Complications of HIV Infection: Complications of HIV Infection: Opportunistic Infections and Opportunistic Infections and

MalignanciesMalignancies

Rafael E. Campo, MDRafael E. Campo, MD

Slides courtesy of Luis A. Espinoza, MDSlides courtesy of Luis A. Espinoza, MD

Division of Infectious Diseases,Division of Infectious Diseases,

University of Miami Miller School of MedicineUniversity of Miami Miller School of Medicine

Organs of the immune system and the Organs of the immune system and the normal immune responsenormal immune response

Foreign antigens are ingested and Foreign antigens are ingested and processed by macrophagesprocessed by macrophages

Processed antigens are presented to Processed antigens are presented to helper T-lymphocytes that recruit B-helper T-lymphocytes that recruit B-lymphocyteslymphocytes

B-lymphocytes produce antibodiesB-lymphocytes produce antibodies Antibodies attach to the antigens on Antibodies attach to the antigens on

pathogens and recruit macrophages pathogens and recruit macrophages and other cells to destroy the and other cells to destroy the pathogenpathogen

Once the pathogen is eliminated, Once the pathogen is eliminated, suppressor T-cells shut down the suppressor T-cells shut down the immune responseimmune response

Effects of HIV infection on the immune Effects of HIV infection on the immune systemsystem

HIV infects helper T-cells (also known as CD4+ cells)HIV infects helper T-cells (also known as CD4+ cells) The infected CD4+ cells become “HIV factories”The infected CD4+ cells become “HIV factories” Infected CD4+ cells die because of HIV infection itself Infected CD4+ cells die because of HIV infection itself

and because of the immune response directed at and because of the immune response directed at destroying HIVdestroying HIV

After years of ongoing infection, immune exhaustion After years of ongoing infection, immune exhaustion leads to massive CD4+ cell depletion and the inability to leads to massive CD4+ cell depletion and the inability to fight off opportunistic infections and unusual fight off opportunistic infections and unusual malignanciesmalignancies

Patient #1Patient #1

24 y/o male24 y/o male Graduate student at UMGraduate student at UM In good health all his lifeIn good health all his life MSM; sexually active without protectionMSM; sexually active without protection Abruptly develops fever, chills, a reddish rash on Abruptly develops fever, chills, a reddish rash on

the skin, a very sore throat, swollen lymph nodes in the skin, a very sore throat, swollen lymph nodes in his neck, intense headache made worse by light, his neck, intense headache made worse by light, nausea and vomitingnausea and vomiting

What is wrong with Patient #1?What is wrong with Patient #1?

1.1. Acute mononucleosisAcute mononucleosis

2.2. Acute HIV retroviral syndromeAcute HIV retroviral syndrome

3.3. Acute strep throatAcute strep throat

4.4. All of the aboveAll of the above

5.5. None of the aboveNone of the above

Natural history of HIV infection and Natural history of HIV infection and its stagesits stages

Stage Duration CD4+ count Clinical manifestations

Acute infection A few weeks to a few months

May decrease <500 for a short time but

will recover

Acute retroviral syndrome

Clinical latency Up to 7-10 years* 200-500 Few if any symptoms (+/- adenopathies)

AIDS Beyond 7-10 years <200 Opportunistic infections, unusual

malignancies, profound wasting

In <5% of patients, latency may last for the remainder of their lives

Clinical manifestations of the acute Clinical manifestations of the acute retroviral syndromeretroviral syndrome

Occurs in 50-90% of Occurs in 50-90% of individuals infected with individuals infected with HIVHIV

Occurs 2-4 weeks after the Occurs 2-4 weeks after the infectioninfection

Typically, the process goes Typically, the process goes on for 2-4 weeks and is self-on for 2-4 weeks and is self-limitedlimited

Described as “the worst flu Described as “the worst flu ever”ever”

