HIV Epidemiology and Pathogenesis PDF

Epidemiology and pathogenesis 1425 37 ‘probable diagnosis’ may be made if the patient has the appropriate in pregnancy. Sexual partners should be examined and treated if clinical picture, without evidence of syphilis or HSV. infe...

Epidemiology and pathogenesis 1425 37 ‘probable diagnosis’ may be made if the patient has the appropriate in pregnancy. Sexual partners should be examined and treated if clinical picture, without evidence of syphilis or HSV. infected. Testing for the other causes of genital ulcers should be under- taken (see Box 37.5) and should include an ulcer swab for HSV and Scabies TP PCR, an ulcer swab for C. trachomatis NAAT with genotyping for This is discussed on page 674. LGV if positive, and serology for syphilis, which should be repeated after the 3-month window period. A NAAT for N. gonorrhoeae and Further reading C. trachomatis on FVU, or a VVS, and serology for HIV should also British Association for Sexual Health and HIV (BASHH). BASHH Clinical be performed. Effectiveness Guidelines. BASHH; http://www.bashh.org/. Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl J Single-dose regimens include ceftriaxone 250 mg i.m. or azithro- Med 2015; 372:2039–2208. mycin 1 g orally. Multiple-dose regimens are ciprofloxacin 500 mg Chow EP, Danielewski JA, Fehler G et al. Human papillomavirus in young women with Chlamydia trachomatis infection 7 years after the Australian human twice daily for 3 days or erythromycin 500 mg four times daily for papillomavirus vaccination programme: a cross-sectional study. Lancet Infect Dis 7 days. Multiple-dose regimens should be used in HIV patients, 2015; 15:1314–1323. as treatment failures have been reported with single-dose therapy. Hofstetter AM, Rosenthal SL, Stanberry LR. Current thinking on genital herpes. Curr Opin Infect Dis 2014; 27:75–83. Patients should be advised to abstain from sex for at least 7 days Jensen JS. Mycoplasma genitalium: yet another challenging STI. Lancet Infect and be followed up at 3–7 days, when the ulcers should be healing. Dis 2017; 17:795–796. HIV-infected patients should be monitored closely, as healing may Korenromp EL, Rowley J, Alonso M et al. Global burden of maternal and congenital syphilis and associated adverse birth outcomes – estimates for 2016 be slower. Sexual partners should be notified, examined, tested and progress since 2012. PLOS One 2019; 14:e0211720; https://doi.org/10.1371/ and treated epidemiologically, as asymptomatic carriage has been journal.pone.0211720. Merin A, Pachankis JE. The psychological impact of genital herpes stigma. reported. J Health Psychol 2011; 16:80–90. Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: Donovanosis gonorrhoea and Mycoplasma genitalium. Nat Rev Urol 2017; 14:139–152. Donovanosis (also known as granuloma inguinale) is exceed- ingly rare and is confined to a few countries in South-east Asia, southern Africa, parts of India and Brazil. It is caused by Klebsiella HUMAN IMMUNODEFICIENCY granulomatis. VIRUS AND ACQUIRED Clinical features IMMUNODEFICIENCY SYNDROME Nodules at the site of inoculation develop into friable, non-painful ulcers or hypertrophic lesions that increase in size. There is enlarge- EPIDEMIOLOGY AND ment of the inguinal lymph nodes, which may ulcerate. PATHOGENESIS Diagnosis and management Epidemiology The diagnosis is made on the presence of Donovan bodies using Since the first description of AIDS in 1981 and identification of the Giemsa or Silver stains in scrapings or biopsies of the lesions. Don- causative organism, HIV, in 1983, more than 78 million people are ovan bodies are the encapsulated intracellular Gram-negative rods estimated to have been infected and 39 million people have died. of K. granulomatis visible within mononuclear cells. Screening for all At the latest estimate, 36.9 million people worldwide were living other STIs should be undertaken. with HIV infection (representing 0.8% of adults aged 15-49 years), Antibiotic treatment should be given for a minimum of 3 weeks of whom 21.7 million are accessing anti-retroviral therapy (ART). and until the lesions have healed. Regimens include azithromy- Highly active ART has dramatically reduced mortality for those who cin 1 g weekly or 500 mg daily, or doxycycline 100 mg twice daily. are able to access care, transforming HIV from a universally fatal Patients should be advised to abstain from sex for at least 3 weeks infection into a