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Classification HIV is a member of the genus Lentivirus part of the family of Retroviridae Lentiviruses have many common morphologies and biological properties Many species are infected by lentiviruses which are characteristically responsible for long duration illnesses with a long incubation period Lentiviruses are transmitted as single stranded positive sense enveloped RNA viruses Upon entry of the target cell the viral RNA genome is converted to double stranded DNA by a virally encoded reverse transcriptase that is present in the virus particle This viral DNA is then integrated into the cellular DNA by a virally encoded integrase along with host cellular co factors so that the genome can be transcribed After the virus has infected the cell two pathways are possible either the virus becomes latent and the infected cell continues to function or the virus becomes active and replicates and a large number of virus particles that can then infect other cells are liberated There are two species of HIV known to exist HIV 1 and HIV 2 HIV 1 is the virus that was initially discovered and termed LAV It is more virulent more infective and is the cause of the majority of HIV infections globally The lower infectivity of HIV 2 compared to HIV 1 implies that fewer of those exposed to HIV 2 will be infected per exposure Because of its relatively poor capacity for transmission HIV 2 is largely confined to West Africa Comparison of HIV species Species Virulence Infectivity Prevalence Inferred origin HIV 1 High High Global Common Chimpanzee HIV 2 Lower Low West Africa Sooty Mangabey Signs and symptoms A generalized graph of the relationship between HIV copies viral load and CD4 counts over the average course of untreated HIV infection any particular individual s disease course may vary considerably CD4 T cell count cells per L HIV RNA copies per mL of plasma Infection with HIV 1 is associated with a progressive decrease of the CD4 T cell count and an increase in viral load The stage of infection can be determined by measuring the patient s CD4 T cell count and the level of HIV in the blood HIV infection has basically four stages incubation period acute infection latency stage and AIDS The initial incubation period upon infection is asymptomatic and usually lasts between two and four weeks The second stage acute infection lasts an average of 28 days and can include symptoms such as fever lymphadenopathy swollen lymph nodes pharyngitis sore throat rash myalgia muscle pain malaise and mouth and esophageal sores The latency stage which occurs third shows few or no symptoms and can last anywhere from two weeks to twenty years and beyond AIDS the fourth and final stage of HIV infection shows as symptoms of various opportunistic infections A study of French hospital patients found that approximately 0 5 of HIV 1 infected individuals retain high levels of CD4 T cells and a low or clinically undetectable viral load without anti retroviral treatment These individuals are classified as HIV controllers or long term nonprogressors Acute HIV infection Main article Acute HIV infection Main symptoms of acute HIV infection The initial infection with HIV generally occurs after transfer of body fluids from an infected person to an uninfected one The first stage of infection the primary or acute infection is a period of rapid viral replication that immediately follows the individual s exposure to HIV leading to an abundance of virus in the peripheral blood with levels of HIV commonly approaching several million viruses per mL This response is accompanied by a marked drop in the numbers of circulating CD4 T cells This acute viremia is associated in virtually all patients with the activation of CD8 T cells which kill HIV infected cells and subsequently with antibody production or seroconversion The CD8 T cell response is thought to be important in controlling virus levels which peak and then decline as the CD4 T cell counts rebound to around 800 cells per L the normal blood value is 1200 cells per L A good CD8 T cell response has been linked to slower disease progression and a better prognosis though it does not eliminate the virus During this period usually 24 weeks post exposure most individuals 80 to 90 develop an influenza or mononucleosis like illness called acute HIV infection the most common symptoms of which may include fever lymphadenopathy pharyngitis rash myalgia malaise mouth and esophagal sores and may also include but less commonly headache nausea and vomiting enlarged liver spleen weight loss thrush and neurological symptoms Infected individuals may experience all some or none of these symptoms The duration of symptoms varies averaging 28 days and usually lasting at least a week Because of the nonspecific nature of these symptoms they are often not recognized as signs of HIV infection Even if patients go to their doctors or a hospital they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms As a consequence these primary symptoms are not used to diagnose HIV infection as they do not develop in all cases and because many are caused by other more common diseases However recognizing the syndrome can be important because the patient is much more infectious during this period Latency stage A strong immune defense reduces the number of viral particles in the blood stream marking the start of the infection s clinical latency stage Clinical latency can vary between two weeks and 20 years During this early phase of infection HIV is active within lymphoid organs where large amounts of virus become trapped in the follicular dendritic cells FDC network The surrounding tissues that are rich in CD4 T cells may also become infected and viral particles accumulate both in infected cells and as free virus Individuals who are in this phase are still infectious During this time CD4 CD45RO T cells carry most of the proviral load AIDS Main article AIDS For more details on this topic see AIDS Diagnosis AIDS Symptoms and WHO Disease Staging System for HIV Infection and Disease When CD4 T cell numbers decline below a critical level of 200 cells per L cell mediated immunity is lost and infections with a variety of opportunistic microbes appear The first symptoms often include moderate and unexplained weight loss recurring respiratory tract infections such as sinusitis bronchitis otitis media pharyngitis prostatitis skin rashes and oral ulcerations Common opportunistic infections and tumors most of which are normally controlled by robust CD4 T cell mediated immunity then start to affect the patient Typically resistance is lost early on to oral Candida species and to Mycobacterium tuberculosis which leads to an increased susceptibility to oral candidiasis thrush and tuberculosis Later reactivation of latent herpes viruses may cause worsening recurrences of herpes simplex eruptions shingles Epstein Barr virus induced B cell lymphomas or Kaposi s sarcoma