Common manifestationsCommon manifestations– Fever 80-90%Fever 80-90%– Fatigue 70-90%Fatigue 70-90%– Rash 40-80%Rash 40-80%– Headache 32-70%Headache 32-70%– Adenopathies 40-70%Adenopathies 40-70%– Pharyngitis 50-70%Pharyngitis 50-70%– Myalgias, arthralgias 50-Myalgias, arthralgias 50-

70%70%– Meningitis (25%)Meningitis (25%)

Clinical course for Patient #1Clinical course for Patient #1

He goes to Student HealthHe goes to Student Health Work up reveals acute HIV infectionWork up reveals acute HIV infection Referred to an Infectious Diseases specialist; Referred to an Infectious Diseases specialist;

what should be done next?what should be done next?1.1. Careful observationCareful observation

2.2. Prompt initiation of antiretroviral therapyPrompt initiation of antiretroviral therapy

When to Start ART:When to Start ART:Global Consensus and DiversityGlobal Consensus and Diversity

DHHS. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision April 8, 2015.Günthard HF, et al. JAMA. 2014;312:410-425.EACS. http://www.europeanaidsclinicalsociety.org. Revision November 2014.BHIVA. www.bhiva.org. Revision November 2013.WHO. http://www.who.int/publications/guidelines/hiv_aids/en/index.html. Revision June 2013.

AIDS orHIV-Related Symptoms <200 200-350 350-500 >500

United States DHHS (2015) Yes Yes Yes Yes Yes

IAS-USA (2014) Yes Yes Yes Yes Yes

British HIV Association (2013) Yes Yes Yes Consider Defer

European AIDS Clinical Society (2014)

Yes Yes Yes Consider Consider

WHO (2013) Yes Yes Yes Yes Defer

CD4 Count (cells/mm3)

START Study:Initiation of ART in Early START Study:Initiation of ART in Early Asymptomatic HIV InfectionAsymptomatic HIV Infection

Lundgren J, et al. 8th IAS Conference. Vancouver, 2015. Abstract MOSY0301.The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print].

Multicontinental Study (n=4685)HIV-positive adults

Treatment-naive

CD4 >500 cells/mm3

Randomization1:1 Immediate ART (n=2326)

Deferred ART (n=2359)(CD4 Declined to <350 cells/mm3 or AIDS-related event)

Primary outcome a composite outcome of 2 major components:• Any serious AIDS-related event

- Death from AIDS or any AIDS-defining event, Hodgkin’s lymphoma

• Any serious non–AIDS-related event - CVD (myocardial infarction, stroke, or coronary revascularization) or death from CVD, end-stage renal disease (initiation of dialysis or

renal transplantation) or death from renal disease, liver disease (decompensated liver disease) or death from liver disease, non–AIDS-defining cancer (except for basal-cell or squamous cell skin cancer) or death from cancer, and any death not attributable to AIDS

5//2015: DSMB recommends stopping trial:Deferred arm offered ART

START Study Outcomes:Composite Primary START Study Outcomes:Composite Primary Endpoint and its ComponentsEndpoint and its Components

Immediate ART was superior to deferral Immediate ART was superior to deferral of ARTof ART

– Both for serious and non-serious AIDS Both for serious and non-serious AIDS eventsevents

Majority (68%) of the primary endpoints Majority (68%) of the primary endpoints occurred in patients with a CD4 >500 occurred in patients with a CD4 >500 cells/mmcells/mm33

Similar significant reductions were Similar significant reductions were noted across all patient subgroups noted across all patient subgroups

No increase in adverse events associated No increase in adverse events associated with immediate versus deferred ARTwith immediate versus deferred ART

Mean CD4 count in immediate ART arm Mean CD4 count in immediate ART arm was 194 cells/mmwas 194 cells/mm33 higher versus deferred higher versus deferred ART armART arm

Lundgren J, et al. 8th IAS Conference. Vancouver, 2015. Abstract MOSY0301.The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print].

