HIV Life Cycle

The life cycle is divided into many phases which starts with attachment to a cell as the first process of infection and ends with new virus budding out of the infected cell. Just as the influenza virus has an affinity for the cells of the respiratory tract (lungs) so HIV has an affinity for the immune system cells—especially the T helper cells (known as a CD4 T Cell).

Phase 1

The first phase is attachment when HIV comes into contact with an immune cell. When the protruding portions of HIV come in contact with the CD4+ cellular receptor of the cell various changes occur which allow the virus to fuse to the host cell (fusion), and the genetic material of the virus is able to enter the cell.

Phase 2

Once the virus has entered the cell the viral RNA (originally in its own capsid) is released into the cell followed closely by the making of double stranded DNA from single stranded RNA (third phase). The enzyme reverse transcriptase assists in this process.

The viral DNA is then integrated into the host DNA using another viral enzyme called integrase. Simply put, the viral DNA has now hijacked the host DNA and is able now to produce more virus RNA through a process called transcription. In this process RNA is produced in several forms as part of the process that will help produce viral proteins, and eventually form new viral particles. The protein building blocks are cleaved (joined) using another viral enzyme called protease, and migrate to the edge of the cell as viral proteins to form new viruses (virions).

Phase 3

The final phase is called budding. As the new virus moves out of the cell it takes with it part of the cell outer membrane as part of its own structure. Once outside the cell the virions mature to form new infectious viruses that may go on to infect more cells and repeat this process. Top

Disease Progression After Infection

Disease progression from infection to AIDS follows a set pattern in most infected individuals, although the rate of disease progression varies from one person to the other.

• Rapid progressors take 3–6 years
• Average progressors take 8 years
• Slow progressors take 15 years
• There is a small group of people who are classified as non-progressors. The slow progression of these individuals is thought to be as a result of genetically inherited factors.

HIV attacks cells in the immune system that have a certain type of receptor called CD4+. When an individual is first infected the initial stage of the disease is characterised by rapid spread of the virus throughout the body and an intensive phase of viral replication resulting in high quantities of virus and a corresponding decrease in CD4+ count.

As the body’s immune responses begin to take effect and antibodies are produced the amount of virus declines and the immune system recovers. The period between infection and the production of antibodies is known as the window period and it is during this interval of time that an infected person may test negative for HIV. It is also the reason why people who test negative should repeat the test after three months in case they had been recently infected.

The control of HIV by the immune system then continues over a period known as the ‘well phase’. During this time viral replication is contained, although there is a steady weakening of the immune system, indicated by a decrease in the CD4+ count by anywhere between 40–80 cells per year.

The rate of disease progression to AIDS is dependant on a variety of factors, one of which is the viral ‘set point’. This is the level of HIV in the blood established after initial infection. A person with a low viral set point—in other words a small amount of HIV in the blood—is less likely to develop advanced disease at a rapid rate; a person with a high viral set point—in other words a high level of virus in the blood—is likely to show more raid disease progression. Other factors that may influence the person’s progression to the advanced stages of HIV may include other factors such as nutrition, stress levels, and other lifestyle issues.

Once the CD4+ count falls below 350 then there is an increased likelihood that certain of the opportunistic infections associated with advanced disease manifest, and the types and numbers of infections may increase as the patient’s CD4+ count drops lower and below 200.

It is on this basis that the indicator for starting treatment has been established in many countries as a CD4+ count of 200 or less, or when certain opportunistic infections become evident—whichever is the earlier.

Once treatment is started then the whole process can be reversed and there is normally an increase in CD4+ count and a corresponding decrease in viral load. Top

Stages of HIV Infection

Infection with HIV causes a spectrum of clinical problems beginning at the time of sero-conversion (infection) and terminating with AIDS and death. It is now recognised that it may take between 7 and 10 years, and possibly longer, for AIDS to develop after sero-conversion.

The clinical stages of HIV infection are:

1. Acute infection
2. Asymptomatic disease/silent phase
3. Early symptomatic disease
4. AIDS

Stage 1: Acute Infection

Acute infection can occur by exposure to the bodily fluids of an infected person. Hence, any behaviour that increases one’s exposure to bodily fluids will increase risk of infection.

Specific behaviours include:

Sexual Transmission

• Largely heterosexual in developing countries.
• Male homosexuals account for a significant proportion in developed countries
• Rape

Parenteral Transmission

• Needle sharing amongst drug users (mostly in developed countries)
• Re-use of inadequately sterilized needles
• Transfusion of HIV infected blood or blood products
• Needlestick injury

Vertical Transmission

• The virus can be transmitted to the foetus during pregnancy or after birth via breastfeeding

Following infection there is a period of intense, unchecked viral replication occurring some two to four weeks after infection and lasting about one to two weeks, after which the patient recovers and is henceforth seropositive for HIV antibodies.