Pneumonia caused by the fungus Pneumocystis jirovecii is common and often fatal In the final stages of AIDS infection with cytomegalovirus another herpes virus or Mycobacterium avium complex is more prominent Not all patients with AIDS get all these infections or tumors and there are other tumors and infections that are less prominent but still significant Pathophysiology Transmission Estimated per act risk for acquisition of HIV by exposure route Exposure Route Estimated infections per 10 000 exposures to an infected source Blood Transfusion 9 000 Childbirth 2 500 Needle sharing injection drug use 67 Percutaneous needle stick 30 Receptive anal intercourse 50 Insertive anal intercourse 6 5 Receptive penile vaginal intercourse 10 Insertive penile vaginal intercourse 5 Receptive oral intercourse 131 Insertive oral intercourse 0 531 assuming no condom use source refers to oral intercourse performed on a man best guess estimate Three main transmission routes for HIV have been identified HIV 2 is transmitted much less frequently by the mother to child and sexual route than HIV 1 Sexual The majority of HIV infections are acquired through unprotected sexual relations Sexual transmission can occur when infected sexual secretions of one partner come into contact with the genital oral or rectal mucous membranes of another In high income countries the risk of female to male transmission is 0 04 per act and male to female transmission is 0 08 per act For various reasons these rates are 4 to 10 times higher in low income countries The correct and consistent use of latex condoms reduces the risk of sexual transmission of HIV by about 85 However spermicide may actually increase the transmission rate A meta analysis of 27 observational studies conducted prior to 1999 in sub Saharan Africa indicated that male circumcision reduces the risk of HIV infection However a subsequent review indicated that the correlation between circumcision and HIV in these observational studies may have been due to confounding factors In addition concerns were raised about the potential for spread of HIV by unsterilized blades during ritual circumcision Later trials in which uncircumcised men were randomly assigned to be medically circumcised in sterile conditions and given counseling and other men were not circumcised have been conducted in South Africa Kenya and Uganda showing reductions in female to male sexual HIV transmission of 60 53 and 51 respectively As a result a panel of experts convened by WHO and the UNAIDS Secretariat has recommended that male circumcision now be recognized as an additional important intervention to reduce the risk of heterosexually acquired HIV infection in men Studies of HIV among women who have undergone female genital cutting FGC have reported mixed results for details see Female genital cutting HIV Blood or blood product In general if infected blood comes into contact with any open wound HIV may be transmitted This transmission route can account for infections in intravenous drug users hemophiliacs and recipients of blood transfusions though most transfusions are checked for HIV in the developed world and blood products It is also of concern for persons receiving medical care in regions where there is prevalent substandard hygiene in the use of injection equipment such as the reuse of needles in Third World countries Health care workers such as nurses laboratory workers and doctors have also been infected although this occurs more rarely Since transmission of HIV by blood became known medical personnel are required to protect themselves from contact with blood by the use of universal precautions People who give and receive tattoos piercings and scarification procedures can also be at risk of infection HIV has been found at low concentrations in the saliva tears and urine of infected individuals but there are no recorded cases of infection by these secretions and the potential risk of transmission is negligible It is not possible for mosquitoes to transmit HIV Mother to child The transmission of the virus from the mother to the child can occur in utero during pregnancy intrapartum at childbirth or via breast feeding In the absence of treatment the transmission rate up to birth between the mother and child is around 25 However where combination antiretroviral drug treatment and Cesarian section are available this risk can be reduced to as low as one percent Postnatal mother to child transmission may be largely prevented by complete avoidance of breast feeding however this has significant associated morbidity Exclusive breast feeding and the provision of extended antiretroviral prophylaxis to the infant are also efficacious in avoiding transmission Multiple infection Main article HIV superinfection Unlike some other viruses infection with HIV does not provide immunity against additional infections particularly in the case of more genetically distant viruses Both inter and intra clade multiple infections have been reported and even associated with more rapid disease progression Multiple infections are divided into two categories depending on the timing of the acquisition of the second strain Coinfection refers to two strains that appear to have been acquired at the same time or too close to distinguish Reinfection or superinfection is infection with a second strain at a measurable time after the first Both forms of dual infection have been reported for HIV in both acute and chronic infection around the world Structure and genome Main article Structure and genome of HIV Diagram of HIV HIV is different in structure from other retroviruses It is roughly spherical with a diameter of about 120 nm around 60 times smaller than a red blood cell yet large for a virus It is composed of two copies of positive single stranded RNA that codes for the virus s nine genes enclosed by a conical capsid composed of 2 000 copies of the viral protein p24 The single stranded RNA is tightly bound to nucleocapsid proteins p7 and enzymes needed for the development of the virion such as reverse transcriptase proteases ribonuclease and integrase A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle This is in turn surrounded by the viral envelope that is composed of two layers of fatty molecules called phospholipids taken from the membrane of a human cell when a newly formed virus particle buds from the cell Embedded in the viral envelope are proteins from the host cell and about 70 copies of a complex HIV protein that protrudes through the surface of the virus particle This protein known as Env consists of a cap made of three molecules called glycoprotein gp 120 and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope This glycoprotein complex enables the virus to attach to and fuse with target cells to initiate the infectious cycle Both these surface proteins especially gp120 have been considered as targets of future treatment

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