Oxford Handbook of Genitourinary Medicine, HIV, and Sexual
Health (2 edn)
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History
In 1981 an epidemic of a previously unknown acquired immune deficiency syndrome (AIDS) was described in the USA. A lentivirus (subfamily of retroviruses) was subsequently identified. Lentus (from the Latin for slow) denotes the long latent phase between infection and the development of symptoms. Retroviruses use the enzyme reverse transcriptase (RT) to generate proviral DNA from RNA (reverse of the usual direction of genetic transcription). The term human immunodeficiency virus (HIV) was accepted in 1986. In the same year a related virus (HIV-2), endemic in West Africa and sharing common features including the induction of immune deficiency, was identified.
Origin of HIV
There are structural and genomic organizational similarities between HIV and simian immune deficiency virus (SIV). Phylogenetically, HIV-1 and HIV-2 cluster with chimpanzee (Pan troglodytes) (SIVcpz) and sooty mangabey (SIVsm) simian retroviruses, respectively. SIVcpz is almost identical to HIV-1.
The structural differences between HIV-1 and HIV-2 may explain the differences in natural history, pathogenicity, and susceptibility to anti-retroviral drugs.
Evidence that the virus existed for some time before its effects became clinically apparent in 1981 is supported by the following.
HIV detected in a blood sample taken in 1959 from an adult male living in the former Zaire. A different subtype was detected in a lymph node biopsy taken in 1960 from an adult female from the same country. Phylogenetic analysis of these two samples suggests that HIV may have crossed species some 35–75 years previously.
HIV found in tissue samples from an African American teenager who died in St Louis, USA, in 1969.
HIV found in tissue samples from a Norwegian sailor who died around 1976.
Prevalence
Worldwide (Table 35.1)
33 million people (15 million women and 2.5 million children under 15 years) were estimated living with HIV in 2007. Two-thirds of them are in sub-Saharan Africa. The estimated proportion of population infected with HIV has stabilized since 2001, mainly because of changes in high-risk behaviour and maturity of the pandemic in sub-Saharan Africa.
In the developed countries the number of people living with HIV is likely to because of migration, continuing transmission, and availability of life-prolonging drugs. Infection rates are likely to stay high in countries with poverty, inadequate healthcare, and limited resources for prevention. The socio-economic impact is greater in developing countries.
UK (Fig. 35.1)
Cumulative total of 93,000 reported cases of HIV in the UK by the end of 2007, with an estimated 73,000 living with HIV of whom one-third are unaware of their infection.
New infections have accelerated among ♂ who have sex with ♂ (MSM) since 1999, and by end of 2006 40% of people living with HIV were MSM.
Heterosexually acquired infections have been ↑ since the early years of the epidemic and outnumber those acquired through sex between ♂ since 1999. Over the past 10 years the migration of people into the UK from areas in the world with high HIV prevalence has contributed significantly to the increase in heterosexually transmitted infection. Injecting drug use plays a small role in the UK epidemic. The age at diagnosis of this group has risen, suggesting that new diagnoses are being made on a population mostly infected in the mid-1980s before widespread needle exchange programmes where introduced.
Screening blood donations and heat treatment of blood products to inactivate HIV was introduced in the UK in 1985. Since then there have been no recorded transmissions of HIV through contaminated clotting factors given to haemophilia patients. However, there have been five cases where HIV infection could have been acquired through blood transfusion. Current estimated blood transfusion risk in the UK is <1 in 1 million units.
