and new infections are likely to continue declining.In June 1981, the USA Centers for Disease Control and Prevention reported a number of unusual infections and rare cancers in previously healthy young MSM. They all shared severe damage to the immune system and the acronym Acquired Immune Deficiency Syndrome (AIDS) was used for the first time in 1982. Previous research on animal viruses provided the basis for a USA group to publish their work in 1980 on the identification of a human T-cell leukaemia virus (later known as HTLV-1) as the first pathogenic human retrovirus. In 1981, the same group discovered HTLV-2 in a different T-cell type. HIV-1 was isolated in 1981 by a French group and, independently, by a USA group, and they published their research in the Lancet, April 1984, and Science, May 1984, respectively. The new virus isolates were collectively designated HTLV-3, a term no longer in use as the virus is officially called human immunodeficiency virus (HIV). HIV-2 was discovered in 1986.
HIV belongs to the genus lentivirus, a member of retroviruses family. Unlike other RNA viruses, retroviruses replicate their genome through a double-stranded viral DNA intermediate in the host nucleus.
• Zidovudine was approved by the USA Food and Drug Administration (FDA), as the first antiretroviral drug in March 1987.
• In 1988, 1 December was designated by WHO and supported by the UN as World AIDS Day.
• June 1995, the FDA approved the first protease inhibitor. (Saquinavir) ushering in a new era of highly active antiretroviral therapy (ART).
• June 1996, Nevirapine was the first non-nucleoside reverse transcriptase inhibitor (NNRTI) to be approved.
• The 11th International Conference on AIDS (Vancouver, July 1996) marked the first data to show evidence of (triple therapy) ART effectiveness and was quickly incorporated into clinical practice.
• October 2007, the FDA approved the first integrase inhibitor (Raltegravir).
• 2012, the FDA approved Truvada® for PrEP.
• In 2014, UNAIDS set the ‘90-90-90’ targets, aiming to diagnose 90% of all HIV positive people, provide ART for 90% of those diagnosed, and achieve undetectable HIV RNA for 90% of those on treatment by 2020.
• Treatment as prevention (TasP): there is enough evidence that patients on effective ART with an undetectable viral load cannot transmit HIV to others. Treatment as a tool for prevention is endorsed by many organizations.
• ‘Undetectable equals untransmittable’ (U=U) is a Consensus Statement produced by the Prevention Access Campaign. Backed by many organizations including the BHIVA and UNAIDS.
The reasons for the sudden emergence and the epidemic spread of HIV are still subjects of debate. Old World monkeys are infected with >40 different lentiviruses, simian immunodeficiency viruses (SIVs). They are largely non-pathogenic in their natural hosts. SIVmac causes immune deficiency in captive macaques (an Asian primate) and it is not a natural pathogen. Chimpanzees, sooty mangabey monkeys, and gorillas are natural hosts of SIVcpz, SIVsmm, and SIVgor, respectively; all of them are potential sources of human infection. Phylogenetically, HIV-1 is closely related to SIVcpz and HIV-2 to HIVsmm and SIVmac. Based on biological properties, and on phylogenetic and statistical analysis, transmission of these simian viruses to humans must have occurred through cutaneous or mucous membrane exposure of infected ape-blood and/or body fluids. Such exposure occurs most commonly in the context of bush meat hunting in central West Africa. Large scale vaccination campaigns at the beginning of the 20th century, together with rapid expansion of cities, disruption of the social structure, and increase rates of STIs, including genital ulcer disease, may have facilitated the dissemination and the adaptation of both HIV-1 and HIV-2.
