HIV

• Human immunodeficiency virus (HIV) is a single stranded RNA retrovirus that infects and replicates within the human immune system using host CD4 cells

  Without treatment, destruction of the immune system can lead to acquired immune deficiency syndrome (AIDS)
• Epidemiology:

  • HIV-1 = most common, found worldwide, if untreated leads to AIDS
  • HIV-2 = distribution restricted to west Africa
• CD4 receptors:

  • T helper cells
  • Macrophages
  • Dendritic cells
  • Langerhans' cells
  • CD4 count useful predictor for opportunistic infections and malignancy
• Pathogenesis:

  • Enters host cell by binding gp120 to CD4 receptor and co-receptors (CCR5)
  • Releases RNA and enzymes into the host cell
  • Key enzymes = reverse transcriptase, intergrase and protease
  • RNA is reverse transcribed into DNA
  • DNA integrated into host cell genome
  • HIV takes over host cell transcription and translation mechanism - allow replication of virus
  • Once new HIV virions formed they are released from the cell by budding
• Stages of HIV infection:

  • Stage 1 - primary HIV infection (seroconversion)
  • Stage 2 - chronic HIV infection (asymptomatic infection/clinical latency)
  • Stage 3 - AIDS
• Primary infection (seroconversion):

  • Develops within 2-4 weeks after exposure
  • HIV binds to CD4+ receptor found on the surface of T helper lymphocytes, monocytes, macrophages and dendritic cells
  • Infected CD4+ cell dies and releases large number of new virions
  • High level of viral replication, making the person highly infectious
  • CD4+ levels fall in response to the initial rapid replication of HIV
  • Can cause mild-to-moderate non specific symptoms = seroconversion illness
• Chronic HIV (asymptomatic/clinical latency):

  • Immune response controls the virus, limiting symptoms despite a persistent low level of viral replication
  • Are still infectious
  • This stage can continue for 10-15 years with symptoms only presenting when the hosts ability to replenish CD4+ stops
• AIDS:

  • When the persistent HIV infection compromises the ability of the immune system to replenish CD4+ cells
  • The CD4+ cell count drops bellow 200 cells
  • Ability of the immune system to combat infection is severely compromised - opportunistic infection and malignancy
  • Multiple AIDS defining illnesses
• Transmission:

  • Via infected bodily fluids
  • Most commonly through vaginal, oral and anal sexual intercourse
  • Vertical transmission from mother to child - pregnancy, childbirth or breastfeeding
  • Inoculation - needle sharing, blood products and occupational exposure
• Demographic groups high risk of HIV:

  • Men who have sex with men
  • Female sexual contacts of MSM
  • From an area with a high prevalence of HIV - Africa
  • In current or former relationship with HIV positive individual
• Lifestyle and social risk factors include:

  • Intravenous drug use
  • Occupational exposure (such as accidental needlestick injury)
  • Sexual risk factors such as unprotected anal or vaginal sex with one or multiple partners, and having another sexually transmitted infection such as hepatitis B or hepatitis C
• Clinical features of primary HIV infection from most common to least:

  • Fever
  • Malaise
  • Arthralgia
  • Lymphadenopathy
  • Loss of appetite
  • Maculopapular rash
  • Myalgia
  • Pharyngitis
  • Oral ulcer
  • Weight loss
• Asymptomatic disease:

  • After seroconversion - CD4 count increases, but still abnormal
  • Viral load stabilizes
  • May have persistent generalized lymphadenopathy
  • For most there is a steady decline in CD4 over 6-8 years
  • For some there is a more rapid decline over 6-12 months
• As the common symptoms are non-specific, UK national guidelines for HIV testing recommend HIV testing should be administered to patients presenting with glandular fever-like symptoms, fever of unknown origin, lymphadenopathy and unexplained weight loss, unexplained neutropenia, anaemia and thrombocytopenia.
• Clinical features of longstanding HIV infection:

