September 04, 2016

HIV Disease - An Overview of Causes, Symptoms, Treatment and Key Facts

The Human immunodeficiency virus (HIV) is a blood-borne virus typically transmitted via sexual intercourse, shared intravenous drug paraphernalia, and mother-to-child transmission (MTCT), which can occur during the birth process or during breastfeeding. HIV disease is caused by infection with HIV-1 or HIV-2, which are retroviruses in the Retroviridae family, Lentivirus genus.

HIV targets the immune system and weakens people's defence systems against infections and some types of cancer. As the virus destroys and impairs the function of immune cells, infected individuals gradually become immunodeficient. Immune function is typically measured by CD4+ T cell count (also known as CD4 count). Immunodeficiency results in increased susceptibility to a wide range of infections and diseases that people with healthy immune systems can fight off.

The most advanced stage of HIV infection is Acquired Immunodeficiency Syndrome (AIDS), which can take from 2 to 15 years to develop depending on the individual. AIDS is defined by the development of certain cancers, infections, or other severe clinical manifestations.

The HIV virus
The HIV virus

Signs and symptoms

The symptoms of HIV vary depending on the stage of infection. Though people living with HIV tend to be most infectious in the first few months, many are unaware of their status until later stages. The first few weeks after initial infection, individuals may experience no symptoms or an influenza-like illness including fever, headache, rash or sore throat.

As the infection progressively weakens the immune system, an individual can develop other signs and symptoms, such as swollen lymph nodes, weight loss, fever, diarrhoea and cough. Without treatment, they could also develop severe illnesses such as tuberculosis, cryptococcal meningitis, and cancers such as lymphomas and Kaposi's sarcoma, among others.

Transmission

HIV can be transmitted via the exchange of a variety of body fluids from infected individuals, such as blood, breast milk, semen and vaginal secretions. Individuals cannot become infected through ordinary day-to-day contact such as kissing, hugging, shaking hands, or sharing personal objects, food or water.

Risk factors

Behaviours and conditions that put individuals at greater risk of contracting HIV include:
  • having unprotected anal or vaginal sex;
  • having another sexually transmitted infection such as syphilis, herpes, chlamydia, gonorrhoea, and bacterial vaginosis;
  • sharing contaminated needles, syringes and other injecting equipment and drug solutions when injecting drugs;
  • receiving unsafe injections, blood transfusions, medical procedures that involve unsterile cutting or piercing; and
  • experiencing accidental needle stick injuries, including among health workers.

Diagnosis

Serological tests, such as rapid diagnostic tests (RDTs) or enzyme immunoassays (EIAs), detect the presence or absence of antibodies to HIV-1/2 and/or HIV p24 antigen. When such tests are used within a testing strategy according to a validated testing algorithm, HIV infection can be detected with great accuracy. It is important to note that serological tests detect antibodies produced by an individual as part of their immune system to fight off foreign pathogens, rather than direct detection of HIV itself.

Most individuals develop antibodies to HIV-1/2 within 28 days and therefore antibodies may not be detectable early after infection, the so-called window period. This early period of infection represents the time of greatest infectivity; however HIV transmission can occur during all stages of the infection.

It is best practice to also retest all people initially diagnosed as HIV-positive before they enrol in care and/or treatment to rule out any potential testing or reporting error.

HIV testing services

HIV testing should be voluntary and the right to decline testing should be recognized. Mandatory or coerced testing by a health-care provider, authority or by a partner or family member is not acceptable as it undermines good public health practice and infringes on human rights.

Some countries have introduced, or are considering, self-testing as an additional option. HIV self-testing is a process whereby a person who wants to know his or her HIV status collects a specimen, performs a test and interprets the test results in private. HIV self-testing does not provide a definitive diagnosis; instead, it is an initial test which requires further testing by a health worker using a national validated testing algorithm.

All HIV testing services must include the 5 C’s recommended by WHO: informed Consent, Confidentiality, Counselling, Correct test results and Connection (linkage to care, treatment and other services).

Classifications

Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease, and the CDC classification system for HIV infection. The CDC's classification system is more frequently adopted in developed countries. Since the WHO's staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.

