGY OF HIV/AIDS

Introduction

Section 1: Objectives

1.1 What is the Origin of HIV?

1.2 Epidemiology of HIV/AIDS

1.3 Transmission of HIV

1.4 Factors Influencing HIV Transmission

1.5 What is the Impact of HIV/AIDS?

SECTION 2: BIOLOGY OF THE HIV VIRUS

Introduction

Section Objectives

2.1 Structure of The HIV Virus

2.2 Life Cycle of The HIV Virus

2.3 Sites of Action of Antiretroviral Drugs

2.4 Types of HIV Viruses

SECTION 3: PATHOGENESIS AND NATURAL PROGRESSION OF HIV INFECTION IN ADULTS AND ADOLESCENTS

Introduction

Section Objectives

3.1 The Human Immune System

3.2 Natural Progression of HIV Disease

3.3 HIV Disease Staging

Abbreviations

AIDSAcquired Immune Deficiency Virus

ART Antiretroviral therapy

ARV Antiretroviral

AZT Zidovudine

CBCComplete Blood Count

C&SCulture & sensitivity

DAARTDirectly Administered ART Therapy

DNAdeoxyribonucleic acid

DTCDiagnostic Testing and Counselling

ELISA Enzyme-linked imunosorbent Assay )

FDCFollicular Dendritic Cells

HAART Highly active antiretroviral therapy

HIVHuman Immunodeficiency Virus

HTLV-IIIHuman T-lymphotrophic virus III

IECInformation Education and Communication

KDHSKenya Demographic and Health Survey

LAVLymphadenopathy associated virus

MTCTMother to Child Transmission

NASCOPNational AIDS/STD Control Program

OIsOpportunistic Infections

PEPPost-exposure Prophylaxis

PCP Pneumocystis carinii pneumonia

PLWHAPeople Living With HIV/AIDS

RNA Ribonucleic acid

SIVSimian Immunodeficiency Virus

SSASub Saharan Africa

STIsSexually Transmitted Illnesses

VCTVoluntary Counselling and Testing

WBWestern Blot

WHOWorld Health Organisation

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Introduction

Welcome to the first Unit in our course on “IntegratedHIV/AIDS Prevention, Treatment and Care”. Since the early 1980s when HIV was diagnosed, it remains a serious and threatening health crisis in the world. According to the World Health Organization, it is the 4th biggest killer worldwide.

In this unit we shall trace the origin of the HIVvirus, examine its structure, and how it affects our immune system.

This unit is divided into 4 sections. In the first section we shall address the history origin of this virus while in the second section we shall look at the biology of HIV in order to understand its structure and types. In the third and fourth section we shall discuss the progression of HIV infection and examine the World Health Organisation’s (WHO) clinical staging of HIV infection in adults.

This is an introductory unit which forms the basis for many of the topics that will follow in this course. You will therefore be called upon to review it from time to time as you go through this course. I believe you will enjoy working through this Unit.

Let’s start by looking at the objectives of this Unit.

Unit Objectives

By the end of this unit you should be able to:

• Discuss the history of HIV/AIDS;
• Describe the current status of HIV globally, regionally and nationally;
• Describe vulnerability factors in the spread of HIV;
• Discuss the impact of HIV/AIDS in the community;
• Describe the structure and life-cycle HIV as well as its types and sub-types;
• Identify the modes of HIV/AIDS transmission;
• Explain the effects of HIV on the immune system;
• Describe the progression of HIV infection;
• Discuss the WHO clinical staging of HIV infection in adults.

SECTION 1: HISTORY AND EPIDEMIOLOGY OF HIV/AIDS

Introduction

Let’s begin this section by quoting Dr Samuel Broder:

“In June of 1981 we saw a young gay man with the most devastating

immune deficiency we had ever seen. We said, ’We don’t know what this is,but we hope we don’t ever see another case like it again’.” (WHO, 1994, Words of Dr. Samuel Broder, then of the National Cancer Institute in the United States of America).

Welcome to the first section of this unit. In this section we are going to look at some of the theories that have been advanced in an attempt to explain the origin of HIV. Next we will discuss the epidemiology HIV and AIDS at the global, sub-Saharan and Kenyan levels. Finally we shall look at the transmission of HIV and factors that influence this transmission.

Section 1: Objectives

By the end of this section you should be able to:

• Outline at least 3 theories that attempt to explain the origin of HIV
• Describe the epidemiology if HIV at global sub-Saharan and country level
• Explain the modes of transmission of HIV
• Describe factors that influence the transmission of HIV

In the early 80s, specifically around 1981, doctors discovered a strange disease that was affecting gay men in the United States. The doctors noticed thatnumber of gay men in New York and San Franciscohad suddenly began to develop rare opportunistic infections and cancers that seemed stubbornly resistant to any treatment. It quickly became obvious that all the men were suffering from a common syndrome.

