Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
PATHOGENESIS AND CLINICAL ASPECTS OF TROPICAL INFECTIOUS DISEASES
New “rules” since 2024-2025:
Wri6en exam = 70% ⇨ Open ques@ons, MCQ about lessons and student presenta@ons (NOT 75% anymore)
Presenta@on = 30% ⇨ 30 mins presenta@on, 15 minutes ques@ons, also discuss a research paper (NOT 25% anymore)
HIV/AIDS – A PANDEMIC WITH ZOONOTIC ORIGIN (KEVIN ARIËN)
ZOONOTIC ORIGIN OF HIV
Knowledge from ecological work: They collected fecal samples and used human serology test which detects specific
an@bodies against viral proteins so they were able to find out whether there were Ab to HIV. They also looked for the
actual HIV or SIV RNA in the samples, so not only immunology (PCR, sequencing…).
SIV = simian immunodeficiency virus
A phylogene;c tree containing HIV and SIV viruses for different monkeys shows rela@ons: HIV-2 is close to SIV in sooty
mangabey and HIV-1 is close to SIV in chimps (cpz) or gorillas (gor), thus they are presumable zoono;c reservoirs.
The origins of HIV-1 and HIV-2 can be traced back. They have different groups.
Virus HIV-1
Group M N O P
Source SIVcpz SIVcpz SIVgor SIVgor
Epidemic World No No No
Virus HIV-2
Group A, B C, D, E, F, G, H
Source SIVsmm SIVsmm
Epidemic West Africa No
Non-human primates are hunted and captured for prepara@on (bushmeat). Monkeys can also be cap@vated and kept as
pets. This forms a risk at infec@on. When looking at the prevalence of the SIV virus on monkey species and which are
sold on the bushmeat market: many of the monkeys that are sold for bushmeat or pets are also the ones that carry the
SIV virus!
HIV-1: FROM LOCAL OUTBREAK TO GLOBAL PANDEMIC
HIV jumped to humans in Cameroon (1884-1916) but it wasn’t un@l it got to Kinshasa (1920) that it really took off as a
pandemic. By 1950, there was already an extensive HIV variability in the Democra;c Republic of Congo (DRC) with
different subtypes. Thus, DRC is the suggested epicenter of the outbreak. There was also an increase of popula@on in
some of the major ci@es and together with the introduc@on of cases, it probably caused the
rapid spread of HIV in the DRC. In the southern part of DRC, Lubumbashi is located, where you
could find mines with copper, cobalt etc. During the Belgian colonial @mes, there was a railway
from Kinshasa to Lubumbashi to export minerals and to a6ract workers to the mines. Over half
a million miners were travelling from Kinshasa to Lubumbashi and during that @me there was
also more and more pros@tu@on. In the northern part of DRC, there were less railways, but
more transport via boats in the Congoriver. So, everything went slower, thus also to spread of
HIV.
Once HIV was established in DRC, there was also transmission to other parts in the world. By 1981, 5 cases were
described in Los Angeles of men having sex with men. When they did sequencing of the older samples, they saw a lot of
diversity and a lot of varia@on had already occurred in 1981. So, the outbreak started in Africa, then transferred to Hai@
and was further transmi6ed towards the United States. The widest diversity can be seen in West-Africa, as the virus as
been there for a very long @me. Subtype C is mostly seen in Southern-Africa and East-Africa, while subtype B is seen
mostly in America and Europe.
HIV TRANSMISSION
HIV transmission can happen via:
• Unprotected sexual intercourse with an infected partner
• Ver;cal transmission (mother to child)
o In utero
o During delivery
o Breastmilk
• Injec;on drug use
1
,Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
People transmit the virus when they have the highest viral loads. The virus keeps replica@ng and you build up a viral
load in the body, but also in the genital secre@ons. This occurs mostly during the early phase when they are not really
aware they have HIV. Then, when they no@ce they have HIV, they suppress the viral load in treatment. In cases of
untreated pa@ents, there is of course more risk of transmission.
HIV MUCOSAL TRANSMISSION AND SYSTEMIC DISSEMINATION
Haase, A. Targe2ng early infec2on to prevent HIV-1 mucosal transmission. Nature 464, 217–223 (2010).
https://doi.org/10.1038/nature08757
The virus can infect new individuals both in vaginal and cervical @ssue. The
vaginal epithelium is mul@layered and squamous, while the cervical epithelium
is single layered and columnar. If the epithelium is healthy, then there omen is
no problem. If the epithelium is disrupted (mechanical damage by sex, other
STDs), then infec@on can occur. The virus can get across of the cells and end up
in the mucosal @ssue. The target cells are the macrophages, dendri@c cells…
and are recruited because of the inflamma;on due to the disrupted epithelium.
