HUMAN IMMUNODEFICIENCY

VIRUS (HIV)
&
SEXUALLY TRANSMITTED
INFECTIONS (STI)
 HUMAN
IMMUNODEFICIENCY VIRUS
(HIV)
 EPIDEMIOLOGY AND
PATHOGENESIS
Since the first description of AIDS in 1981 and identification of the causative organism, HIV,
in 1983, more than 78million people are estimated to have been infected and 39million people have
died.
At the latest estimate, 37.9million people worldwide were living with HIV infection
(representing 0.8% of adults aged 15-49 years), of whom 21.7 million are accessing anti-retroviral
therapy (ART).
HIV is a major contributor to the global burden of disease, being the leading cause of
disability-adjusted life-years for people aged 30–45 years and the leading cause of death for women
aged 15–49 years.
Sub-Saharan Africa remains the region most seriously affected by the HIV epidemic. While
southern and eastern Africa is home to 6.2% of the global population, this figure includes over half
of the world’s population living with HIV, and 43% of new HIV infections each year occur in this
region.
WHERE DID HIV
COME FROM?
History of HIV
HIV infection in humans came from a type of chimpanzee in Central Africa.
The chimpanzee version of the virus (called simian immunodeficiency virus, or SIV) was
probably passed to humans when humans hunted these chimpanzees for meat and came in contact
with their infected blood.
Studies show that HIV may have jumped from chimpanzees to humans as far back as the late
1800s.
Over decades, HIV slowly spread across Africa and later into other parts of the world. We know
that the virus has existed in the United States since at least the mid to late 1970s.
1981
June 5: The U.S. Center for Disease Control (CDC)
publishes an article in (MMWR): Pneumocystis
Pneumonia—Los Angeles.
The article describes cases of a rare lung
infection,Pneumocystis carinii pneumonia(PCP), in
five young, white, previously healthy gay men in Los
Angeles.CDC’s Dr’s. reports that all the men have other
unusual infections as well, indicating that their immune
systems are not working. Two have already died by the
time the report is published and the others will die soon
after. This edition of the MMWR marks the first official
reporting of what will later become known as the AIDS
(Acquired Immunodeficiency Syndrome) epidemic.
 In 1983, Françoise Barré-Sinoussi and Luc Montaigner discovered a retrovirus in patients with swollen
lymph glands that attacked lymphocytes - a kind of blood cell that is very important to the body's immune
system.
The retrovirus, later named Human Immunodeficiency Virus (HIV), proved to be the cause of the
immunodeficiency disease AIDS. This discovery has been crucial in radically improving treatment methods
for AIDS sufferers.
ETIOLOGIC AGENT
● HIV: a human retrovirus belonging to the lentivirus family
● Two genetically different but related forms of virus have been
isolated.
● HIV-1: most common type seen in SUA, Europe and Central Africa
● HIV-2: primarily seen in West Africa.
FIGURE 197-1 A phylogenetic tree based on the nearly complete genomes (gag through nef genes) of primate immunodeficiency viruses. The scale (0.25) indicates a 25%
phylogenetically corrected genetic distance at the nucleotide level. Clades in color represent viruses (HIV-1, HIV-2) identified in humans after relatively recent transfers from
chimpanzee, gorilla, and sooty mangabey reservoirs. (Prepared by Brian Foley, PhD, of the HIV Sequence Database, Theoretical Biology and Biophysics Group, Los Alamos
National Laboratory; additional information at www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes.html.)
Structure of HIV
● Two molecules of single-stranded
RNA are shown within the nucleus.

● The reverse transcriptase polymerase converts viral

RNA into DNA

● The protease includes integrase.