Though HIV replication is massive, most patients only experience mild flu-like symptoms at this stage. Typically the illness is sudden in onset and characterized by a fever, swelling of the lymph glands, a measles like rash over the whole body and ulcers in the mouth and sometimes on the genitalia.

Disease of the gastrointestinal tract is often involved, manifesting as anorexia, nausea, vomiting and diarrhoea. Patients may also present with inflammation of the pharynx and dysphasia, meningitis or encephalitis. This acute HIV syndrome does not occur in all individuals infected with the virus and many individuals who are HIV positive do not recall ever having experienced the illness. It has been estimated that approximately 50–70% of individuals who are HIV+ experience acute HIV illness. This syndrome is rarely seen in children.

Stage 2: Asymptomatic Disease

During this stage, an individual is not aware clinically of being infected, laboratory tests such as the antibody test are positive, but the presence of the virus is usually not as readily detectable as during the acute illness.

The duration of asymptomatic infection varies widely from individual to individual.

The median asymptomatic period is 10 years in gay or bisexual men. Some patients decline rapidly (i.e. 2 years) but 10–15% of patients may show no signs of progression for 10 or more years.

Intravenous drug users generally have a shorter asymptomatic period. Some patients may have no symptoms, even as CD4+ counts fall to extremely low levels, though this is rare. Other patients may intermittently experience malaise, lethargy, weakness and anorexia. As these symptoms are usually mild and resolve in time, patients do not consider them indications of serious disease and do not seek medical attention.

A patient’s lack of symptoms does not mean that the virus is dormant. HIV actively replicates during the asymptomatic period, primarily in the lymph nodes and lymphoid tissue. In fact, 90% of all HIV particles reside (and thrive) in the lymph nodes. The lymph nodes are particularly important because large numbers of CD4+ cells routinely migrate through them. During HIV infection, the lymph nodes trap free virus and infected CD4+ cells, thus creating a perfect environment for the infection of new CD4+ cells.

Sooner or later clinical signs and symptoms develop and the patient then advances to the next stage.

Stage 3: Early Symptomatic Disease

The immune system has become engaged in a constant battle with the rapidly replicating virus. Approximately 50 million to 2 billion new virus particles are created each day. The immune system responds by replenishing the peripheral blood with up to 2 billion new CD4+ cells per day.

The immune system can hold HIV in check for many years, but will eventually begin to lose the battle. The virus begins to destroy the CD4+ cell population. As CD4+ counts continue to drop, signs and symptoms more specific to HIV disease arise. These signs and symptoms are:

• Persistent generalised lymphodenopathy (PGL)
• Oral lesions (thrush, leukoplakia, ulcers)
• Shingles (painful rash affecting a defined area of skin)
• Thrombocytopenia (reduced platelet count)
• Early stages of neurological disease (aseptic meningitis/ peripheral neuropathy)

Stage 4: Acquired Immuno-Deficiency Syndrome

The diagnostic elements of this end-stage of HIV infection have undergone various changes under different classification systems over the years. The advent of AIDS marks an important milestone in the course of the infection. An irreversible step has been reached when the diagnosis of AIDS is made. Recovery from individual opportunistic infections may well occur and there may also be remission for tumours. However, they do recur, usually with increasing severity and frequency and become more and more difficult to treat until finally the patient dies, on an average after about 18 months to two years after the onset of AIDS.

Essentially the components of AIDS consist of the direct consequences of damage by HIV as well as the indirect consequences of immunosuppression.

The patient has developed AIDS if the following are present:

1. The patient is HIV positive
2. The CD4+ count is 200 cells per mm³ or less
3. There is an AIDS defining disease such as:
   • Kaposi’s sarcoma
   • Pneumocystis carinii pneumonia
   • Retinitis due to cytomegalovirus
   • Meningitis/encephalitis due to cryptococcal or toxoplasmosis infection
   • Pulmonary, miliary or extra-pulmonary tuberculosis
   • Dementia for no other reason (HIV encephalopathy)
   • Other cancers such as lymphoma also associated with AIDS. These may present with enlarged lymph nodes, liver and/or spleen.