Secre@on of cytokines and chemokines will a6ract more target cells to the site
and will create local pockets of infec@on. Not only disrup@on of epithelium and
pre-exis@ng inflamma@on contributes to transmission. Exposure of the cervical
vaginal epithelium to semen causes an increase in chemokines and pro-
inflammatory cytokines that recruit neutrophils, dendri@c cells, macrophages
and lymphocytes. Normally, the immune system would eliminate the infec@on,
but in some cases the virus can keep replica@ng and can infect dendri;c cells,
which will go to the lymph nodes where the infec@on will transfer to the T cells
as well. This results in a generalized infec;on instead of a localized infec@on in
the genital mucosa. Then, there is basically no way back.
GENETIC BOTTLENECK DURING (SEXUAL) TRANSMISSION
Within a few days, you will get a swarm of different mutants in the body (quasispecies). There will be a selec;on of
those which are fit for transmission and are sufficiently well-matched to replicate in the body. These are usually minor
variants in the quasispecies that have be6er proper@es to be selected for
transmission. So in this image it’s not the red ones but the light green ones, even
if they are less prevalent. However, remember that the epithelial lining could
also be bypassed with an injec@on needle, so then all the quasispecies will be in
the body.
In this graph you can also see in green the donor, with each line represen@ng a viral variant
and thus a lot of diversity. The blue ones are from the newly infected recipient. It’s typically
just one variant from the donor that shims to blue. The diversity in the recipient is much
smaller than in the donor.
Approximately 75% of pa@ents are infected by a single virus and 25% are infected by 2-5 viruses (mul@ple variants).
CHARACTERISTICS OF THE “TRANSMITTED VIRUS”
1. Mostly only a single “founder” virus (in 75%-80% of transmission cases)
Mul@ple gene@c variants: STIs, IV drug use, rectal transmission
2. CD4 and CCR5-tropic
3. Replicate in CD4+ T-lymphocytes, less efficient in macrophages
4. Shorter variable loop lengths (V1-V2)
5. Fewer N-linked glycosyla@on sites on the envelope
Correlates with more efficient binding to integrin-𝛼4β7 receptor
6. More resistant to early IFN responses
There is a high expression of CCR5 (secondary receptor) on GALT CD4+ (primary receptor) T-cells. A lot of immune cells
are located in the GALT (gut associated lymphoid @ssue). This is a good target for HIV infec@on.
2
,Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
THE MALE URO-GENITAL TRACT
The site of infec@on in men is mostly the inner foreskin, as it only has a thin layer of epithelium and contains many of
the HIV target cells, like DC, MF, Tcells. Circumcision protects men, but indirectly also their partners, because you
reduce the number of target cells. The glans penis has a cornified layer which gives you extra protec@on.
THE ANO-RECTAL MUCOSA
Infec@on happens mostly at the ano-rectal junc;on, because there is a shim from singular columnar epithelium of the
rectum to the mul@ple-layered squamous epithelium of the anus.
THE FEMALE GENITAL TRACT
The most vulnerable region is the transforma@on zone between endo- and ectocervix or squamo-columnar junc;on.
The endocervix is lined with single layer columnar epithelium and the ectocervix is layered with stra@fied squamous
epithelium. Cervical ectropion or ectopy is a condi@on in which endocervical material is s@cking out of the ectocervix,
so the cervix is more vulnerable. A woman omen has no symptoms, but will be more vulnerable for infec@on.
CORRELATES OF SHEDDING
Male: Urethri@s, genital ulcer disease, Trichomonas vaginalis, cytomegalovirus…
Female: Bacterial vaginosis, HSV-2, HPV, Chlamydia trachoma@s, Candida vulvovagini@s, Neisseria gonorrhoeae…
• Bacterial vaginosis: disbalance of lactobacilli (acid producing) which make up the normal healthy flora. This will
result in a less acidic environment so the protec@ve environment becomes compromised.
• STIs cause a thinned or damaged epithelium, providing access to target cells in the submucosal @ssue, which
are also a6racted by the inflamma@on.