UK HIV prevalence by risk factor. Source: From the Health Protection Agency 
www.hpa.org.uk
Heterosexuals | |
UK | |
North America, Western and Central Europe | 0.1–<1.0% |
Eastern Europe | 0.1–2% |
South America and Caribbean | 0.1–3% |
South, Eastern, Southeast Asia | <0.1–2% |
Oceania | <0.1–2% |
Middle East | <0.1–3% |
Africa | |
Southern | 20–28 |
Central and Eastern | 5–<15 |
Northern | <0.1–<0.5 |
Western | 1–<5 |
MSM | |
London | 15% |
Rest of UK | 2–3% |
Injecting drug users | |
London | 4.7% |
Rest of UK | 0.2% |
Heterosexuals | |
UK | |
North America, Western and Central Europe | 0.1–<1.0% |
Eastern Europe | 0.1–2% |
South America and Caribbean | 0.1–3% |
South, Eastern, Southeast Asia | <0.1–2% |
Oceania | <0.1–2% |
Middle East | <0.1–3% |
Africa | |
Southern | 20–28 |
Central and Eastern | 5–<15 |
Northern | <0.1–<0.5 |
Western | 1–<5 |
MSM | |
London | 15% |
Rest of UK | 2–3% |
Injecting drug users | |
London | 4.7% |
Rest of UK | 0.2% |
The viruses and their epidemiology
HIV-1 and HIV-2
HIV-1 and HIV-2 differ in several aspects.
HIV-1: found worldwide, a rapidly mutating virus eventually producing divergent quasi-species. More virulent and rapidly progressive than HIV-2.
HIV-2: predominantly found in West Africa but also reported in Portugal and France and increasingly in India and South America. Predominantly heterosexually transmitted. Lower viral loads (VLs) than HIV-1 independent of the duration of infection. Rate of vertical transmission ↓ than HIV-1.
HIV-1 and 2 are classified into groups according to their genetic diversity.
HIV-1
Group M (main group—90% of infection). Further divided into subtypes or clades with at least 11 genetically distinct subtypes: A1, A2, B, C, D, (E now considered a circulating recombinant form, RF01_AE), F1, F2, G, H, J, and K (I now classified as a CRF complex). Some variants are termed U category, i.e. uncertain or unclassifiable, and may represent new subtypes or recombinant forms. More than 40 circulating recombinant forms have been described so far and are likely to increase, as is their proportion in the pandemic.
Group O (outlier group).
Group N (new group).
HIV-2
Divided into groups: non-recombinant (A–G) and recombinant (AB).
Geographical distribution of HIV groups and subtypes
Group M is the most common group worldwide. The majority of its subtypes are found in Africa, while certain subtypes predominate in other regions.
Groups N and O are rare and remain confined to Western and Central Africa. Population movement and international travel will erode the geographical boundaries of subtype location.
Predominant subtype distribution
B—America, Europe, Australia, and Japan; Thailand and Southeast Asia (IV drug users). At least 25% of infections in Europe now are non-B subtypes.
A and D—sub-Saharan Africa.
C—Southern and Eastern Africa and India. Responsible for almost half of the infections worldwide.
E (CRF01_AE)—Thailand and Southeast Asia.
F—Brazil (also in Romania).
H—localized to Central Africa.
J—Central America.
Biological implications of HIV subtypes
Mode of transmission of HIV-1 subtypes:
subtype B is mainly found in MSM.
subtypes E (CRF01_AE) and C are more commonly seen in heterosexuals. They replicate more easily than subtype B in Langerhans’ cells (normally found in the vagina, cervix, and prepuce, but not in the rectum).
Infectivity: subtype E (CRF01_AE) is transmitted more easily than subtype B.
Natural history: subtype D causes more progressive disease than subtype A.
Response to therapy:
implications of subtype diversity need continuous assessment as they may influence the response to treatment
HIV-2 is intrinsically resistant to non-nucleoside RT inhibitors.
Vaccine production: unclear whether a vaccine provides subtype cross-protection. Genetic variations may be important and necessitate periodic vaccine modification (as with influenza vaccine).
Diagnosis and screening strategies: diagnostic tests must reliably detect the various strains, subtypes, and circulating recombinant forms. Modifications of tests can be made to ensure that all those with HIV infection are detected. This is also important for ensuring safety of the blood supply.
