HIV-associated opportunistic infections of the CNS

doi:10.1016/S1474-4422(12)70098-4

The Lancet Neurology

Volume 11, Issue 7, July 2012, Pages 605-617

https://doi.org/10.1016/S1474-4422(12)70098-4 Get rights and content

Summary

Survival in people infected with HIV has improved because of an increasingly powerful array of antiretroviral treatments, but neurological symptoms due to comorbid conditions, including infection with hepatitis C virus, malnutrition, and the effects of accelerated cardiovascular disease and ageing, are increasingly salient. A therapeutic gap seems to exist between the salutary effects of antiretroviral regimens and the normalisation of neurological function in HIV-associated neurocognitive disorders. Despite the advances in antiretroviral therapy, CNS opportunistic infections remain a serious burden worldwide. Most opportunistic infections can be recognised by a combination of characteristic clinical and radiological features and are treatable, but some important challenges remain in the diagnosis and management of HIV-associated opportunistic infections.

Introduction

HIV infection leads to substantial morbidity and mortality worldwide. In 2009, 33·3 million adults and children were living with HIV, two-thirds of whom were in sub-Saharan Africa.

Overall, the annual incidence of new infections has declined by 19% since the peak of the worldwide HIV epidemic in 1999, in line with the Millennium Development Goal. Nevertheless, about 2·6 million individuals were newly infected in 2009, and the incidence continues to increase in some regions.¹ 7000 new HIV infections occur daily, 95% of which are in low-income and middle-income countries, where only about a third of patients who require antiretroviral drugs have access to them.¹

In high-income countries, the introduction of combination antiretroviral therapy (cART) in 1996 greatly changed the incidence of neurological opportunistic infections, from 13·1 per 1000 patient-years in 1996–97 to 1·0 per 1000 in 2006–07 (Table 1, Table 2).2, 7 Many of the opportunistic infections that affect the CNS are AIDS-defining conditions, including progressive multifocal leukoencephalopathy (PML), CNS cytomegalovirus, CNS tuberculosis, cryptococcal meningitis, and cerebral toxoplasmosis, including toxoplasmic encephalitis (table 2), and all have high associated mortality.⁸ Treatment of CNS opportunistic infections in conjunction with cART improves survival, but such infections continue to be important, especially where access to cART is limited.

In this Review we focus on the most common CNS opportunistic infections associated with HIV infection worldwide, and provide a summary of each in terms of epidemiology, clinical presentations, diagnosis, and treatment.

Section snippets

Biology of HIV-1

HIV-1 infection accounts for most of the global HIV pandemic. Only 1–2 million of the 33 million HIV infections are caused by HIV-2. HIV-1 belongs to the family Retroviridae and genus Lentivirus.⁹ It is a single-stranded, positive-sense RNA virus that contains a reverse transcriptase, which transcribes viral RNA into DNA that is integrated into the host's genome as a provirus. HIV-1 primarily targets CD4 receptors and infects CD4-positive T lymphocytes and cells of the monocyte or macrophage

Clinical features of CNS opportunistic infections

CNS opportunistic infections should be suspected in all people with advanced HIV infection. Individuals who are unaware of their HIV status can first present with CNS opportunistic infections. Additionally, in patients in whom cART is started, immune reconstitution inflammatory syndrome (IRIS) might unmask previously unsuspected CNS opportunistic infections. The main diagnostic features of CNS opportunistic infections are clinical presentation, temporal evolution, and CSF and radiographic

cART and management of CNS opportunistic infections

In patients with CNS opportunistic infections, the timing of cART initiation is pertinent to the management of treatment-naive patients as well as those who have previously received cART. The use of cART to achieve immune restoration is especially effective in patients with opportunistic infections for which no effective antimicrobial therapy is available, including PML, but several complications are of concern, including drug interactions, toxic effects, and IRIS.