● The p24 (core protein) levels can be used to

monitor HIV disease.
● p17 is the matrix protein;
● gp120 is the outer envelope glycoprotein,
which binds to cell surface CD4 molecules;
● gp41, a transmembrane protein,
influences infectivity and cell fusion capacity
Early HIV infection: incubation,
seroconversion and acute illness
● Early infection refers to the 6-month period following HIV acquisition, and is marked by
rapid viral replication resulting in high levels of HIV circulating in the plasma and genital
tract, and consequently by high infectiousness.
● This time is increasingly recognized as a key period for intervention, both to reduce
long-term sequelae and to cut onward transmission.
● Several HIV classification systems exist, the two most frequently used being the WHO
and Centers for Disease Control (CDC) classification. Their major application is in
public health monitoring and surveillance rather than in routine clinical care.
● The CDC classification (Stages 0–3) includes a combination of HIV-positive
laboratory results, the CD4 count and the presence of clinical AIDS defining conditions.
Immunological and clinical markers in combination with a positive HIV antibody test
are incorporated in the WHO classification system.
Symptomatic HIV infection
As HIV infection progresses, the viral load rises, the CD4 count falls and the patient
develops an array of symptoms and signs. The clinical picture is due to:
• the direct result of HIV causing end-organ damage
• the result of HIV-associated immunosuppression.
End-organ effects of HIV
Neurological disease
● Infection of the nervous tissue occurs at an early stage and clinical neurological
involvement increases as HIV advances. Manifestations include AIDS dementia complex
(ADC), sensory polyneuropathy and aseptic meningitis. These conditions have become
much less common since the introduction of ART.
Eye disease
● Eye pathology may occur in the later stages of infection. The most serious condition is
cytomegalovirus retinitis, which is sight-threatening.
Mucocutaneous manifestations
The skin is a common site for HIV-related pathology, as the function of dendritic and Langerhans cells,
both target cells for HIV, is disrupted.
Pruritus is a common complaint at all stages of HIV. Generalized dry, itchy, flaky skin is typical and
the hair may become thin and dry.
Hematological complications
These are common in advanced HIV infection.
● Lymphopenia progresses as the CD4 count falls.
● Anaemia of chronic HIV infection is usually mild, normochromic and normocytic.
● Neutropenia is common and usually mild.
● Isolated thrombocytopenia may occur early in infection and
be the only manifestation of HIV for some time.
● Pancytopenia
● Other complications involve myelotoxic drugs, which include
lamivudine (anaemia, neutropenia), ganciclovir (neutropenia),
systemic chemotherapy (pancytopenia) and co-trimoxazole
(agranulocytosis).
Gastrointestinal effects
●Weight loss and diarrhoea are common in people with
advanced untreated HIV infection.
●Hypochlorhydria is reported in patients with advanced HIV
disease and may have consequences for drug absorption and
bacterial overgrowth in the gut.
●Rectal lymphoid tissue cells are the targets for HIV infection
during penetrative anal sex and may be a reservoir for infection
to spread through the body.
Renal complications
● HIV-associated nephropathy (HIVAN; see p. 1356), although rare, can cause
significant renal impairment, particularly in more advanced disease.
● Other renal pathology seen in HIV includes HIV-immune complex kidney
disease (HIVICK), which can present with a range of glomerular abnormalities,
IgA nephropathy and thrombotic microangiopathy (TMA).
● Many nephrotoxic drugs are used in the management of HIV associated
pathology: for example, foscarnet, amphotericin B, pentamidine and
sulfadiazine. Tenofovir is associated with Fanconi’s syndrome
Respiratory complications

● Lymphoid interstitial pneumonitis (LIP) is well described in paediatric HIV

infection but is uncommon in adults. There is an infiltration of lymphocytes, plasma
cells and lymphoblasts in alveolar tissue. Epstein–Barr virus may be present. The
patient presents with dyspnoea and a dry cough, which may be confused with
Pneumocystis infection.
Endocrine complications