Approximately 80% of patients with AIDS die of secondary infections caused by bacteria, protozoa, fungi or other viruses. Many of these microbes can appear in HIV-infected patients before the onset of AIDS. Many of these secondary infections can be treated at any stage of HIV disease but patients with AIDS are particularly at risk of severe complications of secondary infections. Patients with AIDS have a high risk of certain neoplastic diseases.

Prognosis

Time taken for progression is the conventional measure from infection to AIDS related disease manifestation.

Five years after exposure approximately 15% of patients will have progressed to AIDS, and of these, half will have died.

Of the remaining 85% less than one third will have constitutional symptoms of infection, less than two thirds will be completely asymptomatic and the remainder will only have lymphodenopathy.

Ten years after exposure, 50% will have progressed, of whom 80% will have died. Of the 50% who have not progressed to AIDS, one half will have constitutional symptoms, one third will have only lymphodenopathy and the rest will be asymptomatic with CD4+ counts ranging from >200 to 500.

Factors affecting progression of HIV to AIDS

Time taken for progression from HIV infection to AIDS may differ between individuals. This may be due in part to the presence of some of the following factors:

• Method of infection and the incubation period: may differ between those infected via blood and those infected via homosexual contact
• The number of virus particles transferred
• Simultaneous infection with other viruses or bacteria
• Infection with a strain of virus that is more virulent than others
• Specific biochemical abnormalities, such as deficiency of the peptide glutathione
• Age: In general, individuals over 30 years of age and young children develop AIDS faster than adolescents or young adults
• Genetic makeup
• Behaviour, such as drug abuse, which suppresses the immune system
• Use of anti-viral therapy (can delay progression to AIDS). Top

Risks and Modes of Transmission

Risks are associated mainly with sexual behaviour. HIV is transmitted through the exchange of body fluids, and thus is principally sexually transmitted since this is the main means of such exchange—almost 80% of transmission is through sexual exchange of body fluids.

Anal sex	Very high: The rectum is a fragile tissue prone to tears when penetration occurs
Dry sex	Very high: Involves removal of the natural lubrication or the vaginal tract, a preference amongst some males
Vaginal sex	High: With increased risk when the woman is during her menstrual cycle and also with the presence of sexually transmitted diseases
Kissing, deep throat, lip contact	Low–Medium: Risk may be increased with poor oral hygiene which includes the presence of bleeding gums and sores
Oral sex	Low–Medium: Risk may be increased with poor oral hygiene which includes the presence of bleeding gums and sores
Sex with a condom / femidom	Very low: Providing the condom is of good quality and is placed over the penis correctly or the femidom inserted into the vagina correctly
Intimate Touching	Nil–Low: Risk increases if finger penetration occurs and cuts occur at the base of the finger nails
Abstinence	Nil: No sexual practices equals no risk

The majority of people that are infected with HIV are likely to have acquired the infection sexually. HIV is present in the majority of body fluids some of which are infectious and some of which are not. The major body fluids are infectious but many people believe that any body fluid is infectious.

Infectious Body Fluids	Non Infectious Body Fluids
Blood, all body fluids containing blood	Tears
Vaginal secretions	Sweat
Semen	Saliva*
Pericardial fluid	Nasal secretions*
Peritoneal fluid	Vomit*
Pleural fluid	Faeces*
Cerebrospinal fluid	Urine*
Amniotic fluid

*If any of the above are mixed with blood they could be considered infectious

It should be noted that there are vast ranges of variability within the sexual routes of transmission. This is due to a variety of factors:

• The stage of the disease of the infected person (individuals in sero-conversion and at the advanced stages of the disease have higher viral loads and are therefore likely to be more infectious)
• The type of HIV
• The infecting persons sexual health (for example: the presence or absence of sexually transmitted diseases)
• The sexual health of the person who may become infected (presence or absence of sexually transmitted diseases)
• Age (Youngsters are at greater risk due to lifestyle and greater libido, desire for sex)
• New research shows that uncircumcised men are at greater risk

The second principle means of transmission is by means of mother to child transmission accounting for some 630,000 infections annually in Africa. In the USA, where treatment is readily available for individuals and mothers affected by HIV, the number of infections by this means in 2003–2004 was less than 200.