A HEALTHY EPITHELIUM OFFERS PROTECTION AGAINST INFECTION
• Epithelium as a passive physical barrier
o Mul@layered vs single-layered Biological factors that reduce risk of HIV transmission
o Kera@nized vs non-kera@nized
o Protec@ve and immobilizing mucus
o Acidic vaginal pH
• Epithelium as an ac@ve front line of the immune system
o Innate defenses via Toll-like receptors
§ Defensins & an@microbial pep@des
§ Secretory leukocyte protease inhibitor (SLPI)
§ Lactoferrin, Lysozyme
§ Surfactant protein A
§ Complement
o Langerhans’ cells, @ssue-resident macrophages, recruitment of DC, T-cells
WHEN THINGS TURN BAD…
The innate and inflammatory responses directed against HIV can also enhance transmission. Because of the influx of
large numbers of HIV target cells (DC, MF, CD4+ Tcells…) driven by the inflammatory environment, there can be an
expansion of infec@on via cell-cell contacts.
STIs result in a thinned or damaged epithelium, providing direct access to target cells in the submucosal @ssue. This
results in a local inflammatory environment, which a6racts addi@onal immune/HIV target cells.
Bacterial vaginosis is a disbalanced environment of the vaginal Biological factors that increase risk of HIV transmission
microflora (lactobacilli). This causes a change in the normally acidic pH,
which normally has a protec@ve effect. It is also an increased risk for STI
acquisi@on.
3
, Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
HIV DISEASE COURSE
People transmit the virus when they have the highest viral loads. The virus keeps replica6ng and you build up a viral load in the body, but also in the genital
secre6ons. This occurs mostly during the early phase when they are not really aware they have HIV. Then, when they no6ce they have HIV, they suppress the
viral load in treatment. In cases of untreated pa6ents, there is of course more risk of transmission. (seen on page 2)
At first, people don’t know they are infected (eclipse phase).
HIV establishes the viral reservoir already, amer which remains
there for life. Amer ± 3 weeks, the virus can be detected in the
blood for the first @me and some symptoms arise. This is the
acute phase. In the chronic phase, the viral setpoint is
established and chronic inflamma@on occurs. The set point can
be higher or lower, for more-fit viruses, immune dysfunc@on
and high levels of inflamma@on or poorly fit viruses, stronger
immune responses and low levels of inflamma@on
respec@vely. The infec@on slowly progresses to AIDS.
The symptoms generally occur 5-30 days amer exposure and have a median dura@on of 14 days. Symptoms can be:
• Fever, fa@gue, malaise, arthralgias, headache, nausea, vomi@ng, diarrhea
• Lymphadenopathy, pharyngi@s, rash, weight loss, mucocutaneous ulcera@ons, asep@c meningi@s
• Leukopenia, thrombocytopenia, elevated liver enzymes
Amer 6 weeks, the body can recover a bit. The immune system tries to get
control over the virus and the CD4+ Tcell counts begin to rise again.
However, the viral load increases again, quasispecies are built. The CD4+
Tcell count will decrease again over the years. AIDS is established when the
CD4+ Tcell count is <200 cells/µl, and then there is a high risk of other
infec@ons.
The HIV disease course is variable. The progression of HIV, and thus the chronic phase, usually takes several years.
However, there are some excep@ons:
• Rapid progressor: These people do not really have a clinical latency. They establish AIDS and die amer months
or only a few years.
• Non-progressor: These people never progress to the final AIDS stage.
o These people are very interes@ng, because they seem to control the virus in a natural way. It is not
understood how this happens so it is important to inves@gate.
o If we can understand the underlying mechanisms of the non-progressors, we might find solu@ons or
even a cure.
HIV is a len;virus (retrovirus) so it integrates itself in the host genome. Once the virus infects the cell, it will integrate a
gene@c copy into our own genome and once it is there, it stays there. This happens before people realise they are
infected, show symptoms or even get treated. Once a person is infected, they are infected for life. Current treatments
are unable to cure the infec@on (because the integra@on in the genome). There is an ac@ve viral replica@on throughout
the course of the disease. ~10 billion virus par@cles are produced every day when untreated. The major reservoirs of
the virus are outside of the blood compartment: lympho-re@cular @ssues, bone marrow, lymph nodes, spleen, GALT,
CNS, genital tract.