CNS opportunistic infections

Tuberculous meningitis and brain abscesses

WHO estimates that a third of the world's population is infected with Mycobacterium tuberculosis and that individuals with HIV co-infection are at increased risk of disseminated, active forms of disease, including tuberculous meningitis.⁴² The exact incidence of HIV-associated tuberculous meningitis is uncertain because epidemiological data are limited, especially for areas where co-infection rates are highest, such as sub-Saharan Africa.⁴²

Infection with M tuberculosis occurs after inhalation

Toxoplasmic encephalitis

Toxoplasmic encephalitis remains the most commonly reported neurological opportunistic infection since cART was introduced, although declines in incidence have been seen: in 2007, the incidence in the UK was 0·4 per 1000 person-years, which was a notable decline from 3·2 only 10 years earlier.⁷ Because toxoplasmic encephalitis is caused by reactivation of encysted bradyzoites rather than primary infection, rates vary according to the seroprevalence of Toxoplasma gondii in the population. Risk

Cryptococcal meningitis

Before the introduction of cART, 5–10% of patients with AIDS developed cryptococcal meningitis. Although the incidence has fallen, this disease remains a major concern in sub-Saharan Africa and south and southeast Asia.⁶³

Cryptococcus neoformans is an encapsulated yeast commonly found in soil and in excrement from pigeons. Cryptococcus gattii is generally found in tropical and subtropical regions, and causes disease in immunocompetent individuals.⁶⁴ Exposure to Cryptococcus spp probably occurs

Cytomegalovirus encephalitis

Neurological diseases caused by cytomegalovirus are rare but very serious. Infection can lead to encephalitis, retinitis, radiculomyelitis, or mononeuritis multiplex. Although cytomegalovirus encephalitis seems to occur at similar rates worldwide, retinitis has a distinct geographical distribution—it is the predominant HIV-associated eye disease in Asia, where up to a third of HIV-infected patients are affected. ⁷⁸

The ubiquitous herpes virus, cytomegalovirus is endemic worldwide and usually

Progressive multifocal leukoencephalopathy

PML is a rare but severe CNS opportunistic infection that is caused by the reactivation of latent JC virus, a polyomavirus, in immunosuppressed individuals. Unlike most of the other HIV-associated CNS opportunistic infections, which are very rare when the CD4-cell count is higher than 100–200 cells per μL, PML occasionally occurs in patients with much higher CD4-cell counts (table 3).89, 90 The seroprevalence of JC virus in the general population is 50–90%,91, 92, 93 and about 30% of people

Primary CNS lymphoma

HIV infection is a well-established risk factor for primary CNS lymphoma.¹²³ Since cART was introduced, the incidence among people with HIV infection has substantially declined,¹²⁴ and it is now a rare disease. Between 2001 and 2007 in the USA, around 26 new cases of primary CNS lymphoma per 100 000 person-years were reported among people with AIDS compared with 0·38 cases among people without AIDS.¹²⁵

Primary CNS lyphoma must be distinguished from secondary involvement of the CNS in systemic

Herpes simplex virus encephalitis

Herpes simplex virus is an infrequent cause of CNS opportunistic infections. In studies from before and after the widespread use of cART, PCR detection in CSF of DNA for herpes simplex virus type 1 or 2 was only 2%,135, 136 whereas detection of cytomegalovirus was 74% in adults with HIV infection and neurological symptoms.³⁵ Co-infection of herpes simplex virus 2 and Epstein-Barr virus has been reported.¹³⁶

Herpes simplex virus is a neurotropic virus. Type 1 is commonly acquired in early life

Conclusions

Although CNS opportunistic infections are decreasing in frequency, they continue to have a devastating effect on HIV-positive individuals, especially those in whom diagnosis is delayed or HIV treatment is inadequate. Mortality is often high even with appropriate treatment, and recurrences and residual neurological deficits are common. For some disorders, such as PML, primary CNS lymphoma, and multidrug-resistant tuberculosis, curative treatments are not yet available, which underscores the

Search strategy and selection criteria

We chose the infections to include in this Review on the basis of the frequency and importance of the infection in the CNS in people infected with HIV. References were found by searches of PubMed for papers published from January, 1990, to February, 2012. We used the search term “human immunodeficiency virus” AND “primary central nervous system lymphoma” OR “Epstein Barr virus” OR “JC virus” OR “progressive multifocal leukoencephalopathy” OR “tuberculosis” OR “toxoplasmosis” OR