Other routes of transmission include:

• Intravenous drug use: Up to 10%
• Blood transfusions: 5% and
• Exposure to infection through needles etc.: 0.01%

Infection Route Sexual intercourse	Risk of Infection
Female-to-male transmission	1 in 700 to 1 in 3000
Male-to-female transmission	1 in 200 to 1 in 2000
Male-to-male transmission	1 in 10 to 1 in 1600
Oral Sex	6%-8% of transmission
Needles
Needle stick	1 in 200
Needle sharing	1 in 150
Transfusion of infected blood	95 in 100
Transmission from mother to infant
Without AZT treatment	1 in 3–5
With AZT treatment	Less than 1 in 10
Combination antiretroviral therapy	1 in 50

Top

The HIV Test

Testing: The basics

Many places provide private and confidential testing for HIV both within the public and the private sector which include for example:

Doctors rooms Hospitals Community health centres

Family planning clinics Sexually transmitted disease clinics Laboratories

Most of these places provide free or inexpensive HIV testing. It is important to get tested at a place that also has HIV and AIDS counselling. Counsellors are often able to answer questions and help the individual understand what the test results mean.

How the Test Works

The HIV test detects the body’s response to HIV infection by reacting with any antibodies that may have been produced in response to HIV infection. That means that the test does not detect the virus itself. Antibodies are special cells your body creates to fight an infection. After getting HIV, most people develop antibodies that can be seen within 3 months; the average time is 25 days after exposure to HIV. In rare cases, it can take up to 6 months to be able to see HIV antibodies. Because of this an individual should get tested 6 months after their most recent possible exposure to HIV. If an individual has a test that is negative then it should be repeated 3 months later in case the person is in the ‘window period’: the period during which the body may be producing antibodies to HIV.

types of test

Rapid tests are becoming increasingly popular in Africa as they are highly reliable (over 99% accuracy), cost effective, and give the result within a short period of time—ormally within half an hour. The patient may also be able to see the kit and the result. Either a small sample of blood (from a prick on the finger) or sample of mucus from the inside of the cheek or gums is taken, depending on the test. Should the test be positive then a confirmatory test would normally done either using a different rapid test or a sample of blood may be taken to carry out an ELISA (enzyme linked immunoassay) test.

The ELISA test was the standard used by many clinics before the advent of the rapid test. The patient’s blood is sent to a laboratory in a plain tube. Two separate specimens are tested using two different kits to confirm patient identity. The test result however is not immediate and results may take several days before the patient is given the results. This often places stress on the patient. In the event of the result being positive a confirmatory test is done as with the rapid test above.

The Western Plot is used less in current testing environments. The test is labour intensive and can take longer than any of the other tests. It was frequently used as a confirmatory test if the patient had tested positive using the ELISA test.

T-cell, CD4+ counts

There are two main types of T-cells that play an important role in the immune system. The CD4+ T-cell has CD4+ molecules on its surface and is responsible for gearing up the body’s immune system to respond to microorganisms such as viruses. The CD8 T-cell has CD8 molecules on its surface and is responsible for destroying cells that are infected with organisms such as viruses. CD8 T-cells also produce anti-viral substances.

HIV is able to attach itself to the CD4+ cell allowing the virus to enter and infect these cells. The virus multiplies in the infected cell, producing many copies of the virus and destroying the CD4+ cell in the process. The body produces billions of new CD4+ cells to replace those that have been destroyed.

CD4+ cells are measured by the number of cells per cubic millimetre (mm) of blood. This is referred to as the CD4+ count. A normal count is between 600–1200 CD4+ cells per mm³ of blood but this may vary from person to person and may even vary from day to day and hour to hour. Younger persons may have higher counts than older people. A further measurement is the percentage of CD4+ cells of the total, white immune cell population. In HIV negative individuals this is normally around 40% but in HIV positive individuals can be lower. If the CD4+ percentage falls below 15% then there is serious risk of opportunistic infection.

When a person is infected with HIV, the CD4+ count falls over a period of time, even though it may remain stable for a period. As a rough guide the CD4+ count will drop by 60–80 cells/mm³ every year during the early stages of infection. It is important to monitor the CD4+ count on a regular basis as this will help the healthcare provider determine when to start drug therapy and to give treatments to prevent opportunistic infections. If a patient is already on therapy it is also used to measure the effectiveness of treatment.

The decision to start therapy should always be made in consultation with a doctor. There are various guidelines worldwide as to when to start therapy. However, a consistent CD4+ count below 350 is considered low, and should be monitored on a regular basis. At levels of 200–250 an individual is at serious risk of opportunistic infection and a doctor may also recommend that antibiotics are taken to prevent PCP (a form of pneumonia). Therapy should definitely be initiated at any CD4+ count below 200.

Once therapy is started the CD4+ count may start to rise, which could reflect an improvement in immune function and the body's ability to fight infection. Once the CD4+ count rises above 350 and is maintained above this level an individual may not need to take additional treatments (over and above the antiretroviral therapy) to prevent opportunistic infections.