In 1983, scientists described the cause of the syndrome as a retrovirus that was variously referred to as Lymphadenopathy associated virus (LAV), AIDS associated retrovirus (ARV) and human T-lymphotrophic virus III (HTLV-III). In 1986, the Human Immunodeficiency Virus (HIV) was accepted as the international designation for the retrovirus in a WHO Consultative Meeting.

In Kenya, the first case of AIDS was described in Kenya in 1984 in Nairobi.

1.1 What is the Origin of HIV?

Well, am sure you have heard many theories about the origin of HIV. Before you read on, do the following activity.

List down at least three theories you have heard about the origin of HIV.
1.______
2.______
3.______
______

The origin of HIV remains a constant debate amongst health care workers and scientists. No one group has ever reached a consensus on the origin of HIV. However, several theories have been advanced to try to explain its origin.

It is now widely accepted that the Human Immunodeficiency Virus (HIV) bears close resemblance to the Simian Immunodeficiency Virus (SIV) which affects monkeys.It has been known for a long time that certain viruses can pass between species of animals. As animals ourselves, we are just as susceptible. When a viral transfer between animals and humans takes place, it is known as zoonosis.

Below are some of the most common theories about how this 'zoonosis' took place, and how SIV became HIV in humans:

The Hunter Theory: It is the most commonly accepted theory. It is said that the Simian Immunodeficiency Virus (SIV) was transferred to humans bychimpanzees. As you know in some parts of Africa Chimpanzees are hunted and eaten as food. So this theory believes that as a result of the hunting and handling of chimpanzees carcasses, their blood got into the cuts or wounds on the hunter. Normally the hunter's body would have fought off SIV, but on a few occasions it adapted itself within its new human host and become HIV-1. This theory is supported by the fact that there were several different early strains of HIV, each with a slightly different genetic make-up (the most common of which was HIV-1 group M). It is believed that every time SIV passed from a chimpanzee to a man, it developed in a slightly different way within his body, and thus produced a slightly different strain.On a few occasions, SIV adapted itself within its new humanhost and become HIV.

The Oral Polio Vaccine Theory:This theory states that the virus was transmitted via various medical experiments (iatrogenically) especially through the polio vaccines. This was especially thought to be through the oral polio vaccine called Chat was given to millions of people in the Belgian Congo, Ruanda and Urundi in the late 1950s. In order for the vaccine to be reproduced, it needed to be cultivated in living tissue. It is believed that the vaccine was cultivated on kidney cells taken from chimpanzees which were infected with SIV. Thus the polio vaccine became contamination with SIV and later affected large number of people who developed HIV. However, this theory was rejected when the scientists who developed the CHAT vaccine proved that the only kidney cells used were from the macaque monkey kidney cells which are do not get infected with SIV. Another reason why this theory was rejected was that HIV existed in humans long before the vaccine trials were carried out.

The Contaminated Needle Theory: According to this theory, African healthcare professionals were using one single syringe to inject multiple patients without any sterilization in between. This could have led to the rapid transfer of infection from one individual to another resulting in mutation from SIV to HIV. This theory is an extension of the hunter theory.

The Colonialism Theory: The colonial rule in Africa was particularly harsh and the locals were forced into labor camps where sanitation was poor and food was scare. SIV could easily have infiltrated the labor force and taken advantage of their weakened immune systems. Laborers were being inoculated with unsterile needles against diseases such as smallpox to keep them alive and working. Also, many of the camps actively employed prostitutes to keep the workers happy. All these factors may have led to the transmission and development of AIDS as a disease.

The Conspiracy Theory:Some people believe that HIV was manufactured in a laboratory or that it is man-made. Indeed, a survey conducted in the United States of America among African Americans, found that they believe the virus was manufactured as part of a biological warfare programme, designed to wipe them out in large numbers. While there is no evidence to disprove this theory, it can has however not been accepted because there were no genetic engineering technology at that time of emergence of AIDS.

Now let’s look at the epidemiology of HIV/AIDS.

1.2 Epidemiology of HIV/AIDS

The HIV pandemic has continued to evolve, in both magnitude and diversity. So what is the current status of the HIV epidemic? Well, as you well know, the vast majority of new infections occur in developing countries. This epidemic has taken its toll in Africa where it impact negatively on its social and economic life. Let us review its impact globally, in sub-saharan Africa and in Kenya.

Global Picture

HIV/AIDS is currently one of the biggest killer in the world. The Global AIDS Report from UNAIDS estimated thatthere were between 33.4 to 46.0 million people living with HIV globally in 2005. An estimated 4.1 million became newly infected with HIV and an estimated 2.8 million lost their lives to AIDS. About 1/3 of people living with HIV and AIDS are between 15 and 24 years of age.