References (138)

D Eza et al.
Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru
Pathol Res Pract
(2006)
H Choe et al.
The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates
Cell
(1996)
SM Katrak et al.
The clinical, radiological and pathological profile of tuberculous meningitis in patients with and without human immunodeficiency virus infection
J Neurol Sci
(2000)
RL Skolasky et al.
HIV-associated primary CNS lymorbidity and utility of brain biopsy
J Neurol Sci
(1999)
S Marais et al.
Tuberculous meningitis: a uniform case definition for use in clinical research
Lancet Infect Dis
(2010)
CS Meira et al.
Immunodiagnosis in cerebrospinal fluid of cerebral toxoplasmosis and HIV-infected patients using Toxoplasma gondii excreted/secreted antigens
Diagn Microbiol Infect Dis
(2011)
DJ Skiest et al.
SPECT thallium-201 combined with Toxoplasma serology for the presumptive diagnosis of focal central nervous system mass lesions in patients with AIDS
J Infect
(2000)
I Wijewardana et al.
Large volume lumbar punctures in cryptococcal meningitis clear cryptococcal antigen as well as lowering pressure
J Infect
(2011)
KF Macsween et al.
Lumbar drainage for control of raised cerebrospinal fluid pressure in cryptococcal meningitis: case report and review
J Infect
(2005)
R Parkes-Ratanshi et al.
Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial
Lancet Infect Dis
(2011)

KK Biron

Antiviral drugs for cytomegalovirus diseases

Antiviral Res

(2006)

RR Razonable

Antiviral drugs for viruses other than human immunodeficiency virus

Mayo Clin Proc

(2011)

JT Holbrook et al.

Evaluation of the United States public health service guidelines for discontinuation of anticytomegalovirus therapy after immune recovery in patients with cytomegalovirus retinitis

Am J Ophthalmol

(2011)

CC Posthuma et al.

Mass spectrometry-based comparative sequencing to detect ganciclovir resistance in the UL97 gene of human cytomegalovirus

J Clin Virol

(2011)

Global report: UNAIDS report on the global AIDS epidemic, 2010

(2010)

L Garvey et al.

HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era

Eur J Neurol

(2011)

EJ Wright et al.

NeuroAIDS in the Asia Pacific Region

J Neurovirol

(2008)

CB Holmes et al.

Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa

Clin Infect Dis

(2003)

JE Kaplan et al.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America

MMWR Recomm Rep

(2009)

A d’Arminio Monforte et al.

Changing incidence of central nervous system diseases in the EuroSIDA cohort

Ann Neurol

(2004)

AJ Mocroft et al.

Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group

Int J Epidemiol

(1997)

IM Chiu et al.

Nucleotide sequence evidence for relationship of AIDS retrovirus to lentiviruses

Nature

(1985)

T Dragic et al.

HIV-1 entry into CD4⁺ cells is mediated by the chemokine receptor CC-CKR-5

Nature

(1996)

GW Rutherford et al.

Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11 year follow up study

BMJ

(1990)

AS Fauci et al.

Immunopathogenic mechanisms of HIV infection

Ann Intern Med

(1996)

ES Daar et al.

Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection

N Engl J Med

(1991)

JM Brenchley et al.

HIV disease: fallout from a mucosal catastrophe?

Nat Immunol

(2006)

RA Koup et al.

Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome

J Virol

(1994)

JT Safrit et al.

Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope

J Exp Med

(1994)

D Finzi et al.

Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy

Science

(1997)

SJ Clark et al.

High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection

N Engl J Med

(1991)

RE Rothman et al.

A decision guideline for emergency department utilization of noncontrast head computed tomography in HIV-infected patients

Acad Emerg Med

(1999)

A Antinori et al.

Prevalence, associated factors, and prognostic determinants of AIDS-related toxoplasmic encephalitis in the era of advanced highly active antiretroviral therapy

Clin Infect Dis

(2004)

VL Pereira-Chioccola et al.

Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients

Future Microbiol

(2009)

JR Berger et al.