Regular monitoring of CD4+ count and viral load (see below) helps determine whether the treatment is working. As long as the trend is upward or stable then there is positive indication of the effectiveness of the treatment. A consistent fall in CD4+ count may indicate that the treatment is becoming less effective but any decision to change treatment will normally be taken in conjunction with a viral load test. One therapy has started it is normally recommended that CD4+ counts be done every 6 months together with a viral load test.

Viral Load

A viral load test counts the number of HIV particles in a sample of blood. The result is expressed as the number of ‘copies’ of HIV RNA per ml (millilitre) of blood. It is now generally accepted that 10,000 copies per ml or less is considered low and 50,000 copies per ml and above is considered high.

There are several tests that measure the amount of HIV although the tests become unreliable at low levels of infection. Originally this limit was less than 400 or 500 copies per ml. New ‘ultra-sensitive’ tests are now able to measure to a lower limit of 50 copies per ml and these may be the tests that are more widely used. Depending on the test used, a measurement below the limit of detection may be referred to as ‘undetectable’.

The test for viral load is one of the monitoring tests that can indicate disease progression and may give an indication as to the likely course of HIV infection if left untreated. It is generally accepted that higher viral load may lead to more rapid disease progression but other indicators such as CD4+ count and symptoms should also be considered when deciding to take treatment.

When treatment is started, the viral load test gives an indication of how effective the anti-HIV regimen is. When starting a treatment, or switching from one treatment to another, an individual should have a baseline viral load test prior to the start or change of drug treatment. A second test should follow a couple of months later so as to monitor the effect of the drugs. It is then normal to have repeat tests every six months or more frequently if there are indications that the regimen is not effective.

In some people a drug combination can reduce the viral load to 'undetectable', even if the CD4+ count remains low. An ‘undetectable’ viral load normally means that the virus is less likely to develop resistance to the drugs and that viral replication is very slow. It is normal practice to try and reduce the viral load to ‘undetectable’ at the 50- copy level by the 24th week of treatment.

If an individual is taking the drugs correctly and viral load starts to rise again it may mean that the drugs are becoming less effective, most probably due to viral resistance. It should be noted that the viral load only gives an indication of the amount of HIV in the blood and does not measure virus present in the brain and genital fluids where the effect of drugs may vary. The individual may therefore still be infectious to others.

TREATMENT: THE CHOICES

HIV/AIDS remains an incurable condition. Only antiretroviral drugs have been clinically proven to extend life and make the condition manageable. Antiretroviral drugs should not be considered a stand-alone solution and lifestyle adjustments even with the drugs involve good nutrition, exercise and the maintenance of safe sexual practices.

In the last few years, drug prices have fallen dramatically and drugs are widely available in many countries either free or as part of access programmes. Although it is a matter of individual choice for an individual to decide to take advantage of the treatment options currently available, the individual MUST commit to being adherent to the defined treatment programme to qualify for an AllLife product (as defined in the AllLife Adherence and Monitoring Protocol - this includes an obligation to initiate and remain on antiretroviral therapy if a CD4+ count of less than 200 cells/mm³ is registered).

What Is Combination Therapy?

Combination therapy is the term used for using three or more drugs to treat HIV. Some drugs have already been combined into one pill to make dosing easier (e.g. Combivir®). It is also called triple therapy or HAART.

Do The Drugs Really Work?

In every country that uses HAART, AIDS-related deaths and illnesses have dropped dramatically. Treatments work for women, men and children, and they work however you were infected—whether sexually, through IV (intravenous) drug use, or by blood transfusion. Taking drugs exactly as prescribed will reduce the amount of virus in the body to tiny amounts. Regular monitoring using blood tests checking for CD4+ count and viral load is required to check that the drugs are still working. This is the only reason why AllLife is able to offer life insurance to people living with HIV.

How Long Will The Drugs Work?

An individual taking the drugs in the prescribed manner could use the same combination to remain healthy for years. If the drugs are not taken correctly, drug failure will develop and the individual will have to start another (often stronger) combination.

What About Side Effects?

Many people worry about treatments because of the side effects:

• Most side effects are usually mild
• They can often be managed easily
• The risk of serious side effects is very small
• Most people find that treatments become an ordinary part of their daily life

Are The Drugs A Cure?

The current drugs are a treatment but not a cure. They stop the progression of HIV and let the immune system start to repair itself, but the individual still remains HIV positive. Even people who have been on combination therapy successfully for several years still have small amounts of HIV in their bodies. This is often dormant in cells. Top

Antiretroviral Drugs

The Beginnings

Once upon a time there was a failed anti-cancer drug called zidovudine, which had been rejected because it had unpleasant side effects. Twenty years later, under the name AZT, it became the vanguard of medicines in the fight against HIV.