HIV profoundly affects the immune system and leads to…
• Opportunis;c infec;ons
o Mycobacterium tuberculosis (see lecture by Leen Rigouts)
o Candidiasis, cryptococcosis, histoplasmosis (fungi)
o CMV, HSV
• Neurological symptoms
o Confusion, headaches, changes in behavior and vision, balance and coordina@on
4
PATHOGENESIS AND CLINICAL ASPECTS OF TROPICAL INFECTIOUS DISEASES
New “rules” since 2024-2025:
Wri6en exam = 70% ⇨ Open ques@ons, MCQ about lessons and student presenta@ons (NOT 75% anymore)
Presenta@on = 30% ⇨ 30 mins presenta@on, 15 minutes ques@ons, also discuss a research paper (NOT 25% anymore)
HIV/AIDS – A PANDEMIC WITH ZOONOTIC ORIGIN (KEVIN ARIËN)
ZOONOTIC ORIGIN OF HIV
Knowledge from ecological work: They collected fecal samples and used human serology test which detects specific
an@bodies against viral proteins so they were able to find out whether there were Ab to HIV. They also looked for the
actual HIV or SIV RNA in the samples, so not only immunology (PCR, sequencing…).
SIV = simian immunodeficiency virus
A phylogene;c tree containing HIV and SIV viruses for different monkeys shows rela@ons: HIV-2 is close to SIV in sooty
mangabey and HIV-1 is close to SIV in chimps (cpz) or gorillas (gor), thus they are presumable zoono;c reservoirs.
The origins of HIV-1 and HIV-2 can be traced back. They have different groups.
Virus HIV-1
Group M N O P
Source SIVcpz SIVcpz SIVgor SIVgor
Epidemic World No No No
Virus HIV-2
Group A, B C, D, E, F, G, H
Source SIVsmm SIVsmm
Epidemic West Africa No
Non-human primates are hunted and captured for prepara@on (bushmeat). Monkeys can also be cap@vated and kept as
pets. This forms a risk at infec@on. When looking at the prevalence of the SIV virus on monkey species and which are
sold on the bushmeat market: many of the monkeys that are sold for bushmeat or pets are also the ones that carry the
SIV virus!
HIV-1: FROM LOCAL OUTBREAK TO GLOBAL PANDEMIC
HIV jumped to humans in Cameroon (1884-1916) but it wasn’t un@l it got to Kinshasa (1920) that it really took off as a
pandemic. By 1950, there was already an extensive HIV variability in the Democra;c Republic of Congo (DRC) with
different subtypes. Thus, DRC is the suggested epicenter of the outbreak. There was also an increase of popula@on in
some of the major ci@es and together with the introduc@on of cases, it probably caused the
rapid spread of HIV in the DRC. In the southern part of DRC, Lubumbashi is located, where you
could find mines with copper, cobalt etc. During the Belgian colonial @mes, there was a railway
from Kinshasa to Lubumbashi to export minerals and to a6ract workers to the mines. Over half
a million miners were travelling from Kinshasa to Lubumbashi and during that @me there was
also more and more pros@tu@on. In the northern part of DRC, there were less railways, but
more transport via boats in the Congoriver. So, everything went slower, thus also to spread of
HIV.
Once HIV was established in DRC, there was also transmission to other parts in the world. By 1981, 5 cases were
described in Los Angeles of men having sex with men. When they did sequencing of the older samples, they saw a lot of
diversity and a lot of varia@on had already occurred in 1981. So, the outbreak started in Africa, then transferred to Hai@
and was further transmi6ed towards the United States. The widest diversity can be seen in West-Africa, as the virus as
been there for a very long @me. Subtype C is mostly seen in Southern-Africa and East-Africa, while subtype B is seen
mostly in America and Europe.
HIV TRANSMISSION
HIV transmission can happen via:
• Unprotected sexual intercourse with an infected partner
• Ver;cal transmission (mother to child)
o In utero
o During delivery
o Breastmilk
• Injec;on drug use
1
,Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
People transmit the virus when they have the highest viral loads. The virus keeps replica@ng and you build up a viral
load in the body, but also in the genital secre@ons. This occurs mostly during the early phase when they are not really
aware they have HIV. Then, when they no@ce they have HIV, they suppress the viral load in treatment. In cases of
untreated pa@ents, there is of course more risk of transmission.
HIV MUCOSAL TRANSMISSION AND SYSTEMIC DISSEMINATION
Haase, A. Targe2ng early infec2on to prevent HIV-1 mucosal transmission. Nature 464, 217–223 (2010).
https://doi.org/10.1038/nature08757
The virus can infect new individuals both in vaginal and cervical @ssue. The
vaginal epithelium is mul@layered and squamous, while the cervical epithelium
is single layered and columnar. If the epithelium is healthy, then there omen is
no problem. If the epithelium is disrupted (mechanical damage by sex, other
STDs), then infec@on can occur. The virus can get across of the cells and end up
in the mucosal @ssue. The target cells are the macrophages, dendri@c cells…
and are recruited because of the inflamma;on due to the disrupted epithelium.