Phenotypic classification
HIV can also be classified on its ability to form a syncytium with CD4 cells in vitro. This ability is not directly related to the genotypic characteristic of the virus. Therefore, within each HIV subtype, there are isolates that are syncytium-inducing (SI) and non-syncytium-inducing (NSI). Most 1° HIV strains are NSI, while SI strains tend to appear with disease progression. This switch depends on cellular tropism for macrophages or T cells and on the chemokine co-receptor used to gain entry into the CD4 cell. Most NSI strains use CCR5 co-receptors and most SI strains use CXCR4 co-receptors.
Risk factors (Table 35.2) and routes of transmission
HIV is exclusively transmitted through body fluids. Routes of transmission include:
Sexual intercourse: between ♂ and ♀, ♂ and ♂, and rarely ♀ and ♀. Although sex between ♂ and ♂ characterized the initial HIV epidemic seen in the USA, Western Europe, and Australasia, elsewhere it is typically spread heterosexually. The relative risk of infection depends on the local prevalence and also the type of sexual practice.
Sharing infected needles and syringes among drug users.
Transfusion of blood and blood products: now very rare in countries where blood is screened for HIV. Transmission may still occur in the developing world through re-use of contaminated surgical equipment and needles.
Vertically from an infected mother to baby: antepartum, intrapartum, and postpartum (breastfeeding).
Occupational exposure: to healthcare professionals (HCP). Only one documented case of an HCP transmitting HIV to patients.
Sexual intercourse | |
Anal: receptive | 0.1–3% |
Anal: insertive | 0.06% |
Vaginal: receptive | 0.1–0.2% |
Vaginal: insertive | 0.03–0.09% |
Oral (fellatio): receptive | Up to 0.04% |
Oral: cunnilingus and insertive fellatio | No data but estimated to be at least half receptive rate |
Sharing injecting equipment | 0.7% |
Single unit of blood | 90–100% |
Occupational | |
Needlestick injury | 0.3% |
Mucous membrane contact | 0.1% |
Sexual intercourse | |
Anal: receptive | 0.1–3% |
Anal: insertive | 0.06% |
Vaginal: receptive | 0.1–0.2% |
Vaginal: insertive | 0.03–0.09% |
Oral (fellatio): receptive | Up to 0.04% |
Oral: cunnilingus and insertive fellatio | No data but estimated to be at least half receptive rate |
Sharing injecting equipment | 0.7% |
Single unit of blood | 90–100% |
Occupational | |
Needlestick injury | 0.3% |
Mucous membrane contact | 0.1% |
Influenced by plasma and genital VLs, breaks in mucosal surfaces (e.g. trauma, genital ulcer disease).
HIV (human immunodeficiency virus) is a virus which damages the body’s immune system. HIV destroys a type of white blood cell called the CD4 cell. This cell spearheads/leads the body’s defence against infection. When a person’s CD4 count becomes low he/she is more susceptible to certain infections.
AIDS (acquired immune deficiency syndrome) is the final stage of HIV infection. When the CD4 cells drop to a very low level (usually <200 cells/μL), the ability to resist certain infections is seriously impaired. Certain opportunistic conditions (AIDS-defining illnesses) can develop, e.g. Pneumocystis jiroveci (carinii) pneumonia (PCP), Kaposi’s sarcoma.
Having unprotected sex with an infected person.
Sharing a needle/equipment to take drugs.
Receiving a blood transfusion from an infected person (unlikely in the UK where blood has been tested for HIV since 1985).
Transmission from a positive mother to her baby during pregnancy or delivery, and by breastfeeding.
There is no evidence of transmission by kissing, and viral levels in saliva are very low. Body fluids which contain high levels of HIV correlating with infection are blood, seminal fluid, vaginal/menstrual fluid, and breast milk.
Yes, especially with receptive fellatio.
Some people have flu-like symptoms 4–8 weeks after infection. They usually settle within 1–2 weeks. A person can have HIV for many years before developing symptoms (and may never do so).
This depends on when your last risk activity was. An antibody test can be negative in the first few weeks after transmission. A further negative test at 3 months should confirm that transmission has not occurred
Although most infected people test positive within 2–6 weeks, it can take up to 3 months for enough antibodies to be produced to give a positive HIV antibody test. During this time the person is often very infectious with a high viral load.