Progressive multifocal leukoencephalopathy in patients with HIV infection

J Neurovirol

(1998)

FN Engsig et al.

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

J Infect Dis

(2009)

IS Haldorsen et al.

AIDS-related primary central nervous system lymphoma: a Norwegian national survey 1989–2003

BMC Cancer

(2008)

S Bayraktar et al.

Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors

J Neurooncol

(2011)

BM Anduze-Faris et al.

Induction and maintenance therapy of cytomegalovirus central nervous system infection in HIV-infected patients

AIDS

(2000)

NR Holland et al.

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS)

Neurology

(1994)

JR Graybill et al.

Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups

Clin Infect Dis

(2000)

CM van der Horst et al.

Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group

N Engl J Med

(1997)

S Antinori et al.

The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis

J Clin Microbiol

(2005)

ME Torok et al.

Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-associated tuberculous meningitis

Clin Infect Dis

(2011)

GE Thwaites et al.

The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with tuberculous meningitis

J Infect Dis

(2005)

KL Tyler

Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's

Herpes

(2004)

A Antinori et al.

Diagnosis of AIDS-related focal brain lesions: a decision-making analysis based on clinical and neuroradiologic characteristics combined with polymerase chain reaction assays in CSF

Neurology

(1997)

VP Mathews et al.

AIDS-related CNS cryptococcosis: radiologic-pathologic correlation

AJNR Am J Neuroradiol

(1992)

Evaluation and management of intracranial mass lesions in AIDS. Report of the Quality Standards Subcommittee of the American Academy of Neurology

Neurology

(1998)

RM Levy et al.

MRI-guided stereotaxic brain biopsy in neurologically symptomatic AIDS patients

J Acquir Immune Defic Syndr

(1991)

Cited by (124)