Secre@on of cytokines and chemokines will a6ract more target cells to the site
and will create local pockets of infec@on. Not only disrup@on of epithelium and
pre-exis@ng inflamma@on contributes to transmission. Exposure of the cervical
vaginal epithelium to semen causes an increase in chemokines and pro-
inflammatory cytokines that recruit neutrophils, dendri@c cells, macrophages
and lymphocytes. Normally, the immune system would eliminate the infec@on,
but in some cases the virus can keep replica@ng and can infect dendri;c cells,
which will go to the lymph nodes where the infec@on will transfer to the T cells
as well. This results in a generalized infec;on instead of a localized infec@on in
the genital mucosa. Then, there is basically no way back.
GENETIC BOTTLENECK DURING (SEXUAL) TRANSMISSION
Within a few days, you will get a swarm of different mutants in the body (quasispecies). There will be a selec;on of
those which are fit for transmission and are sufficiently well-matched to replicate in the body. These are usually minor
variants in the quasispecies that have be6er proper@es to be selected for
transmission. So in this image it’s not the red ones but the light green ones, even
if they are less prevalent. However, remember that the epithelial lining could
also be bypassed with an injec@on needle, so then all the quasispecies will be in
the body.
In this graph you can also see in green the donor, with each line represen@ng a viral variant
and thus a lot of diversity. The blue ones are from the newly infected recipient. It’s typically
just one variant from the donor that shims to blue. The diversity in the recipient is much
smaller than in the donor.
Approximately 75% of pa@ents are infected by a single virus and 25% are infected by 2-5 viruses (mul@ple variants).
CHARACTERISTICS OF THE “TRANSMITTED VIRUS”
1. Mostly only a single “founder” virus (in 75%-80% of transmission cases)
Mul@ple gene@c variants: STIs, IV drug use, rectal transmission
2. CD4 and CCR5-tropic
3. Replicate in CD4+ T-lymphocytes, less efficient in macrophages
4. Shorter variable loop lengths (V1-V2)
5. Fewer N-linked glycosyla@on sites on the envelope
Correlates with more efficient binding to integrin-𝛼4β7 receptor
6. More resistant to early IFN responses
There is a high expression of CCR5 (secondary receptor) on GALT CD4+ (primary receptor) T-cells. A lot of immune cells
are located in the GALT (gut associated lymphoid @ssue). This is a good target for HIV infec@on.
2
,Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
THE MALE URO-GENITAL TRACT
The site of infec@on in men is mostly the inner foreskin, as it only has a thin layer of epithelium and contains many of
the HIV target cells, like DC, MF, Tcells. Circumcision protects men, but indirectly also their partners, because you
reduce the number of target cells. The glans penis has a cornified layer which gives you extra protec@on.
THE ANO-RECTAL MUCOSA
Infec@on happens mostly at the ano-rectal junc;on, because there is a shim from singular columnar epithelium of the
rectum to the mul@ple-layered squamous epithelium of the anus.
THE FEMALE GENITAL TRACT
The most vulnerable region is the transforma@on zone between endo- and ectocervix or squamo-columnar junc;on.
The endocervix is lined with single layer columnar epithelium and the ectocervix is layered with stra@fied squamous
epithelium. Cervical ectropion or ectopy is a condi@on in which endocervical material is s@cking out of the ectocervix,
so the cervix is more vulnerable. A woman omen has no symptoms, but will be more vulnerable for infec@on.
CORRELATES OF SHEDDING
Male: Urethri@s, genital ulcer disease, Trichomonas vaginalis, cytomegalovirus…
Female: Bacterial vaginosis, HSV-2, HPV, Chlamydia trachoma@s, Candida vulvovagini@s, Neisseria gonorrhoeae…
• Bacterial vaginosis: disbalance of lactobacilli (acid producing) which make up the normal healthy flora. This will
result in a less acidic environment so the protec@ve environment becomes compromised.
• STIs cause a thinned or damaged epithelium, providing access to target cells in the submucosal @ssue, which
are also a6racted by the inflamma@on.