HIV-1 is divided into 4 groups (M, N, O, and P) that were thought to have resulted from independent transmission events. Group M (major) was discovered first and is responsible for the pandemic. Molecular testing has dated the onset of group M and N (non-major) to the beginning of the 20th century. Groups O (outlier) and P are more recent. Genetic testing of infected blood and tissue samples collected from residents of Kinshasa (Democratic Republic of Congo) in 1959 and 1960, respectively, revealed that HIV had already diversified into different groups. Group M is further classified into 9 subtypes (A–D, F–H, J, and K), as well as >70 circulating recombinant forms (CRFs). A&D originated in central Africa, but established epidemics in eastern Africa. C was introduced to, and predominates in southern Africa, then spread to India and other Asian countries. Subtype B (accounts for the majority of HIV-1 in Europe and the Americas) arose from a single African strain that spread to Haiti in the 1960s then onwards to the USA and other western countries. CRF01 dominates in Southeast Asia.
HIV-1 is worldwide, whereas HIV-2 is restricted to West Africa (and countries with socio-economic links). HIV-2 is further divided into 8 groups (A–H), each represents an independent host transfer.
• HIV-2 is less aggressive and patients have lower viral loads. This leads to lower transmission rates and near complete absence of mother-to-child HIV transmission. Most infected patients do not progress to AIDS, but those who do show clinical disease indistinguishable from HIV-1.
• 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.
• The different geographical distribution may be a result of biological differences between types and subtypes.
• Group D has been associated with greater pathogenicity and increased incidence of cognitive impairment.
• HIV-2 is intrinsically resistant NNRTIs.
• Unclear whether a vaccine would provide subtype cross-protection.
• Diagnostic and screening tests must reliably detect all known types, subtypes, and CRFs.
See Table 37.1.
76.1 million people have become infected with HIV since the start of the epidemic, and 35.0 million people have died from AIDS-related illnesses since the start of the epidemic. UNAIDS estimated that by the end of 2016 there were 36.7 million people living with HIV (PLWH). In 2016, 1.8 million adults and children were newly infected, 64% of them are in sub-Saharan Africa. Due to availability of effective therapy and other strategies, the number of PLWH is likely to and new infections are likely to continue declining.
Table 37.1 UNAIDS 2016 figures
| Region | Number (in millions) |
| Asia and the Pacific | 5.1 |
| Eastern and Southern Africa | 19.4 |
| Eastern Europe and Central Asia | 1.6 |
| Latin America | 1.8 |
| Caribbean | 0.31 |
| Middle East and North Africa | 0.23 |
| Western and central Africa | 6.1 |
| Western and central Europe and North America | 2.1 |
• By the end of 2016, there were 89,400 PLWH in England, 11.6% of them were undiagnosed.
• 71% of males living with HIV were MSM.
• Due to changes in immigration patterns, there has been a continued decline in new HIV diagnoses among Black African heterosexual men and women in the past 10 years.
• New diagnoses were rising until 2015, followed by 18% decline in 2016.
• In 2016, new HIV diagnoses among MSM fell for the first time since the start of the epidemic.
• Late diagnosis remains a challenge. In 2016, 42% of diagnoses happened at a late stage of infection (CD4 count <350 cells/µL).
• In 2016, 96% of those diagnosed are accessing treatment and 94% are virally suppressed.
• One in three of PLWH accessing care are aged 50 years or older, and 5% are 65 or older.
HIV is exclusively transmitted through body fluids. Routes of transmission include:
• Sexual intercourse between women and men, men and men, and rarely women and women: sex between men and men is the major route of transmission in the USA, Western Europe, and Australia, elsewhere it is typically heterosexually spread.
• Sharing contaminated needles, syringes, and other equipment among drug users.
• Transfusion of blood and blood products: now very rare in countries where blood is screened for HIV. Transmission may occur in developing world through the re-use of contaminated surgical equipment and needles.
• Vertically from an infected mother to baby: antepartum, intrapartum, and post-partum (breastfeeding)
• Occupational: to HCW. In the UK there is only one documented case of a HCW transmitting HIV to patients.
Table 37.2 HIV transmission risk following a single exposure to HIV infection*
| 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 |
| Other | |
| 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 is a virus that damages the body’s immune system. HIV destroys a type of WBC 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 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), KS.
• 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 breastmilk.
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.
Delay between infection and a positive HIV antibody test
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 VL.