HIV, HHV-8, EBV, CMV, SARS-CoV2, AND PNEUMONIA
HUMAN IMMUNODEFICIENCY VIRUS (HIV)
GENERAL OVERVIEW
CLINICAL COURSE
The human immunodeficiency virus (HIV) was the most problematic virus before COVID-19 pandemic.
The clinical course of HIV infection presents specific features. Nowadays, this course is no longer
observed due to the presence of
antiretroviral therapies (ARTs) that
are able to stop HIV infection
progression towards AIDS.
The clinical course of the infection is
divided into three phases, which are:
• Acute phase: it is the first
phase, during which the CD4+
T cells decrease in number,
usually within the first 3-6
weeks; they drop from 1100-
1200/mm3 to 600-700/mm3;
then, they slightly increase in number (700-800/mm3), and they remain constant for several
years (clinical latency); during the acute phase the viraemia increases, up to reach a peak
during the slight increase of CD4+ T cell, to eventually decrease during the 12th week.
• Clinical latency: it is the second phase, in which the viraemia is generally low with a stable
plateau; this plateau correlates with the progression of the disease; the higher the viraemia,
the faster the progression to AIDS; as regards CD4+ T cells, they continue to decrease in the
number; this stage lasts from few years to 10-20 years, according to the viraemic levels.
• Acquired immunodeficiency syndrome (AIDS): it is the last phase; the viraemia levels increase
while the CD4+ T cell number significantly decrease; when there is a number of CD4+ T cell
lower than 200/mm3, AIDS is diagnosed; during this stage, there is a higher risk of
opportunistic infections; moreover, there is the development of clinical symptoms; the last
stage is death, which occurs with high viraemia and no CD4+ T cells.
As said before, there are new drugs (ARTs) used to upregulate the CD4+ T cell number, up to 600-
700/mm3; this is not the normal levels, but still avoid the progression of the disease, and maintain it
in the clinical latency.
HIV HISTORY
The HIV was firstly described in 1981 in California, where in several hospitals were reported several
homosexual patients, drug addicts, and blood transfusion patients who were suffering from
Pneumocystis carinii pneumonia, reactivation of
CMV, and oral or oesophageal candidiasis. All these
infections are uncommon in immunocompetent
patients, but instead are nowadays more common
in immunocompromised patients (e. g. oncological
patients, solid organ transplant patients). However,
40 years ago these infections were totally
uncommon.
In 1983 Gallo (discovered HTLV-1 and HTLV-2) and
Montagnier described the HIV virus, and they
correlated this virus with the diseases observed in
California. In 1999, the HIV/AIDS became the second most common disease in the world, after acute
lower respiratory infections.
,STAGES AND OPPORTUNISTIC INFECTIONS
The HIV infected patients are divided into three categories according to the CD4+ levels, which are:
• Acute infection: the CD4+ T cells >500/mm3; no symptoms are observed.
• Clinical latency: CD4+ T cells between
200-500/mm3
• AIDS: CD4+ T cells <200/mm3.
The infections associated with AIDS are:
• Cryptococcosis.
• Toxoplasmosis.
• Candidiasis.
• Tuberculosis.
• CMV reactivation.
• Pneumocystis jirovecii pneumonia.
• HSV reactivation.
• Progressive multifocal leukoencephalopathy (PML).
• Hodgkin lymphoma.
• Kaposi’s sarcoma.
• Cervical cancer.
TRANSMISSION AND LATE PRESENTERS
The incidence of HIV in Italy in 2022 was of 3.2:100,000 individuals. In the Veneto region about 8,000
patients are infected, and roughly 1,000 are added every year. The route of transmission can be of
four types, which are:
• Homosexual transmission.
• Heterosexual transmission.
• Injection-drug user
transmission: it was extremely
common in the past.
• Unknown transmission.
In Italy there is a good system of data
collection regarding the route of
transmission, and usually it is identified.
The two most common are heterosexual
(43.0%) and homosexual (40.9%)
transmission. In Western Europe and
Central Europe many routes of
transmission are unknown, while in
Eastern Europe the most common is the
heterosexual transmission.
The problem of HIV now is that it is not
spoken a lot regarding it, and therefore
the general population is less aware of
this infection. This result in an increased number of late presenters, who are defined as patients
diagnosed with HIV and CD4+ T cell <350/L (first infection acquired 7-10 years ago). These patients
represent 58.1% of new infection detected in Italy in 2022. In Europe they are about 50% of total HIV
patients.
The late presenters typically come to the hospital for some infectious disease, such as pneumonia,
meningitis, retinitis, and it is then found out that they are caused by opportunistic infections (e. g.