Figure1: Figure of global HIV/AIDS distribution. Source: UNAIDS

Sub-Saharan Africa

As you can see from Figure 1, The HIV/AIDS burden resides in Africa, particularly Sub-Saharan Africa. Sub-Saharan Africa hosts a little more than one-tenth of the world’s population yet it is home to almost 64% of all people living with HIV (21.6 million–27.4 million]. Two million of them are children younger than 15 years of age. The 2005 statistics paint the following bleak picture:

-nine in ten children (younger than 15 years) living with HIV are found in sub- Saharan Africa.

-between 2.3 million–3.1 million people in the region became newly infected in 2005;

-2.0 million [1.7 million–2.3 million] adults and children died of AIDS.

-There were 12.0 million orphans living in sub-Saharan Africa in 2005.

-Three-quarters of all women (15 years and older) living with HIV are found in sub-Saharan Africa.

-Women comprise an estimated 13.2 million or 59%—of adults living with HIV in Africa south of the Sahara.

Southern Africa remains the global epicenter of the epidemic. Almost one in three people infected with HIV globally live in this subregion. Also about 43% of all children (under 15 years) and approximately 52% of all women (15 years and older) living with HIV in Sub-saharan Africa living with HIV are found in southern Africa. Compared to the rest of the African countries, national HIV infection levels in Southern Africaare exceptionally high and show no signs of abating.

Figure 1.2 below gives a comparison of the trends of HIV prevalence in different parts of Africa, demonstrating the increasing levels in Southern Africa.

Figure 1.2: Trends in HIV Prevalence in different parts of Africa

Kenya

The National AIDS/STD Control Program (NASCOP) estimates that by end of 2002, the national prevalence of HIV was 9.2% representing a reduction from the previous year when it was 13.4%. The Kenya Demographic and Health Survey (KDHS) of 2003 in a population survey found the prevalence rate to be 6.7%. The epidemic in Kenya, however, remains heterogeneous in its distribution with lower rates generally observed in rural communities than in urban centres. This range varies from 2-31%. Figure 1.3 below presents the distribution of HIV prevalence by age groups. The HIV prevalence in 2003 varied from 16.4% in 15 - 25 year olds to 27.9% in the age group over 45 years old. See figure 1.3 for distribution of HIV prevalence in Kenya.

Figure1.3: Distribution of HIV prevalence by age groups (NASCOP, 2005)

HIV and Women

HIV/AIDS has been described to depict a woman’s face. Over 50% of PLHA worldwide are women, whereas in Africa, 58% of people living with HIV/AIDSare women (see Figure 1.4).

Figure1.4: Gender distribution of HIV/AIDS (UNAIDS, 2006)

So we have just seen the magnitude of HIV and AIDS globally, in sub-Saharan Africa and nationally. Let’s now turn to how HIV is transmitted.

1.3 Transmission of HIV

I am sure you already have a good idea about how HIV is transmitted. Before you read on, take a few minutes to do the following activity.

List the primary modes of HIV transmission
______
______
______
______

Well done! I believe your list contained the following modes of transmission.

HIV is transmitted primarily through exposure to HIV infected blood or exchange of HIV containing bodily fluids. The 3 primary modes of transmission are:

Blood-to-blood transmission. This is through:

• Transfusion of HIV-infected blood or direct contact withthe blood;
• Exposure to HIV-contaminated needles, syringes, and other equipment;
• Donated organs;
• Traditional procedures involving scarification;

Sexual contact:

• unprotected vaginal, oral, or anal intercourse;
• direct contact with HIV-infected body fluids such as semen and cervical and vaginal secretions.

Perinatal transmission:

• Mother to child transmission of HIV during pregnancy, labor and delivery
• Mother to child transmission of HIV during breast-feeding

Figure 1.5: How HIV is spread

/ HIV CANNOT be transmitted by:

• Coughing or sneezing
• Being bitten by an insect
• Touching or hugging
• Kissing
• Going to a public bath/pool
• Using a public toilet
• Shaking hands
• Working or going to school with a person who is HIV infected
• Using telephones
• Drinking water or preparing or eating food
• Sharing cups, glasses, plates, or other utensils

Sexual contact is the most common route of HIV transmission. This includes heterosexual contact and homosexual contact (that is men having sex with men or MSM in short).

In resource-poor countries such as Kenya, heterosexual transmission is the primary mode of acquiring and is primarily responsible for the fact that HIV infection is increasing at a faster rate among women than among men in most parts of the world. In the developed countries such as the United States, men having sex with men (MSM) is the primary mode of HIV sexual transmission.

Mother to Child Transmission (MTCT) accounts for most cases of HIV infection in children worldwide. Children can also become infected with HIV through the same mode as those by which adults are infected (exposure to contaminated blood or other body fluids, eg, through transfusions of infected blood products, through contact with needles or other instruments contaminated with infected blood or other body fluids, and through sexual abuse).

The table below shows the contributions of the different modes of transmission towards HIV infection: