HIV

• Acquired immunodeficiency syndrome (AIDS)


  First recognized in 1981, caused by the human immunodeficiency virus (HIV-1)

  
• HIV-2


  Causes a similar illness to HIV-1 but is less aggressive and restricted mainly to western Africa

  
• Simian immunodeficiency viruses (SIVs)


  Closely related African primate viruses from which HIV-1 and HIV-2 originated

  
• Sequence analysis has led to the estimate that HIV-1 was introduced into humans in the early 1930s

  
• SIV


  Weak virus suppressed by human immunity within weeks of infection, several transmissions from human to human in quick succession necessary to allow enough time to mutate into HIV

  
• Since 1981 AIDS has grown to be the second leading cause of disease burden world-wide and the leading cause of death in Africa, where it accounts for over 20% of deaths
• Highly active retroviral therapy (HAART)


  With three or more drugs, has improved life expectancy to near normal in the majority of patients receiving it, with an 80% reduction of mortality since its introduction
• Immune deficiency


  A consequence of continuous high-level HIV replication leading to virus and immune-mediated destruction of the key immune effector cell, the CD4 lymphocyte

  
• In 2012, the World Health Organization (WHO) estimated that there were 35.3 million people living with HIV/AIDS, 2.5 million new infections and 2.1 million deaths

  
• The cumulative death toll since the epidemic began is over 36 million (2012) in 2013 1.4 million death, the vast majority of cases occurring in sub-Saharan Africa where over 11.4 million children are now orphaned
• No cure, no vaccine
• Modes of transmission of HIV


  Sexual (man to man, heterosexual and oral), Parenteral (blood or blood product recipients, injection drug-users and those experiencing occupational injury), Vertical (pregnancy, delivery, breast feeding)

  
• World-wide, the major route of transmission (> 75%) is heterosexual
• About 5-10% of new HIV infections are in children and more than 90% of these are infected during pregnancy, birth or breastfeeding

  
• Transmission risk after exposure


  Over 90% for blood or blood products, 15-40% for the vertical route, 0.5-1.0% for injection drug use, 0.2-0.5% for genital mucous membrane spread and under 0.1% for non-genital mucous membrane spread
• After >25 years of scrutiny,📌 there is no evidence that HIV is transmitted by casual contact or that the virus can be spread by insects, such as by a mosquito bite

  
• There have been approximately 100 definite and 200 possible cases of HIV acquired occupationally in health-care workers
• Such infections are substantially more frequent in developing nations, where it is estimated that 40% of syringes/needles used in injections are reused without sterilisation
• HIV


  A single-stranded RNA retrovirus from the Lentivirus family
• Infection establishment


  1. After mucosal exposure, HIV is transported to the lymph nodes via dendritic, CD4 or Langerhans cells, where infection becomes established

  2. Free or cell-associated virus is then disseminated widely through the blood with seeding of 'sanctuary' sites (e.g. central nervous system) and latent CD4 cell reservoirs

  3. With time, there is gradual attrition of the CD4 cell population, resulting in increasing impairment of cell-mediated immunity and susceptibility to opportunistic infections
• Primary infection


  Symptomatic in 70-80% of cases and usually occurs 2-6 weeks after exposure
• Clinical features of primary infection


  • Fever with rash
  • Pharyngitis with cervical lymphadenopathy
  • Myalgia/arthralgia
  • Headache
  • Mucosal ulceration
• Asymptomatic infection


  Follows primary infection and lasts for a variable period, during which the infected individual remains well with no evidence of disease except for the possible presence of persistent generalised lymphadenopathy (PGL, defined as enlarged glands at ≥ 2 extra-inguinal sites)
• Mildly symptomatic disease (ARC)


  Develops in the majority, indicating some impairment of the cellular immune system, corresponding to AIDS-related complex (ARC) conditions but by definition are not AIDS-defining, with a median interval from infection to the development of symptoms of around 7-10 years
• HIV symptomatic diseases


  • Oral hairy leucoplakia
  • Recurrent oropharyngeal candidiasis
  • Recurrent vaginal candidiasis
  • Severe pelvic inflammatory disease
  • Bacillary angiomatosis
  • Cervical dysplasia
  • Idiopathic thrombocytopenic purpura
  • Weight loss
  • Chronic diarrhoea
  • Herpes zoster
  • Peripheral neuropathy
  • Low-grade fever/night sweats
• Acquired immunodeficiency syndrome (AIDS)


  Defined by the development of specified opportunistic infections, tumours etc.
• AIDS-defining diseases


  • Oesophageal candidiasis
  • Cryptococcal meningitis
  • Chronic cryptosporidial diarrhoea
  • CMV retinitis or colitis
  • Chronic mucocutaneous herpes simplex
  • Disseminated Mycobacterium avium intracellulare
  • Pulmonary or extrapulmonary tuberculosis
  • Pneumocystis carinii pneumonia
  • Progressive multifocal leucoencephalopathy
  • Recurrent non-typhi Salmonella septicemia
  • Cerebral toxoplasmosis
  • Extrapulmonary coccidioidomycosis
  • Invasive cervical cancer
  • Extrapulmonary histoplasmosis
  • Kaposi's sarcoma
  • Non-Hodgkin lymphoma
  • Primary cerebral lymphoma
  • HIV-associated wasting
  • HIV-associated dementia
• Diagnosis of HIV infection


  1. demonstration of antibodies to HIV and/or B- the direct detection of HIV or one of its components

  
• Antibodies to HIV


  Generally appear in the circulation 2–12 weeks following infection

  
• ELISA (EIA)


  The standard blood screening test for HIV infection, an extremely good screening test with a sensitivity of >99.5%

  
• Western blot


  The most commonly used confirmatory test, demonstrating antibodies to products of all three of the major antigenes of HIV (env, pol &gag) is conclusive evidence of infection with HIV

  
• p24 antigen capture assay


  The simplest of the direct detection tests, has its greatest use as a screening test for HIV infection in patients suspected of having the acute HIV syndrome, as high levels of p24 antigen are present prior to the development of antibodies

  
• Acute HIV infection


  HIV RNA is always detectable, and the HIV p24 antigen is often positive, with an abrupt onset of clinical symptoms

  
• Recent infection


  The period after acute HIV when anti-HIV antibodies are developing out to 6 months after HIV acquisition

  
• HIV RNA detection tests


  Reverse transcriptase PCR, branched DNA, and nucleic acid sequence–based amplification, used for diagnosis, establishing initial prognosis, determining the need for therapy, and monitoring the effects of therapy

  
• CD4+ T cell counts


  The reduction in the number of CD4 cells circulating in peripheral blood is tightly correlated with the amount of plasma viral load, both monitored closely in patients and used as measures of disease progression
• Patients with CD4+ T cell counts <200 are at high risk of disease from P. jiroveci while patients with CD4+ T cell counts <50 are at high risk of disease from CMV, mycobacteria of M.avium complex &/0r T.gondi
• Patients with HIV infection should have CD4+ T cell measurements performed at the time of diagnosis and every 3–6 months thereafter, with more frequent measurements if a declining trend is noted

  
• Treatment


  Slows the course and leads to near normal life expectancy, reduces the risk of death and complications
• Without treatment, average survival time from infection is 9-11 years