CMV, Pneumocystis jirovecii, etc.) that are observed only in HIV patients after years of latency.
Of these late presenters, 42% were diagnosed for AIDS; the remaining 58% were not AIDS.
, DISCOVERY OF HIV
The number of patients diagnosed with HIV is decreasing, but still, they are present. The number of
heterosexual infections remain steady, while the homosexual infections are increasing; the infections
due to shared injection drug syringes are
decreasing. The diagnosis of HIV in AIDS
patients is higher in older adults, since it is
required time to develop this disease.
Note that the HIV is a problem for both Italians
and foreigners. Indeed, it was observed that
two-third of the HIV infection occurs in Italians.
The diagnosis of HIV can occur for different
reasons, and the most common are suspicion of
HIV-related disease or HIV symptom (41.2%),
sexual behaviour at HIV infection (24.3%),
normal routine and screening test (8.9%),
blood donation (2%), and drug users (1.5%).
Note that to test for HIV there must be the patient’s consent. If the patient does not want to be tested,
you cannot go through. It is not required to give your name, and the test is free.
ACUTE INFECTION
The acute infection of HIV is presented as mild symptomatic or asymptomatic disease, with some
clinical features, which are:
• Fever.
• Adenopathy.
• Pharyngitis.
• Rash.
• Myalgia or arthralgia.
• Thrombocytopaenia.
• Leucopoenia.
• Diarrhoea.
• Headache.
• Encephalopathy: it is rare.
Therefore, this is presented as a flu-like
condition, and when patients present
these symptoms, they do not correlate them to HIV. After the symptom disappearance, which last
some days, patients are healthy, and they are unaware to their status. They will be latent for years, up
to reach the AIDS stage, in which symptoms and opportunistic infections appear.
HAART AND DIAGNOSIS
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
The life expectancy of HIV patients significantly increases with the introduction of highly active
antiretroviral therapy (HAART). At the beginning of the HIV history, a patient diagnosed with HIV at
25 years would die after 10-15 years. With the
introduction of HAART in 1997-1999 the overall
survival began to increase. The first patients to be
treated slightly increase their life expectancy, but
nowadays HIV patients can live until their 70s with
an OS of more than 75%.
Also, the type of drugs that were used is different.
Indeed, from drugs that should be taken 10 times
per day without some foods to increase the
HUMAN IMMUNODEFICIENCY VIRUS (HIV)
GENERAL OVERVIEW
CLINICAL COURSE
The human immunodeficiency virus (HIV) was the most problematic virus before COVID-19 pandemic.
The clinical course of HIV infection presents specific features. Nowadays, this course is no longer
observed due to the presence of
antiretroviral therapies (ARTs) that
are able to stop HIV infection
progression towards AIDS.
The clinical course of the infection is
divided into three phases, which are:
• Acute phase: it is the first
phase, during which the CD4+
T cells decrease in number,
usually within the first 3-6
weeks; they drop from 1100-
1200/mm3 to 600-700/mm3;
then, they slightly increase in number (700-800/mm3), and they remain constant for several
years (clinical latency); during the acute phase the viraemia increases, up to reach a peak
during the slight increase of CD4+ T cell, to eventually decrease during the 12th week.
• Clinical latency: it is the second phase, in which the viraemia is generally low with a stable
plateau; this plateau correlates with the progression of the disease; the higher the viraemia,
the faster the progression to AIDS; as regards CD4+ T cells, they continue to decrease in the
number; this stage lasts from few years to 10-20 years, according to the viraemic levels.
• Acquired immunodeficiency syndrome (AIDS): it is the last phase; the viraemia levels increase
while the CD4+ T cell number significantly decrease; when there is a number of CD4+ T cell
lower than 200/mm3, AIDS is diagnosed; during this stage, there is a higher risk of
opportunistic infections; moreover, there is the development of clinical symptoms; the last
stage is death, which occurs with high viraemia and no CD4+ T cells.
As said before, there are new drugs (ARTs) used to upregulate the CD4+ T cell number, up to 600-
700/mm3; this is not the normal levels, but still avoid the progression of the disease, and maintain it
in the clinical latency.
HIV HISTORY
The HIV was firstly described in 1981 in California, where in several hospitals were reported several
homosexual patients, drug addicts, and blood transfusion patients who were suffering from
Pneumocystis carinii pneumonia, reactivation of
CMV, and oral or oesophageal candidiasis. All these
infections are uncommon in immunocompetent
patients, but instead are nowadays more common
in immunocompromised patients (e. g. oncological
patients, solid organ transplant patients). However,
40 years ago these infections were totally
uncommon.