Nu

mb

er o

f E

ven

ts

AIDS-Related

Non-AIDS Related

Components(Serious Events)

CompositeEndpoint

96Deferred ART (n=2359)

Immediate ART (n=2326)

42

50

14

47

29

Number of Serious Events

57%Reduction(P<0.001)

72%Reduction(P<0.001)

39%Reduction(P=0.04)

At what CD4+ count should antiretroviral therapy At what CD4+ count should antiretroviral therapy optimally be started in HIV infected individuals?optimally be started in HIV infected individuals?

1.1. <200<200

2.2. <350<350

3.3. <500<500

4.4. >500>500

Common manifestations of advanced Common manifestations of advanced HIV infection/AIDS by organ system HIV infection/AIDS by organ system Pulmonary diseasesPulmonary diseases

– Pneumocystis pneumoniaPneumocystis pneumonia

– TuberculosisTuberculosis

– Pneumococcal pneumoniaPneumococcal pneumonia

Central nervous systemCentral nervous system– ToxoplasmosisToxoplasmosis

– CryptococcosisCryptococcosis

– CytomegalovirusCytomegalovirus

EyesEyes– CytomegalovirusCytomegalovirus

Disseminated diseasesDisseminated diseases– Mycobacterium avium Mycobacterium avium

intracellulareintracellulare

– Bacterial infections (e.g. Bacterial infections (e.g. salmonellosis)salmonellosis)

SkinSkin– CandidiasisCandidiasis

– Kaposi’s sarcomaKaposi’s sarcoma

Immune systemImmune system– Non-Hodgkin’s lymphomaNon-Hodgkin’s lymphoma

Gastrointestinal diseasesGastrointestinal diseases

Common manifestations of advanced Common manifestations of advanced HIV infection/AIDS by pathogenHIV infection/AIDS by pathogen

Fungal diseasesFungal diseases– Pneumocystis pneumoniaPneumocystis pneumonia– Oral and esophageal candidiasisOral and esophageal candidiasis– CryptococcosisCryptococcosis– Other endemic mycoses: Other endemic mycoses:

histoplasmosis, histoplasmosis, coccidiodomycosiscoccidiodomycosis

Mycobacterial diseasesMycobacterial diseases– Mycobacterium tuberculosisMycobacterium tuberculosis– Mycobacterium avium Mycobacterium avium

intracellulareintracellulare– CytomegalovirusCytomegalovirus

Protozoal diseasesProtozoal diseases– ToxoplasmosisToxoplasmosis

– Various gastrointestinal Various gastrointestinal pathogenspathogens

Viral diseasesViral diseases– CytomegalovirusCytomegalovirus

– Epstein-Barr virusEpstein-Barr virus

– Human herpes virus 8Human herpes virus 8

Bacterial diseasesBacterial diseases– Streptococcus pneumoniaeStreptococcus pneumoniae

– Salmonellosis Salmonellosis

Pneumocystis Pneumonia (PCP)Pneumocystis Pneumonia (PCP)

Pneumocystis jiroveciPneumocystis jiroveci : Fungus: Fungus Most common siteMost common site : Lungs: Lungs Other sitesOther sites : Retina, skin, liver, bone marrow,: Retina, skin, liver, bone marrow,

and lymph nodes and lymph nodes Signs and symptomsSigns and symptoms DiagnosisDiagnosis

Pneumocystis PneumoniaPneumocystis Pneumonia

CD4 count threshold:CD4 count threshold: - 200 cell per uL or < 14%- 200 cell per uL or < 14%

- Oral thrush, HSV, weight loss- Oral thrush, HSV, weight loss Recomm ProphylaxisRecomm Prophylaxis - TMP/SMX (160/800)- TMP/SMX (160/800) Alternative agents:Alternative agents: - Dapsone +/- Pyrimethamine + - Dapsone +/- Pyrimethamine +

folinic acid folinic acid

- Atovaquone- Atovaquone

- Aerosolized Pentamidine- Aerosolized Pentamidine

Pneumocystis PneumoniaPneumocystis Pneumonia

TherapyTherapy::