AZT was seen as a breakthrough: the first medication that seemed to attack the virus itself. It was thus the first real hope for people infected with HIV, which until then had almost certainly led to death.

In 1986 a clinical trial on patients in eight American cities was stopped after four months because AZT seemed to have such dramatic effects on the virus. The next year AZT (Retrovir) became available commercially as the first antiretroviral to be registered by the US Food and Drug Administration (FDA).

Unfortunately, follow-up research was not so optimistic. Clinical trials in Europe found no long-term benefit from using AZT, especially if patients started taking the drug before they showed signs of AIDS. And, worryingly, healthy patients taking AZT seemed to die faster than their sicker counterparts.

What was not appreciated then was that taking only one antiretroviral at a time—monotherapy—has only a short-term benefit, because the virus mutates so rapidly that drug-resistant strains swiftly become dominant.

Until 1991 AZT was the only—and very expensive—hope available for people sick with AIDS. In that year another antiretroviral, ddI (didanosine, Videx), created specifically for patients who had become resistant to AZT, was registered. By this time the World Health Organisation estimated that 10 million people were infected with HIV worldwide, of whom a million were in the United States.

In 1992 ddC (zalcitabine, Hivid), was approved for use in the US, followed by d4T (Zerit) in 1994 and 3TC (Epivir, lamivudine) in 1995.

All these drugs are classified as nucleoside reverse transcriptase inhibitors (NRTIs or “nukes”), which resemble the chemical building blocks—nucleosides—used by reverse transcriptase, a key enzyme required by HIV for intracellular replication. NRTIs have a chemical twist, which ensures that, once taken up by the enzyme, the NRTI molecules terminate the building of the viral DNA chain, stalling virus production.

The problem is that HIV can show cross-resistance to different drugs in the same group. So, for example, a patient treated with AZT monotherapy is likely to quickly show some resistance to other NRTIs, but, because they are all slightly different, dual therapy using two drugs in the same class is still more effective and sustainable than monotherapy. This was demonstrated in 1997 when the FDA registered Combivir, a combination drug containing both AZT and 3TC. In this case resistance to one drug appeared to counter resistance to the other.

1996 brought registration of nevirapine (Viramune, NVP), the first in a new class of antiretrovirals: non-nucleoside transcriptase inhibitors (NNRTI), a group of drugs that stops the duplication of viral DNA by directly disabling the reverse transcriptase enzyme itself.
The development of NNRTIs was a breakthrough because they worked against viruses that had become resistant to NRTIs, and researchers quickly found that dual therapy - using two drugs simultaneously - was most effective when the drugs were from two different groups. Other NNRTIs, such as delarvirdine (Rescriptor, DLV) and efavirenz (Sustiva, EFV) followed in 1997 and 1998.

NNRTIs were overshadowed by the arrival of a third class of drugs—protease inhibitors (PIs). These work at a later stage of the HIV life cycle by interfering with the protease enzyme, the other key enzyme required by HIV for intracellular replication. First off the blocks with FDA registration were saquinavir (Fortovase, SQV, Invirase) in 1995, followed by ritonavir (Norvir, RTV) and indinavir (Crixivan, IDV) in 1996, nelfinavir (Viracept, NFV) in 1997 and amprenavir (Agenerase, APV) in 1999.

With three groups of anti-HIV drugs available, HAART began to evolve, and antiretrovirals became known as Lazarus drugs because they appeared to resurrect patients from near death.

The latest class of antiretrovirals to be developed are fusion inhibitors, which prevent HIV from infecting human cells by blocking the viral proteins used to dock into cell membranes. To date there is only one FDA-registered fusion inhibitor—enfuvirtide (Fuzeon, T-20), registered in March 2003. Fuzeon has to be administered by injection, is expensive and has many side effects but, because it is the first of a totally different class of drugs, it offers another chance to patients who have become resistant to other treatment regimes.

Types of Antiretroviral Drugs

Internationally there are some 19 drugs available to fight HIV—some of them in combination pills. The number of generic versions available in Africa continue to grow whilst drug companies are starting to work together to bring many existing drugs onto the market as combination pills.

Drugs are divided into three classes and may have two to three different names:

• A generic name: The name of the drug whether it is made by one drug company or another
• An abbreviated name
• A brand name: The name specific to that particular company.