The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007. The WHO system uses the following categories:
  • Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.
  • Stage I: HIV infection is asymptomatic with a CD4 count greater than 500 per microlitre (µl or cubic mm) of blood. May include generalized lymph node enlargement.
  • Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl.
  • Stage III: Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung, and a CD4 count of less than 350/µl.
  • Stage IV or AIDS: severe symptoms which include toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma. A CD4 count of less than 200/µl.
The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008 and 2014. This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in five groups. In those greater than six years of age it is:
  • Stage 0: the time between a negative or indeterminate HIV test followed less than 180 days by a positive test
  • Stage 1: CD4 count ≥ 500 cells/µl and no AIDS defining conditions
  • Stage 2: CD4 count 200 to 500 cells/µl and no AIDS defining conditions
  • Stage 3: CD4 count ≤ 200 cells/µl or AIDS defining conditions
  • Unknown: if insufficient information is available to make any of the above classifications
For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.

Prevention

Individuals can reduce the risk of HIV infection by limiting exposure to risk factors. Key approaches for HIV prevention, which are often used in combination, include:

1. Male and female condom use

Correct and consistent use of male and female condoms during vaginal or anal penetration can protect against the spread of sexually transmitted infections, including HIV. Evidence shows that male latex condoms have an 85% or greater protective effect against HIV and other sexually transmitted infections (STIs).

2. Testing and counselling for HIV and STIs

Testing for HIV and other STIs is strongly advised for all people exposed to any of the risk factors. This way people learn of their own infection status and access necessary prevention and treatment services without delay. WHO also recommends offering testing for partners or couples.

Tuberculosis (TB) is the most common presenting illness among people with HIV. It is fatal if undetected or untreated and is the leading cause of death among people with HIV- responsible for 1 of every 3 HIV-associated deaths. Early detection of TB and prompt linkage to TB treatment and antiretroviral therapy (ART) can prevent these deaths. It is strongly advised that HIV testing services integrate screening for TB and that all individuals diagnosed with HIV and active TB urgently use ART.

3. Voluntary medical male circumcision

Medical male circumcision, when safely provided by well-trained health professionals, reduces the risk of heterosexually acquired HIV infection in men by approximately 60%. This is a key intervention in generalized epidemic settings with high HIV prevalence and low male circumcision rates.

4. Antiretroviral (ART) use for prevention

4.1 ART as prevention

A 2011 trial has confirmed if an HIV-positive person adheres to an effective ART regimen, the risk of transmitting the virus to their uninfected sexual partner can be reduced by 96%. The WHO recommendation to initiate ART in all people living with HIV will contribute significantly to reducing HIV transmission.

4.2 Pre-exposure prophylaxis (PrEP) for HIV-negative partner

Oral PrEP of HIV is the daily use of antiretroviral (ARV) drugs by HIV-uninfected people to block the acquisition of HIV. More than 10 randomized controlled studies have demonstrated the effectiveness of PrEP in reducing HIV transmission among a range of populations including serodiscordant heterosexual couples (where one partner is infected and the other is not), men who have sex with men, transgender women, high-risk heterosexual couples, and people who inject drugs.

In September 2015, WHO published the “Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV”, that recommends PrEP as a prevention choice for people at substantial risk of HIV infection as part of combination prevention approaches.

4.3 Post-exposure prophylaxis for HIV (PEP)

Post-exposure prophylaxis (PEP) is the use of ARV drugs within 72 hours of exposure to HIV in order to prevent infection. PEP includes counselling, first aid care, HIV testing, and administering of a 28-day course of ARV drugs with follow-up care.

Updated WHO guidelines issued in December 2014 recommend PEP use for both occupational and non-occupational exposures and for adults and children. The new recommendations provide simpler regimens using ARVs already being used in treatment. The implementation of the new guidelines will enable easier prescribing, better adherence and increased completion rates of PEP to prevent HIV in people who have been accidentally exposed to HIV such as health workers or through unprotected sexual exposures or sexual assault.

5. Harm reduction for injecting drug users

People who inject drugs can take precautions against becoming infected with HIV by using sterile injecting equipment, including needles and syringes, for each injection. A comprehensive package of interventions for HIV prevention and treatment includes:
  • needle and syringe programmes;
  • opioid substitution therapy for people dependent on opioids and other evidence based drug dependence treatment;
  • HIV testing and counselling;
  • HIV treatment and care;
  • access to condoms; and
  • management of STIs, tuberculosis and viral hepatitis.

6. Elimination of mother-to-child transmission of HIV (EMTCT)

The transmission of HIV from an HIV-positive mother to her child during pregnancy, labour, delivery or breastfeeding is called vertical or mother-to-child transmission (MTCT). In the absence of any interventions during these stages, rates of HIV transmission from mother-to-child can be between 15-45%. MTCT can be nearly fully prevented if both the mother and the child are provided with ARV drugs throughout the stages when infection could occur.