● Various endocrine abnormalities have been reported, including reduced

levels of testosterone and abnormal adrenal function.
The latter assumes clinical significance in advanced disease when intercurrent
infection superimposed on borderline adrenal function precipitates clear
adrenal insufficiency, requiring replacement doses of gluco- and
mineralocorticoid. Cytomegalovirus is also implicated in adrenal-deficient
states.
Cardiac complications
● Ischaemic heart disease was more common in those who took intermittent
ARV therapy than in those who maintained viral suppression.
● Cardiomyopathy has been associated with HIV and may lead to congestive
cardiac failure, although, in the ART era, cardiomyopathy related to
ischaemic disease is becoming more common.
● Lymphocytic and necrotic myocarditis has been described. In cases of
diagnostic uncertainty, ventricular biopsy can be undertaken to ensure that
other treatable causes of myocarditis are excluded.
Conditions associated with HIV
immunodeficiency
Immunodeficiency allows the development of opportunistic infections.
Susceptibility increases as the patient becomes more immunosuppressed, and CD4 T-
lymphocyte numbers are used as markers to predict the risk of infection. Patients with CD4
counts of more than 200 cells/mm3 are at low risk for the majority of AIDS defining conditions
while a hierarchy of thresholds for specific infectious risks can be constructed as the CD4 count
falls.
Baseline assessment investigations for a newly diagnosed
asymptomatic patient with HIV infection
An approach to sick HIV-positive patients
Monitoring
● Patients are regularly monitored, depending on clinical, virological and treatment
stage
● For people with HIV who have chosen not to initiate therapy, monitoring should
take place 2–4 times per year, with longer intervals for those with higher CD4 counts,
to assess progression of the infection and to discuss treatment options.
Immunological monitoring
● Absolute numbers (and relative proportions) of CD4 lymphocytes are monitored.
● The absolute CD4 count and its percentage of total lymphocytes fall as HIV progresses.
● Patients with counts of less than 200cells/mm3 are at greatest risk.
● Rapidly falling CD4 counts and those at or below 350 cells/mm are an
indication for immediate initiation of ART.
● Factors other than HIV (e.g. smoking, exercise, intercurrent infections and diurnal
variation) also affect CD4 numbers.
● Once the patient is virologically stable on ART with a CD4 above 350 cells/mm, CD4
counts are performed at approximately yearly intervals.
Virological monitoring
● The HIV viral load (HIV RNA) is monitored, which has both prognostic and therapeutic
value.
● HIV replicates at a high rate throughout the course of infection, many billions of new
virus particles being produced daily.
● The rate of viral clearance is relatively constant in any individual and thus the level of
viraemia is a reflection of the rate of virus replication.
Three HIV RNA assays for viral load are in current use:
• branched-chain DNA (bDNA)
• reverse transcription polymerase chain reaction (RT-PCR)
• nucleic acid sequence-based amplification (NASBA).
● HIV RNA is the standard marker of anti-retroviral treatment efficacy.
Management of HIV-positive patients
● The treatment of HIV using ART continues to evolve
and improve.
●Increased potency, reduced toxicity, greater convenience
of formulation, and availability of compounds with different mechanisms of action,
coupled with a better understanding of drug resistance, have combined to improve HIV
clinical and virological outcomes consistently.
● With increasing numbers of compounds now available as generics, some drug costs are
falling, and commissioners are increasingly focusing on the cost-effectiveness of the
newer agents to justify their use.
Anti-retroviral drugs (ARVs) commonly used in clinical
practice
 Prescribing anti-retroviral drugs (ARVs):
practice points
Monitoring patients on anti-retroviral
therapy (ART)
Treatment failure
● Failure of ART – that is, persistent viral replication causing immunological deterioration and eventual
clinical evidence of disease progression – is caused by a variety of factors, such as poor adherence, limited
drug potency, and food or other medication that may compromise drug absorption.

Changing therapy
● A rise in viral load, new clinical events that imply progression of HIV infection or the development of new
co-morbidities are all reasons to review therapy.
● Virological failure – that is, two consecutive viral loads of over 400 copies/mL in a previously fully
suppressed patient – requires investigation.
● Viral genotyping should be used to help select future therapy, choosing at least two new agents to which the
virus is fully sensitive.
● If a new suitable treatment option is available, it should be started as soon as possible.

Stopping therapy
● ARVs may have to be stopped if there is, for example, cumulative toxicity or potential drug interactions with
medications needed to deal with another more pressing problem. If adherence is poor, stopping completely
may be preferable to continuing with inadequate dosing, in order to reduce the development of viral resistance.
PREVENTION
&
CONTROL OF
HIV
INFECTION