We can understand this by reference to chocolate. Chocolate is a generic name for a type of food, Nestle or Cadbury are brand names. On the container the drug is normally identified by the brand name since this is what the drug companies want us to remember. The generic name will normally appear elsewhere. For example Zerit is a brand name and elsewhere Stavudine will be used. This can be difficult for patients who may receive different brands of the same drugs from month to month because of availability problems. It is therefore important that the patient realises that whatever brand they are given, the drugs are basically the same and offer the same standards of purity and efficacy.

There are currently four groups of drugs used to fight HIV:

• Nucleoside reverse transcriptase inhibitors (also known as NRTIs or Nukes)
• Non-Nucleoside reverse transcriptase inhibitors (also known as NNRTIs or non-Nukes)
• Protease inhibitors (also known as Proteases or PIs)
• Entry fusion inhibitors (also known as Fusion Inhibitors or EIs)

The last group is not yet available in Africa but the other three groups are commonly used to fight HIV.

The targets of the drugs are the three enzymes used by HIV in the multiplication process. These enzymes are:

• Reverse transcriptase
• Integrase (not yet targeted by currently available drugs)
• Protease

The nukes and non-nukes target reverse transcriptase (in different ways) and protease is targeted by the proteases. By interfering with the lifecycle of HIV it means that viral replication is unable to continue and new viral particles are not produced.

Currently available drugs in Africa are listed below (brand names have been omitted as different brands may be available in different countries). Not all drugs will be available throughout Africa—common ones are highlighted with an asterisk (*):

Nukes

Generic Name	Abbreviation
Emtricitabine (on expanded access programme from Gilead)	FTC
Lamivudine*	3TC
Zalcitabine	ddC
Zidovudine*	AZT or ZDV
Didanosine*	ddI
Didanosine: delayed-release	ddI
Tenofovir DF (on expanded access programme from Gilead)	TDF
Stavudine*	d4T
Stavudine: delayed-release	d4T
Abacavir*	ABC

Non-Nukes

Generic Name	Abbreviation
Delavirdine	DLV
Efavirenz*	EFV
Nevirapine*	NVP

Proteases

Generic Name	Abbreviation
Amprenavir	APV
Indinavir*	IDV
Nevirapine*	NVP
Saquinavir* (soft gel cap)	SQV (SGC)
Saquinavir* (hard gel cap)	SQV (HGC)
Lopinavir/ritonovir*	LPV/r
Fosamprenavir	FPV
Ritonovir*	RTV

Africa still has a limited number of drugs available mainly due to the fact that many of the new drugs have not been approved for local use. The existing numbers of drugs however represent a powerful arsenal of tools to use to fight HIV. Top

Modern myths associated with HIV

Myths arise from lack of accurate information about many elements in life. For example people use to think that the world was flat. Now we know that is not true. Below are some of the modern myths associated with HIV—and the truth..

Myth: I can get HIV from touching a person affected or being in the same room as them.

This is not true. Touching or hugging someone with HIV does not mean you will be infected with the virus. The virus is principally transmitted sexually through sexual intercourse and exchange of body fluids. People also think that by sharing cups, knives and forks etc they can also be infected. This is also not true.

Myth: People with HIV all look the same.

This is not true. How can we tell if someone has HIV by just looking at them? Some people think that people with the virus look thin but people come in all shapes and sizes anyway. The only way to tell whether someone has the virus is through an HIV test.

Myth: If I am tested HIV positive then I have AIDS.

This is not true. AIDS is a certain stage of the disease. People with HIV can live healthy and productive lives for many years before they develop advanced disease (AIDS). HIV and AIDS are lumped together (often wrongly) which gives the impression that they are one and the same.

Myth: If I have sex with someone outside my relationship I will not get HIV.

This is not true. Being unfaithful has its risks. We always say that when you have sex outside a relationship it becomes like a ‘lottery’ – your chances of winning are always there just as are your chances of catching HIV. Unless you know the status of your sexual partners and their sexual behaviour you must always take precautions.

Myth: If I have sex with another HIV positive person then I will automatically be infected.

This is not true. When we have unprotected sex with an HIV positive person you may or may not be infected by them. However why take the risk? Top

Myth: If I use a condom then people will think I am HIV positive.

This is not true. The modern approach is to use a condom to protect yourself from infections you may get from your partner. You may not know their status or their sexual history so there is nothing wrong with saying ‘lets condomise to protect each other—until we know our status’.

Myth: People who have HIV are being punished by God.