In 1983 Gallo (discovered HTLV-1 and HTLV-2) and
Montagnier described the HIV virus, and they
correlated this virus with the diseases observed in
California. In 1999, the HIV/AIDS became the second most common disease in the world, after acute
lower respiratory infections.
,STAGES AND OPPORTUNISTIC INFECTIONS
The HIV infected patients are divided into three categories according to the CD4+ levels, which are:
• Acute infection: the CD4+ T cells >500/mm3; no symptoms are observed.
• Clinical latency: CD4+ T cells between
200-500/mm3
• AIDS: CD4+ T cells <200/mm3.
The infections associated with AIDS are:
• Cryptococcosis.
• Toxoplasmosis.
• Candidiasis.
• Tuberculosis.
• CMV reactivation.
• Pneumocystis jirovecii pneumonia.
• HSV reactivation.
• Progressive multifocal leukoencephalopathy (PML).
• Hodgkin lymphoma.
• Kaposi’s sarcoma.
• Cervical cancer.
TRANSMISSION AND LATE PRESENTERS
The incidence of HIV in Italy in 2022 was of 3.2:100,000 individuals. In the Veneto region about 8,000
patients are infected, and roughly 1,000 are added every year. The route of transmission can be of
four types, which are:
• Homosexual transmission.
• Heterosexual transmission.
• Injection-drug user
transmission: it was extremely
common in the past.
• Unknown transmission.
In Italy there is a good system of data
collection regarding the route of
transmission, and usually it is identified.
The two most common are heterosexual
(43.0%) and homosexual (40.9%)
transmission. In Western Europe and
Central Europe many routes of
transmission are unknown, while in
Eastern Europe the most common is the
heterosexual transmission.
The problem of HIV now is that it is not
spoken a lot regarding it, and therefore
the general population is less aware of
this infection. This result in an increased number of late presenters, who are defined as patients
diagnosed with HIV and CD4+ T cell <350/L (first infection acquired 7-10 years ago). These patients
represent 58.1% of new infection detected in Italy in 2022. In Europe they are about 50% of total HIV
patients.
The late presenters typically come to the hospital for some infectious disease, such as pneumonia,
meningitis, retinitis, and it is then found out that they are caused by opportunistic infections (e. g.
CMV, Pneumocystis jirovecii, etc.) that are observed only in HIV patients after years of latency.
Of these late presenters, 42% were diagnosed for AIDS; the remaining 58% were not AIDS.
, DISCOVERY OF HIV
The number of patients diagnosed with HIV is decreasing, but still, they are present. The number of
heterosexual infections remain steady, while the homosexual infections are increasing; the infections
due to shared injection drug syringes are
decreasing. The diagnosis of HIV in AIDS
patients is higher in older adults, since it is
required time to develop this disease.
Note that the HIV is a problem for both Italians
and foreigners. Indeed, it was observed that
two-third of the HIV infection occurs in Italians.
The diagnosis of HIV can occur for different
reasons, and the most common are suspicion of
HIV-related disease or HIV symptom (41.2%),
sexual behaviour at HIV infection (24.3%),
normal routine and screening test (8.9%),
blood donation (2%), and drug users (1.5%).
Note that to test for HIV there must be the patient’s consent. If the patient does not want to be tested,
you cannot go through. It is not required to give your name, and the test is free.
ACUTE INFECTION
The acute infection of HIV is presented as mild symptomatic or asymptomatic disease, with some
clinical features, which are:
• Fever.
• Adenopathy.
• Pharyngitis.
• Rash.
• Myalgia or arthralgia.
• Thrombocytopaenia.
• Leucopoenia.
• Diarrhoea.
• Headache.
• Encephalopathy: it is rare.
Therefore, this is presented as a flu-like
condition, and when patients present
these symptoms, they do not correlate them to HIV. After the symptom disappearance, which last
some days, patients are healthy, and they are unaware to their status. They will be latent for years, up
to reach the AIDS stage, in which symptoms and opportunistic infections appear.
HAART AND DIAGNOSIS
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
The life expectancy of HIV patients significantly increases with the introduction of highly active
antiretroviral therapy (HAART). At the beginning of the HIV history, a patient diagnosed with HIV at
25 years would die after 10-15 years. With the
introduction of HAART in 1997-1999 the overall
survival began to increase. The first patients to be
treated slightly increase their life expectancy, but
nowadays HIV patients can live until their 70s with
an OS of more than 75%.
Also, the type of drugs that were used is different.
Indeed, from drugs that should be taken 10 times
per day without some foods to increase the