WHO recommends options for prevention of MTCT (PMTCT), which includes providing ARVs to mothers and infants during pregnancy, labour and the post-natal period, and offering life-long treatment to HIV-positive pregnant women regardless of their CD4 count.

In 2015, 77% (69–86%) of the estimated 1.4 (1.3-1.6) million pregnant women living with HIV globally received effective antiretroviral drugs to avoid transmission to their children.

Treatment

HIV can be suppressed by combination ART consisting of 3 or more ARV drugs. ART does not cure HIV infection but controls viral replication within a person's body and allows an individual's immune system to strengthen and regain the capacity to fight off infections.

In 2015, WHO released a new "Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV.” The guidelines recommend that anyone infected with HIV should begin antiretroviral treatment as soon after diagnosis as possible.

By end-2015, 17.0 million people living with HIV were receiving ART globally which meant a global coverage of 46% (43–50%).

Based on WHO’s new recommendations, to treat all people living with HIV and offer antiretrovirals as an additional prevention choice for people at "substantial" risk, the number of people eligible for antiretroviral treatment increases from 28 million to all 36.7 million people. Expanding access to treatment is at the heart of a new set of targets for 2020 which aim to end the AIDS epidemic by 2030.

Key Facts

  • HIV continues to be a major global public health issue, having claimed more than 35 million lives so far. In 2015, 1.1 (940 000–1.3 million) million people died from HIV-related causes globally.
  • There were approximately 36.7 (34.0–39.8) million people living with HIV at the end of 2015 with 2.1 (1.8–2.4) million people becoming newly infected with HIV in 2015 globally.
  • Sub-Saharan Africa is the most affected region, with 25.6 (23.1–28.5) million people living with HIV in 2015. Also sub-Saharan Africa accounts for two-thirds of the global total of new HIV infections.
  • HIV infection is often diagnosed through rapid diagnostic tests (RDTs), which detect the presence or absence of HIV antibodies. Most often these tests provide same day test results; essential for same day diagnosis and early treatment and care.
  • There is no cure for HIV infection. However, effective antiretroviral (ARV) drugs can control the virus and help prevent transmission so that people with HIV, and those at substantial risk, can enjoy healthy and productive lives.
  • It is estimated that currently only 54% of people with HIV know their status. In 2014, approximately 150 million children and adults in 129 low- and middle-income countries received HIV testing services.
  • By end-2015, 17.0 million people living with HIV were receiving antiretroviral therapy (ART) globally.
  • Between 2000 and 2015, new HIV infections have fallen by 35%, AIDS-related deaths have fallen by 28% with some 7.8 million lives saved as a result of international efforts that led the global achievement of the HIV targets of the Millennium Development Goals.
  • Expanding ART to all people living with HIV and expanding prevention choices can help avert 21 million AIDS-related deaths and 28 million new infections by 2030.

WHO response

The Sixty-ninth World Health Assembly endorsed a new "Global Health Sector Strategy on HIV for 2016-2021". The strategy includes 5 strategic directions that guide priority actions by countries and by WHO over the next six years.

The strategic directions are:
  • Information for focused action (know your epidemic and response).
  • Interventions for impact (covering the range of services needed)
  • Delivering for equity (covering the populations in need of services).
  • Financing for sustainability (covering the costs of services).
  • Innovation for acceleration (looking towards the future).
  • WHO is a cosponsor of the Joint United Nations Programme on AIDS (UNAIDS). Within UNAIDS, WHO leads activities on HIV treatment and care, HIV and tuberculosis co-infection, and jointly coordinates with UNICEF the work on the elimination of mother-to-child transmission of HIV.
Also read: HIV-prevention drug Truvada approved by FDA

Reference(s)
1). World Health Organization: HIV/AIDS - WHO Fact Sheets. Accessed 4 September 2016. Available here: http://www.who.int/mediacentre/factsheets/fs360/en/
2). Centers for Disease Control: HIV/AIDS. Accessed 31 August 2016. Available here: http://www.cdc.gov/hiv/basics/whatishiv.html
3). Wikipedia, the free encyclopedia: HIV/AIDS. Accessed 3 September 2016. Available here: https://en.wikipedia.org/wiki/HIV/AIDS

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