- TMP/SMX +/- Corticosteroids- TMP/SMX +/- Corticosteroids

- Pentamidine- Pentamidine

- Atovaquone- Atovaquone

- Clindamycin + Primaquine- Clindamycin + Primaquine

- Dapsone + TMP- Dapsone + TMP

Toxoplasmosis (I)Toxoplasmosis (I)

Toxoplasma gondiiToxoplasma gondii Carried by cats, birds and other domesticated animals; Carried by cats, birds and other domesticated animals;

soil contaminated by cat feces, and in meatsoil contaminated by cat feces, and in meat Most common site is the brainMost common site is the brain It can infect lungs, retina of the eyes, heart, pancreas, It can infect lungs, retina of the eyes, heart, pancreas,

liver, colon and testesliver, colon and testes SymptomsSymptoms DiagnosisDiagnosis

Toxoplasmosis (II)Toxoplasmosis (II)

CD4 count threshold:CD4 count threshold: - Usually < 100 per uL.- Usually < 100 per uL.

- With (+) antitoxoplasma IgG.- With (+) antitoxoplasma IgG. Recomm prophylaxisRecomm prophylaxis - TMP/SMX (160/800)- TMP/SMX (160/800) Alternative agents:Alternative agents: - TMP/SMX (80/400)- TMP/SMX (80/400)

- Dapsone + Pyrimethamine +- Dapsone + Pyrimethamine +

folinic acidfolinic acid

- Atovaquone- Atovaquone

Toxoplasmosis (III)Toxoplasmosis (III)

TherapyTherapy::

Sulfadiazine + Pyrimethamine + Folinic acidSulfadiazine + Pyrimethamine + Folinic acid Clindamycin + Pyrimethamine + Folinic acidClindamycin + Pyrimethamine + Folinic acid Atovaquone + Pyrimethamine + Folinic acidAtovaquone + Pyrimethamine + Folinic acid Azithromycin + Pyrimethamine + Folinic acidAzithromycin + Pyrimethamine + Folinic acid Atovaquone + SulfadiazineAtovaquone + Sulfadiazine

Mycobacterium avium (I)Mycobacterium avium (I)

Mycobacterium aviumMycobacterium avium complex and immunosupression complex and immunosupression Sources are food, water, and soilSources are food, water, and soil Localized or disseminated infectionLocalized or disseminated infection Symptoms of fever, weight loss, night sweats, fatigue, Symptoms of fever, weight loss, night sweats, fatigue,

anemia, loss of appetite, loose stools or diarrhea, anemia, loss of appetite, loose stools or diarrhea, abdominal pain, enlarged liver or spleenabdominal pain, enlarged liver or spleen

DiagnosisDiagnosis

Mycobacterium avium (II)Mycobacterium avium (II)

CD4 count thresholdCD4 count threshold - 50 cells per uL.- 50 cells per uL. Recomm. prophylaxisRecomm. prophylaxis - Azithromycin- Azithromycin

- Clarithromycin- Clarithromycin Alternative agentsAlternative agents - Rifabutin- Rifabutin

- Azithromycin + Rifabutin- Azithromycin + Rifabutin

Mycobacterium Avium (III)Mycobacterium Avium (III)

TherapyTherapy::

Clarithromycin + Ethambutol +/- RifabutinClarithromycin + Ethambutol +/- Rifabutin Azithromycin + Ethambutol +/- RifabutinAzithromycin + Ethambutol +/- Rifabutin Alternatives as second line drugs: Ciprofloxacine,Alternatives as second line drugs: Ciprofloxacine,

Ofloxacine, Amikacin, Kanamycin.Ofloxacine, Amikacin, Kanamycin.