long-term, manageable condition, with a conse- and be followed up until the lesions have fully resolved. Sexual part- quent rise in global prevalence. Effective ART also reduces onward ners should be notified, examined and treated if necessary. transmission, and since 2001 new infections globally have fallen by 38%; there is, however, considerable geographical diversity, with Pediculosis pubis infection rates continue to rise in Eastern Europe and parts of Cen- The pubic louse (Phthirus pubis) is able to attach tightly to the tral Asia. HIV is a major contributor to the global burden of disease, pubic and coarse body hair. It can also attach to eyelashes and being the leading cause of disability-adjusted life-years for people eyebrows. It is host-specific and is transferred by close bodily con- aged 30–45 years and the leading cause of death for women aged tact. Although infestation may be asymptomatic, the most common 15–49 years. complaint is of itch due to hypersensitivity to the louse bites. In 2014 the United Nations Programme on HIV/AIDS (UNAIDS) established new global targets for a scale-up in HIV treatment to help Diagnosis and management end the AIDS epidemic by 2030.These ‘90-90-90’ ambitions are that: Lice may be seen on the pubic and body hairs. They resemble small 90% of all people living with HIV know their HIV status scabs or freckles but can be seen moving. The eggs (nits) are laid at 90% of people with diagnosed HIV infection receive sus- the hair base and are strongly adherent to the hairs. Screening for tained ART other STIs should include NAAT for N. gonorrhoeae and C. tracho- 90% of all people receiving ART achieve viral suppression. matis, and serology for syphilis and HIV. Treatment should be applied to all areas of the body, including HIV in sub-Saharan Africa facial hair if present. Permethrin 1% should be left on for 10 min- Sub-Saharan Africa remains the region most seriously affected by utes and malathion 0.5% should be left on for 12 hours. A sec- the HIV epidemic. While southern and eastern Africa is home to ond application is usually advised after 7 days. Permethrin is safe 6.2% of the global population, this figure includes over half of the 37 1426 Sexually transmitted infections and human immunodeficiency virus world’s population living with HIV, and 43% of new HIV infections Pathology each year occur in this region. Swaziland has the world’s highest Whom to test for HIV infection, and where to do it, are summarized prevalence of HIV, with 27.2% of adults aged 15–49 infected. In sub- in Box 37.9. Saharan Africa, HIV infection is almost twice as common in young women (average prevalence 3.2%) than in men (1.6%). The reasons Routes of acquisition behind this are complex. The predominant route of HIV transmission Despite the fact that HIV can be isolated from a wide range of body in the region is through heterosexual sexual intercourse. fluids and tissues, the majority of infections are transmitted sexu- Despite the scale of the challenge faced in this region, progress ally via semen, cervical secretions and blood. The most significant is being made towards the ‘90-90-90’ goals, with an estimated 2.9 marker for transmission risk is the HIV viral load, which is highest million people initiating anti-retroviral agents (ARVs) in the region in in acute infection and reduced by effective ART. HIV-associated 2017. stigma and discrimination, gender-based violence and, in some countries of the world, the legal position for those at especially high HIV in high-income countries risk can all impede access to appropriate services and increase the Although the rate of new diagnoses is falling in many higher-income risks of transmission and acquisition of HIV. countries, the prevalence of HIV is rising: for example, there has been a decline in new diagnoses in the UK since 2015, with 4363 Sexual intercourse (vaginal and anal) people newly diagnosed in 2017, but falling death rates and con- Globally, heterosexual intercourse accounts for the vast majority tinuing new infections mean that the total number of people living of infections, and coexistent STIs, especially those causing geni- with HIV continues to rise. In 2017, 101 600 people in the UK were tal ulceration, enhance transmission. Passage of HIV appears to be estimated to be living with HIV; of these, 92% had received the more efficient from men to women, and to the receptive partner in diagnosis and 98% of those diagnosed