A HEALTHY EPITHELIUM OFFERS PROTECTION AGAINST INFECTION
• Epithelium as a passive physical barrier
o Mul@layered vs single-layered Biological factors that reduce risk of HIV transmission
o Kera@nized vs non-kera@nized
o Protec@ve and immobilizing mucus
o Acidic vaginal pH
• Epithelium as an ac@ve front line of the immune system
o Innate defenses via Toll-like receptors
§ Defensins & an@microbial pep@des
§ Secretory leukocyte protease inhibitor (SLPI)
§ Lactoferrin, Lysozyme
§ Surfactant protein A
§ Complement
o Langerhans’ cells, @ssue-resident macrophages, recruitment of DC, T-cells
WHEN THINGS TURN BAD…
The innate and inflammatory responses directed against HIV can also enhance transmission. Because of the influx of
large numbers of HIV target cells (DC, MF, CD4+ Tcells…) driven by the inflammatory environment, there can be an
expansion of infec@on via cell-cell contacts.
STIs result in a thinned or damaged epithelium, providing direct access to target cells in the submucosal @ssue. This
results in a local inflammatory environment, which a6racts addi@onal immune/HIV target cells.
Bacterial vaginosis is a disbalanced environment of the vaginal Biological factors that increase risk of HIV transmission
microflora (lactobacilli). This causes a change in the normally acidic pH,
which normally has a protec@ve effect. It is also an increased risk for STI
acquisi@on.
3
, Pathogenesis and clinical aspects of tropical infec2ous diseases 2024-2025
HIV DISEASE COURSE
People transmit the virus when they have the highest viral loads. The virus keeps replica6ng and you build up a viral load in the body, but also in the genital
secre6ons. This occurs mostly during the early phase when they are not really aware they have HIV. Then, when they no6ce they have HIV, they suppress the
viral load in treatment. In cases of untreated pa6ents, there is of course more risk of transmission. (seen on page 2)
At first, people don’t know they are infected (eclipse phase).
HIV establishes the viral reservoir already, amer which remains
there for life. Amer ± 3 weeks, the virus can be detected in the
blood for the first @me and some symptoms arise. This is the
acute phase. In the chronic phase, the viral setpoint is
established and chronic inflamma@on occurs. The set point can
be higher or lower, for more-fit viruses, immune dysfunc@on
and high levels of inflamma@on or poorly fit viruses, stronger
immune responses and low levels of inflamma@on
respec@vely. The infec@on slowly progresses to AIDS.
The symptoms generally occur 5-30 days amer exposure and have a median dura@on of 14 days. Symptoms can be:
• Fever, fa@gue, malaise, arthralgias, headache, nausea, vomi@ng, diarrhea
• Lymphadenopathy, pharyngi@s, rash, weight loss, mucocutaneous ulcera@ons, asep@c meningi@s
• Leukopenia, thrombocytopenia, elevated liver enzymes
Amer 6 weeks, the body can recover a bit. The immune system tries to get
control over the virus and the CD4+ Tcell counts begin to rise again.
However, the viral load increases again, quasispecies are built. The CD4+
Tcell count will decrease again over the years. AIDS is established when the
CD4+ Tcell count is <200 cells/µl, and then there is a high risk of other
infec@ons.
The HIV disease course is variable. The progression of HIV, and thus the chronic phase, usually takes several years.
However, there are some excep@ons:
• Rapid progressor: These people do not really have a clinical latency. They establish AIDS and die amer months
or only a few years.
• Non-progressor: These people never progress to the final AIDS stage.
o These people are very interes@ng, because they seem to control the virus in a natural way. It is not
understood how this happens so it is important to inves@gate.
o If we can understand the underlying mechanisms of the non-progressors, we might find solu@ons or
even a cure.
HIV is a len;virus (retrovirus) so it integrates itself in the host genome. Once the virus infects the cell, it will integrate a
gene@c copy into our own genome and once it is there, it stays there. This happens before people realise they are
infected, show symptoms or even get treated. Once a person is infected, they are infected for life. Current treatments
are unable to cure the infec@on (because the integra@on in the genome). There is an ac@ve viral replica@on throughout
the course of the disease. ~10 billion virus par@cles are produced every day when untreated. The major reservoirs of
the virus are outside of the blood compartment: lympho-re@cular @ssues, bone marrow, lymph nodes, spleen, GALT,
CNS, genital tract.
HIV profoundly affects the immune system and leads to…
• Opportunis;c infec;ons
o Mycobacterium tuberculosis (see lecture by Leen Rigouts)
o Candidiasis, cryptococcosis, histoplasmosis (fungi)
o CMV, HSV
• Neurological symptoms
o Confusion, headaches, changes in behavior and vision, balance and coordina@on
4