Mycobacterium Tuberculosis (I)Mycobacterium Tuberculosis (I)

CD4 count threshold:CD4 count threshold: - Any, for TST (+) - Any, for TST (+) > > 5 mm5 mm

- Anergic but with high risk- Anergic but with high risk

- Known exposure to active - Known exposure to active contagious case contagious case

Recomm prophylaxisRecomm prophylaxis - INH + Vitamin B6- INH + Vitamin B6

- Rifampin or Rifabutin- Rifampin or Rifabutin Alternative agents:Alternative agents: - Rifampin + Pyrazinamide- Rifampin + Pyrazinamide MDR Tuberculosis*:MDR Tuberculosis*: - Rifampin or Rifabutin + - Rifampin or Rifabutin +

Pyrazinamide Pyrazinamide

Mycobacterium Tuberculosis (II)Mycobacterium Tuberculosis (II)

TherapyTherapy::

First line drugs:First line drugs: Second line drugs:Second line drugs:- Isoniazid- Isoniazid - Ethionamide- Ethionamide- Rifampin- Rifampin - Ofloxacin, Ciprofloxacin- Ofloxacin, Ciprofloxacin- Ethambutol- Ethambutol - Streptomycin- Streptomycin- Pyrazinamide- Pyrazinamide - Cycloserine- Cycloserine

- Capreomycin- Capreomycin- Kanamycin- Kanamycin

Cytomegalovirus (I)Cytomegalovirus (I)

HerpesvirusHerpesvirus - Mucous-membrane contact.- Mucous-membrane contact.

- Tissue transplant.- Tissue transplant.

- Blood transfusion.- Blood transfusion. May affect retina, colon, esophagus; lungs, brain, heart, May affect retina, colon, esophagus; lungs, brain, heart,

thymus, pancreas, larynx, thyroid, adrenal glands, liver, thymus, pancreas, larynx, thyroid, adrenal glands, liver, and gallbladder.and gallbladder.

SymptomsSymptoms DiagnosisDiagnosis

Cytomegalovirus (II)Cytomegalovirus (II)

CD4 count threshold: - 50 cell per uLCD4 count threshold: - 50 cell per uL

- 100 cells per uL if prior - 100 cells per uL if prior OIOI

- CMV antibody positivity- CMV antibody positivity Recomm Prophylaxis - Ophthalmologic evaluationRecomm Prophylaxis - Ophthalmologic evaluation

- Oral ganciclovir- Oral ganciclovir

Multifocal CMV Retinitis

Syntex Lab

Multifocal CMV Retinitis

Syntex Lab

Cytomegalovirus (III)Cytomegalovirus (III)

TherapyTherapy::

Ganciclovir PO or IV or intraocularGanciclovir PO or IV or intraocular Valganciclovir (oral)Valganciclovir (oral) Foscarnet IV Foscarnet IV Cidofovir IV + ProbenecidCidofovir IV + Probenecid

KaposiKaposi’’s Sarcomas Sarcoma

Human Herpesvirus-8 (HHV-8 or KSHV)Human Herpesvirus-8 (HHV-8 or KSHV) Malignancy versus angiogenic disorderMalignancy versus angiogenic disorder Detected in tissue of KS lesions, in semen and peripheral Detected in tissue of KS lesions, in semen and peripheral

blood monocytesblood monocytes Signs and symptomsSigns and symptoms DiagnosisDiagnosis

From: Atlas o HIV DIseaseFrom: Atlas o HIV DIsease

f

KaposiKaposi’’s Sarcomas Sarcoma

TherapyTherapy:: AntiretroviralsAntiretrovirals Local excision, liquid nitrogen, radiation therapy.Local excision, liquid nitrogen, radiation therapy. Intralesional therapy (sotradecol, vinblastine, alitretinoin)Intralesional therapy (sotradecol, vinblastine, alitretinoin) -Interferon-Interferon Chemotherapy: Doxorubicin + Bleo + VincristineChemotherapy: Doxorubicin + Bleo + Vincristine

- Etoposide, Paclitaxel (Taxol)- Etoposide, Paclitaxel (Taxol)

- Liposomal Doxorubicin and Daunorubicin- Liposomal Doxorubicin and Daunorubicin

Fungal InfectionsFungal Infections

CD4 count threshold:CD4 count threshold: - No determined.- No determined.