were on treatment, of whom anal intercourse, than vice versa. Once the viral load is consistently 97% were virally suppressed. reduced below the limit of detection by effective ART, HIV cannot The fall in new infection rates is due to a combination of factors, be transmitted to sexual partners. Male circumcision has been including increased and repeat testing, rapid initiation of effective shown to reduce both acquisition and transmission. In the UK, sex therapy for those testing HIV-positive, and greater use of pre- between men accounts for over half of the new diagnoses reported exposure prophylaxis (PrEP) for those who are HIV-negative but at but there is a consistent rate of heterosexual transmission. In Cen- significant risk of acquiring the virus (see p. 1449). Of those diag- tral and sub-Saharan Africa, the epidemic has always been hetero- nosed with HIV in the UK, MSM and heterosexual populations from sexual, and more than half of HIV-positive adults in these regions sub-Saharan Africa are the two largest groups of people living with are women. South-east Asia and the Indian subcontinent are expe- the disease; 30% are women. As mortality rates fall, the population riencing an explosive epidemic, driven by heterosexual intercourse living with HIV is becoming older, with more than 1 in 3 now aged and a high incidence of other STIs. 50 years and over. Late diagnosis is the most common cause of HIV-related mor- Vertical transmission (transplacental, perinatal, bidity and mortality in the UK. Although the number of people diag- breast-feeding) nosed late (with a CD4 count of 1%) are two types, HIV-1 and HIV-2. HIV-1 is the most frequently occur- Men and women who report sexual contact abroad or in the UK with ring strain globally. HIV-2 is almost entirely confined to West Africa, individuals from countries of high HIV prevalence although there is some spread to Europe, particularly France and Patients presenting for healthcare when HIV enters the differential Portugal. HIV-2 has only 40% structural homology with HIV-1 and, diagnosis (see Box 37.10) although associated with immunosuppression and AIDS, appears HIV-associated indicator conditions to take a more indolent course than HIV-1. Many of the drugs that Respiratory are used in HIV-1 are ineffective in HIV-2. The structure of HIV is Tuberculosis, Pneumocystis jirovecii pneumoniaa, bacterial pneumonia, shown in Fig. 37.10. aspergillosis Retroviruses are characterized by possession of the enzyme Neurology reverse transcriptase, which allows viral RNA to be transcribed into Cerebral toxoplasmosisa, primary cerebral lymphomaa, cryptococcal DNA and then incorporated into the host cell genome. Reverse meningitisa, progressive multifocal leucoencephalopathya, aseptic meningitis/ transcription is an error-prone process with a significant rate of encephalitis, cerebral abscess, space-occupying lesion of unknown cause, mis-incorporation of bases. This, combined with a high rate of viral Guillain–Barré syndrome, transverse myelitis, peripheral neuropathy, dementia Dermatology 5HYHUVH SPDWUL[ Kaposi’s sarcomaa, severe/recalcitrant seborrhoeic dermatitis, severe/ WUDQVFULSWDVH recalcitrant psoriasis, multidermatomal/recurrent herpes zoster Gastroenterology Persistent cryptosporidiosisa, oral candidiasis, oral hairy leukoplakia, chronic diarrhoea of unknown cause, weight loss of unknown cause, Salmonella, /LSLGOD\HU Shigella, Campylobacter, hepatitis B infection, hepatitis C infection Oncology Non-Hodgkin lymphomaa, anal cancer, anal intraepithelial dysplasia, lung cancer, seminoma, head and neck cancer, Hodgkin lymphoma, Castleman’s disease 51$ Gynaecology Cervical cancera, vaginal intraepithelial neoplasia, cervical intraepithelial neoplasia, grade 2 or above Haematology 3URWHDVH Any unexplained blood dyscrasia, including thrombocytopenia, neutropenia and lymphopenia Ophthalmology JS Cytomegalovirus retinitis, infective retinal diseases including JS herpesviruses and toxoplasma, any unexplained retinopathy JS  HQYHORSH SFRUH Ear, nose and throat Lymphadenopathy of unknown cause, chronic parotitis, lymphoepithelial Fig. 37.10 Structure of HIV. Two molecules of single-stranded parotid cysts RNA are shown within the nucleus. The reverse transcriptase polymerase converts viral RNA into DNA (a characteristic of Other retroviruses). The protease includes integrase (p32 and p10). The p24 Mononucleosis-like syndrome (primary HIV infection), pyrexia of unknown (core protein) levels can be used to monitor HIV disease. p17 is the origin, any lymphadenopathy of unknown cause, any sexually transmitted matrix protein; gp120 is the outer envelope glycoprotein, which binds infection to cell surface CD4 molecules; and gp41, a transmembrane protein, aAIDS-de昀椀ning condition. influences infectivity and cell fusion capacity. (From http://guidance.nice.org.uk/PH33; http://www.nice.org.uk/guidance/PH34; http://www.bhiva.org/HIVTesting2008.aspx.)  