A disease is not a punishment; it is a fact of life. There are many diseases that we get such as polio, smallpox, measles, and flu. HIV is just another viral disease that, because it is sexually transmitted, is considered a punishment by some people. People who are infected have been made to feel guilty by those who are not infected. If you were infected by your partner (who does have many partners) how can you be at fault? Other people say that it was introduced to punish homosexuals. This is also not true.

Myth: Culture says that using a condom is wrong.

Cultures are created by groups of people making decisions for others. If a group of elders make a decision then it often becomes culture and entrenched in local community law. The fact is that culture is often based on lack of information and therefore culture has to be changed just as laws are.

Myth: HIV will never affect me.

HIV affects everybody. There are certain cultural and economic groupings that think they can never be exposed to the virus. This is often incorrect and based on the assumption that they are better than others. This applies to communities where there are high levels of sexual taboo and an atmosphere of self-righteousness. Some of the biggest increases in HIV infection are being seen in these groups.

Myth: I cannot get HIV because I am not a homosexual or a prostitute.

This is not true. Anybody who is sexually active can be exposed to HIV and be infected if they have more than one partner.

Myth: I can be cured if I have sex with a virgin or a child, as I will then be purified.

This is not true. Once the person is infected with HIV it cannot be removed from the infected person’s body since there is still no cure. Sleeping with a virgin or a child is often an act of desperation based on wrong information. Forcing someone to have sex with you is also illegal. Top

Myth: People with HIV cannot continue to work.

This is not true. People with HIV can continue to lead productive lives for many years. It is important to accept them as part of the workforce and not stigmatise their condition. Very often people with HIV get depressed because of the reaction of others. This can be a problem as they often feel unwanted.

Myth: Children should not be allowed to go to school because they are HIV positive.

This is not true. Children who are HIV positive should not be treated any differently to those who are HIV negative. Their status is not a danger to anyone else and they are entitled to live normal lives. This is part of stigma to the disease.

Myth: My religion says I must not use a condom because it stops pregnancy.

Many religions suggest that stopping pregnancy is not right. It is important to recognize that whether you have sex or not is your decision and some churches promote abstinence. However HIV has nothing to do with pregnancy and the use of condoms in this instance is to prevent transmission. Many Churches however would disagree with this stance.

Myth: Women are the source of HIV as there are more women infected than men.

Men are more infectious than women. The reason more women are infected is that they are more prone to infection because of their biological make up and the fact that during sex, men insert their penises into women and their semen (if infected) may come into direct contact with the woman’s vaginal fluids (especially blood) and lead to the mixing of body fluids. The man, however, is protected by his own skin.

Myth: HIV is transmitted by the sperm and means an infected man can produce an HIV positive baby.

This is not correct. HIV is found in the body fluids—the fluids which contain the sperm. When a baby is conceived it is HIV negative in the womb, and is normally infected at birth when the mother goes into labour and the baby’s body fluids and the mother’s blood mix. If the mother has a sexually transmitted disease during pregnancy then there is a risk that due to certain factors that the baby may be infected in the womb. Top

Myth: I have heard that people who are tested and are HIV positive become HIV negative and are cured.

This is not correct. People who are tested positive will always be positive. Sometimes people who test positive are diagnosed as such because the test is faulty. It is therefore important to confirm a positive result with a second test. Once people produce antibodies to the virus (the test detects these antibodies—not the virus) the body will always have the antibodies. Just the same occurs with other infections such as chicken pox. There is however one exception—babies born to HIV positive mothers often test HIV positive. This is because the antibodies pass from the mother to the child during pregnancy. If the child is not infected with HIV then these antibodies will disappear after 15–18 months. However if the baby is infected during birth or during the period while the mother is breastfeeding the infant then the child will develop it’s own antibodies to HIV.

Myth: The antiretroviral drugs will kill me.

This is not true. Taking the drugs at the correct stage of the disease will help to fight HIV infection. It sometimes happens that people are diagnosed at the late stages and it is the infections that kill them even after they have started taking the drugs.

Myth: The antiretroviral drugs do not work.

This is not true. The drugs are very effective if taken correctly. People fail on treatment because often they do not take drugs correctly and the virus learns to fight the drugs. This is called resistance.

Myth: Immune boosters will stop me from dying.

This is not correct. Immune boosters often contain a mixture of vitamins and minerals that help to keep the immune system healthy but eventually the HIV will destroy the immune system. Very often immune boosters are expensive and the money can be better spent on good healthy foods such as fruit and vegetables that are good sources of vitamins, minerals and antioxidants, AND they fill your stomach. When an individual starts treatment it is important that they inform their doctors of what other herbs and supplements they are taking since many of these products interfere with the antiretroviral drugs and may impact on the success of treatment. Top