- Usually < 100 per uL.- Usually < 100 per uL. Recomm ProphylaxisRecomm Prophylaxis - ? Fluconazole- ? Fluconazole Alternative agents:Alternative agents: - ? Ketoconazole- ? Ketoconazole

- ? Clotrimazole- ? Clotrimazole

- ? Itraconazole- ? Itraconazole

Cryptococcal InfectionsCryptococcal Infections

Cryptococcus neoformansCryptococcus neoformans Areas heavily contaminated with bird excrement.Areas heavily contaminated with bird excrement. Infects meninges, skin and lungsInfects meninges, skin and lungs Signs and symptomsSigns and symptoms Diagnosis and prognosisDiagnosis and prognosis Therapy: Therapy: - Amphotericin-B +/- Flucytosine- Amphotericin-B +/- Flucytosine

- Fluconazole +/- Flucytosine- Fluconazole +/- Flucytosine

- Itraconazole- Itraconazole

HIV-Related CandidiasisHIV-Related Candidiasis

Candida albicans, Candida parapsilosis, Candida krusei, Candida albicans, Candida parapsilosis, Candida krusei, Candida tropicalis, Candida glabrataCandida tropicalis, Candida glabrata..

Skin and mucous membranesSkin and mucous membranes Signs and symptomsSigns and symptoms DiagnosisDiagnosis Therapy:Therapy: - Clotrimazole, Nystatin, Ketoconazole- Clotrimazole, Nystatin, Ketoconazole

- Fluconazole, Itraconazole- Fluconazole, Itraconazole- Amphotericin-B- Amphotericin-B- Caspofungin- Caspofungin

Other Fungal InfectionsOther Fungal Infections

HistoplasmosisHistoplasmosis: Lungs, skin, GI system.: Lungs, skin, GI system.

Itraconazole, Fluconazole.Itraconazole, Fluconazole. AspergillosisAspergillosis:: Lungs and sinuses.Lungs and sinuses.

Extrapulmonary dissemination.Extrapulmonary dissemination.

Amphotericin-B, Itraconazole, CaspofunginAmphotericin-B, Itraconazole, Caspofungin CoccidiomycosisCoccidiomycosis: Lungs, kidneys, spleen, lymph : Lungs, kidneys, spleen, lymph

nodes, brain, thyroid gland. nodes, brain, thyroid gland.

Itraconazole, Fluconazole.Itraconazole, Fluconazole.

Bacterial InfectionsBacterial Infections

Salmonellosis :Salmonellosis : Systemic and disseminated.Systemic and disseminated. Pneumonia : Pneumonia : Streptococcus pneumonia.Streptococcus pneumonia.

Haemophilus influenzaHaemophilus influenza.. EnteritisEnteritis : : Shigella, Campylobacter.Shigella, Campylobacter. SinusitisSinusitis : : Staphylococcus epidermidis.Staphylococcus epidermidis.

Pseudomona aeruginosaPseudomona aeruginosa.. Syphilis/Neurosyphilis.Syphilis/Neurosyphilis. Bacillary angiomatosis: Bacillary angiomatosis: Bartonella henselaeBartonella henselae.. Nocardiosis.Nocardiosis.

Viral InfectionsViral Infections

Hepatitis: HAV, HBV, HCV, HDV, HGV.Hepatitis: HAV, HBV, HCV, HDV, HGV. Herpes simplex virus: HSV-1, HSV-2.Herpes simplex virus: HSV-1, HSV-2. Herpes zoster virus.Herpes zoster virus. Human Papilloma Virus.Human Papilloma Virus. Molluscum Contagiosum.Molluscum Contagiosum. Oral Hairy Leukoplaquia.Oral Hairy Leukoplaquia. Progressive Multifocal Leukoencephalopathy.Progressive Multifocal Leukoencephalopathy.

HSV EsophagitisHSV Esophagitis

Protozoal InfectionsProtozoal Infections

Cryptosporidiosis: Cryptosporidiosis: Cryptosporidium parvumCryptosporidium parvum

Food or water contaminated by fecal material.Food or water contaminated by fecal material.