  • Constitutional - fever/night sweats, weight loss, lymphadenopathy
  • Haematology - unexplained pancytopenia
  • Respiratory - Infection with pneumocystis jirovecii, TB, bacterial pneumonia
  • Neurological - confusion, seizures, focal symptoms
  • Oral - candidiasis, aphthous ulcers, abscess
  • GI - oesophageal candidiasis, diarrhoea
  • Derm - fungal skin and nail infection, shingles, warts
  • GU - candidiasis, HSV, warts
• AIDS can be defined as the development of one or more AIDS-defining illnesses in the presence of HIV infection or by a CD4+ count <200 cells/µL. 
• Examples of AIDS defining illnesses:

  • Pneumocystis pneumonia
  • Kaposi's sarcoma - soft tissue malignancy
  • Cryptococcal meningitis (fungal)
  • Cerebral toxoplasmosis - parasitic infection
  • CMV retinitis
  • Non-Hodgkin's lymphoma
  • Oesophageal candidiasis
  • TB
  • Primary CNS system lymphoma
• Routine HIV testing recommended for those at increased risk of exposure:

  • MSM
  • Female sexual contacts of MSM
  • Black Africans
  • People reporting current or prior injecting drug use
  • Sex workers
  • Prisoners
  • Trans women
  • People from a country with high diagnosed seroprevalence (>1%)
  • People reporting sexual contact with anyone from a country with high diagnosed seroprevalence regardless of where contact occurs
  • Individuals known to have/have had a mother living with HIV and who do not have documented HIV-negative status
• 2 methods for HIV testing:

  • Lab-based testing (via venepuncture)
  • Self-sampling, self-testing and rapid point of care tests (finger prick, mouth swab)
  • Window period from exposure and accurate detection of infection varies from 45-90 days
  • Fourth-generation tests are the first line - ELISAs that detect the presence of HIV IgM and IgG antibodies and the viral p24 antigen
  • Need repeat sample to confirm positive result
  • Point of care testing uses 3rd generation tests - results can be ready in under an hour
• In a newly diagnosed patient:

  • Confirm the diagnosis
  • Assess degree of immunosuppression
  • Identify co-existing conditions
  • Identify drug resistance
• Management:

  • Anti-retroviral therapy (ART)
  • Improved prognosis and life expectancy
  • Combination tablets available - improved quality of life and pill burden
• If left untreated, AIDS will cause death within around 20 months
• Antiretroviral therapy:

  • HIV is highly mutagenic and can quickly develop drug resistance
  • 2 nucleoside reverse transcriptase inhibitors (NRTIs) (tenofovir disoproxil and emtricitabine), combined with one of:
  • Integrase inhibitor
  • Non-nucleoside reverse transcriptase inhibitor (NNRTI)
  • Boosted protease inhibitor
• Potential adverse effects of ART:

  • Hypersensitivity
  • Mood/behaviour/sleep changes
  • Hyperlipidaemia
  • Lipodystrophy
  • Renal impairment
  • Hepatic toxicity
  • Peripheral neuropathy
  • Bone marrow suppression
  • Pancreatitis
• Pre-exposure prophylaxis (PrEP)

  • Adults at high risk of HIV
  • Combination of emtricitabine and tenofovir disoproxil (NRTIs)
  • Taken daily
  • Men or transgender people who have sex with men
  • HIV negative sexual partners of HIV positive individuals with a detectable or unknown viral load
• Post-exposure prophylaxis (PEP)

  • Needs to be initiated within 72 hours of exposure
  • Emtricitabine, tenofovir disoproxil and raltegravir (integrase inhibitor)
  • Continued for 28 days
  • Not recommended for human bites or needle stick injuries unless the donor is known to be highly viral or high risk
•  a HIV-positive individual with sustained undetectable levels of HIV in their blood cannot transmit the virus to their sexual partners.
• For HIV-positive individuals, their progress should be monitored every 3-6 months for early disease and every 2-3 months in late disease. This should include assessment for opportunistic infection, viral load (PCR test for HIV RNA) and CD4+ count.
• The virus is suppressed within 3-6 months of ART initiation
• Pneumocystis carinii is the most common life-threatening opportunistic infection in HIV positive individuals
• Life expectancy for those living with HIV is lower than the general population but has lengthened over time as the effectiveness and tolerability of ART has improved.
• HIV antibodies usually appear 4-6 weeks after infection but can take up to 12 weeks:

  • If test negative and exposed within the past 3 months retest in 4 weeks