Clinical features of untreated HIV infection 1429 37 or CXCR4 co-receptors, is responsible for HIV entry into cells. Box 37.10 AIDS-defining conditions Although CCR5 CD4 memory T lymphocytes within all body sys- tems are susceptible to infection and depletion, those found in the Candidiasis of bronchi, trachea or lungs gastrointestinal tract are heavily infected early in the process. These Candidiasis, oesophageal lymphocytes become rapidly depleted, leading to compromised Cervical carcinoma, invasive mucosal immune function, and thus allowing microbial lipopolysac- Coccidioidomycosis, disseminated or extrapulmonary charides to enter the circulation. HIV infection that is independent Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (1-month duration) of CD4 receptors can occur in astrocytes and renal epithelial cells, Cytomegalovirus (CMV) disease (other than liver, spleen or nodes) leading to end-organ damage. CMV retinitis (with loss of vision) Studies of viral turnover have demonstrated a virus half-life in the Encephalopathy, HIV-related circulation of about 6 hours. To maintain observed levels of plasma Herpes simplex, chronic ulcers (1-month duration), or bronchitis, viraemia, 108–109 virus particles need to be released and cleared pneumonitis or oesophagitis daily. Virus production by infected cells lasts for about 2 days and is Histoplasmosis, disseminated or extrapulmonary probably limited by the death of the cell, owing to direct HIV effects. Isosporiasis, chronic intestinal (1-month duration) This links HIV replication to the process of CD4 destruction and Kaposi’s sarcoma depletion. Progressive loss of activated CD4 T lymphocytes due to Lymphoma, Burkitt killing by CD8 cells is a key factor in the immunopathogenesis of Lymphoma, immunoblastic (or equivalent term) Lymphoma (primary) of brain HIV. Natural killer cells are involved in the host immune response, Mycobacterium avium-intracellulare complex or M. kansasii, although escape mutations within the virus population compro- disseminated or extrapulmonary mise their antiviral effects. The production of neutralizing antibod- Mycobacterium tuberculosis, any site ies, which, in some people, can be against several viral subtypes, Mycobacterium, other species or unidenti昀椀ed species, disseminated or occurs at about 12 weeks after infection. extrapulmonary Resulting cell-mediated immunodeficiency leaves the host open Pneumocystis jirovecii pneumonia to infections with intracellular pathogens, while coexisting antibody Pneumonia, recurrent abnormalities predispose to infections with capsulated bacteria. Progressive multifocal leucoencephalopathy HIV is associated with immune activation, a long-term inflam- Salmonella septicaemia, recurrent matory state, which is a key driver of disease progression. T-cell Toxoplasmosis of brain Wasting syndrome, due to HIV activation is observed from the earliest stages of infection, which, in turn, leads to an increase in the numbers of susceptible CD4- bearing target cells that can become infected and destroyed. This inflammatory state is associated with HIV itself, with co-pathogens Box 37.11 Summary of the Centers for Disease Control such as cytomegalovirus, and with the translocation of microbial (CDC) classification of HIV infection products, in particular lipopolysaccharides, from the gut into the Absolute A B C systemic circulation following HIV destruction of normal mucosal CD4 count immunity. Raised levels of inflammatory cytokines and coagula- Asymptomatic or HIV-related Clinical conditions (/mm3) persistent generalized conditions,a listed in AIDS tion system activation occur. These inflammatory responses may lymphadenopathy or not A or C surveillance case remain, despite effective ART, and play a role in HIV-associated acute seroconversion definition (see end-organ damage, as well as raising the risks of myocardial infarc- illness Box 37.10) tion and some malignancies. >500 A1 B1 C1 200–499 A2 B2 C2 Further reading