Paromomycin, Clarithromycin, Azithromycin.Paromomycin, Clarithromycin, Azithromycin. Isosporiasis: Isosporiasis: Isospora belliIsospora belli..

Cotrimoxazole, Pyrimethamine + Leucovorin.Cotrimoxazole, Pyrimethamine + Leucovorin. Microsporidiosis: Microsporidiosis: Enterocytozoon bieneusi, Enterocytozoon bieneusi,

Encephalitozoon hellen, Encephalitozoon cuniculi, Septata Encephalitozoon hellen, Encephalitozoon cuniculi, Septata intestinalis.intestinalis.

Albendazole, Metronidazole, Thalidomide.Albendazole, Metronidazole, Thalidomide.

Other DisordersOther Disorders

ThrombocytopeniaThrombocytopenia Diarrhea and malabsortionDiarrhea and malabsortion Wasting syndromeWasting syndrome Aphthous ulcersAphthous ulcers Peripheral neuropathyPeripheral neuropathy Dementia syndromeDementia syndrome MalignanciesMalignancies Progressive multifocal leucoencephalopathyProgressive multifocal leucoencephalopathy

All of the following are pulmonary All of the following are pulmonary conditions associated with AIDS except:conditions associated with AIDS except:

1.1. Pneumocystis pneumoniaPneumocystis pneumonia

2.2. TuberculosisTuberculosis

3.3. AsthmaAsthma

4.4. Pneumococcal pneumoniaPneumococcal pneumonia

All of the following are central nervous system All of the following are central nervous system conditions associated with AIDS exceptconditions associated with AIDS except

1.1. Alzheimer’s diseaseAlzheimer’s disease

2.2. Toxoplasma encephalitisToxoplasma encephalitis

3.3. Cryptococcal meningitisCryptococcal meningitis

4.4. AIDS-associated dementiaAIDS-associated dementia

All of the following are viral infections All of the following are viral infections commonly seen in AIDS patients except:commonly seen in AIDS patients except:

1.1. Cytomegalovirus retinitsCytomegalovirus retinits

2.2. Human herpes virus 8-associated Kaposi’s Human herpes virus 8-associated Kaposi’s sarcomasarcoma

3.3. Dengue feverDengue fever

4.4. Human papillomavirus-associated genital Human papillomavirus-associated genital condylomascondylomas

Patients on antiretroviral therapy Patients on antiretroviral therapy (ART)(ART)

Modern ART successfully suppresses viral Modern ART successfully suppresses viral replication and leads to gradual restoration of replication and leads to gradual restoration of CD4+ cell counts in >90% of patientsCD4+ cell counts in >90% of patients

However, there is ongoing systemic inflammation However, there is ongoing systemic inflammation and these patients are not immunologically and these patients are not immunologically normalnormal

Many organ systems are aging prematurelyMany organ systems are aging prematurely

Systems affected by ongoing inflammation and Systems affected by ongoing inflammation and premature aging in patients on successful ARTpremature aging in patients on successful ART

Cardiovascular: heart attacks, strokesCardiovascular: heart attacks, strokes Central nervous system: neurocognitive impairmentCentral nervous system: neurocognitive impairment Metabolic: diabetes and glucose intolerance, abnormal Metabolic: diabetes and glucose intolerance, abnormal

lipid levels, abnormal fat distribution (lipodystrophy)lipid levels, abnormal fat distribution (lipodystrophy) Bones: osteoporosis and premature fracturesBones: osteoporosis and premature fractures Renal: impaired kidney functionRenal: impaired kidney function Hepatic: greatly accelerated progression of chronic Hepatic: greatly accelerated progression of chronic

hepatitis B and Chepatitis B and C

Among patients successfully treated with Among patients successfully treated with antiretroviral agents with complete viral antiretroviral agents with complete viral suppression, there is no more systemic suppression, there is no more systemic

inflammation and the aging process is normal inflammation and the aging process is normal

1.1. TrueTrue

2.2. FalseFalse