European society of Clinical Microbiology and Infectious Diseases guidelines on diagnosis and treatment of brain abscess in children and adults
2024, Clinical Microbiology and Infection
These European Society of Clinical Microbiology and Infectious Diseases guidelines are intended for clinicians involved in diagnosis and treatment of brain abscess in children and adults.
Key questions were developed, and a systematic review was carried out of all studies published since 1 January 1996, using the search terms ‘brain abscess’ OR ‘cerebral abscess’ as Mesh terms or text in electronic databases of PubMed, Embase, and the Cochrane registry. The search was updated on 29 September 2022. Exclusion criteria were a sample size <10 patients or publication in non-English language. Extracted data was summarized as narrative reviews and tables. Meta-analysis was carried out using a random effects model and heterogeneity was examined by I² tests as well as funnel and Galbraith plots. Risk of bias was assessed using Risk Of Bias in Non-randomised Studies - of Interventions (ROBINS-I) (observational studies) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (diagnostic studies). The Grading of Recommendations Assessment, Development and Evaluation approach was applied to classify strength of recommendations (strong or conditional) and quality of evidence (high, moderate, low, or very low).
Magnetic resonance imaging is recommended for diagnosis of brain abscess (strong and high). Antimicrobials may be withheld until aspiration or excision of brain abscess in patients without severe disease if neurosurgery can be carried out within reasonable time, preferably within 24 hours (conditional and low). Molecular-based diagnostics are recommended, if available, in patients with negative cultures (conditional and moderate). Aspiration or excision of brain abscess is recommended whenever feasible, except for cases with toxoplasmosis (strong and low). Recommended empirical antimicrobial treatment for community-acquired brain abscess in immuno-competent individuals is a 3rd-generation cephalosporin and metronidazole (strong and moderate) with the addition of trimethoprim-sulfamethoxazole and voriconazole in patients with severe immuno-compromise (conditional and low). Recommended empirical treatment of post-neurosurgical brain abscess is a carbapenem combined with vancomycin or linezolid (conditional and low). The recommended duration of antimicrobial treatment is 6–8 weeks (conditional and low). No recommendation is offered for early transition to oral antimicrobials because of a lack of data, and oral consolidation treatment after ≥6 weeks of intravenous antimicrobials is not routinely recommended (conditional and very low). Adjunctive glucocorticoid treatment is recommended for treatment of severe symptoms because of perifocal oedema or impending herniation (strong and low). Primary prophylaxis with antiepileptics is not recommended (conditional and very low). Research needs are addressed.
Human Immunodeficiency Virus: Opportunistic Infections and Beyond
2023, Neuroimaging Clinics of North America
Citation Excerpt :
OIs typically result from reactivation of latent viral, fungal, or parasitic infection, and they most commonly occur when the CD4 cell count is 200 cells/mm3 or less, and, in up to 15% of HIV-infected patients, more than one OI can be present.2 Patients with severe immune suppression (CD4-cell count lower than 200 cells/mm3) are at risk of toxoplasma encephalitis, cryptococcal meningitis, cytomegalovirus (CMV) infection, primary CNS lymphoma, and PML, whereas patients with moderate immune suppression (CD4-cell counts of 200–500 cells/mm3) are at risk of tuberculous meningitis and PML.2 The incidence of OIs varies based on loco regional and socioeconomic differences and the relative availability of ART28; for example, in the United Kingdom, common OIs include toxoplasmosis, TB, PML, cryptococcal meningitis, CMV, and varicella zoster.
Characterizing the enemy: Opportunistic infections in the central nervous system in HIV patients, a Colombian case series
2022, Neurologia Argentina
Las infecciones oportunistas continúan siendo una de las principales causas de morbimortalidad en personas con VIH. Además, el sistema nervioso central es uno de los sistemas más frecuentemente comprometidos. A pesar de esto y la alta tasa de mortalidad por sida en Colombia, solo hay unos pocos estudios que caracterizan las infecciones oportunistas del sistema nervioso central en pacientes con VIH en el país.
Describir las infecciones oportunistas en el sistema nervioso central y sus factores demográficos asociados en pacientes con VIH, atendidos en un hospital público de Bogotá.
Presentamos un estudio retrospectivo de tipo serie de casos que incluye a pacientes con VIH/sida ingresados en el Hospital de Santa Clara en el periodo 2015-2016. Se recogieron variables clínicas, paraclínicas y demográficas y el agente etiológico. Además, se realizó una descripción utilizando la prueba Chi², t de Student, U de Mann-Whitney, ANOVA o Kruskal Wallis (significación estadística de p < 0,05)
De 538 pacientes con VIH/sida, 56 tenían una infección oportunista del sistema nervioso central. La mayoría de ellos eran hombres, con una edad media de 37,96 (DE 9,96). El recuento promedio de CD4 fue de 74 cél/μl y la neuroinfección más prevalente fue la toxoplasmosis cerebral.
Las infecciones del sistema nervioso central, diagnosticadas en el Hospital Santa Clara, se asociaron con más de un agente etiológico en algunos de los pacientes. Las infecciones encontradas con mayor frecuencia fueron causadas por Toxoplasma gondii y Cryptococcus neoformans, que tenía altos porcentajes de mortalidad y complicaciones clínicas asociadas.
The opportunistic infections continue to be one of the main causes of morbidity and mortality in HIV-positive; additionally, the central nervous system is one of the most frequently compromised systems. Despite this and the high AIDS mortality rate in Colombia, there are only a few studies that characterize the opportunistic infections of the central nervous system in HIV-positive patients in the country.
To describe the opportunistic infections in the central nervous system and its associated demographic factors in HIV-positive patients, treated in a public hospital of Bogotá.
This study is a retrospective case series study of HIV-AIDS patients hospitalized at Santa Clara Hospital in 2015-2016. Both clinical, paraclinical and demographic variables were collected and a description was made by etiologic agent using the Chi2 test, student t, Mann-Whitney U, ANOVA or Kruskal Wallis (statistical significance of P < 0.05)
From 538 HIV-AIDS patients, 56 had an opportunistic infection of the central nervous system. Most of them were men, with a mean age of 37,96 (SD 9,96). The average CD4 count was 74 cells/μL and the most prevalent neuroinfection was cerebral Toxoplasmosis.
Central nervous system infections, diagnosed at Hospital Santa Clara, were associated with more than one etiologic agent in some of the patients. The most frequently found infections were caused by Toxoplasma gondii and Cryptococcus neoformans; which had high percentages of mortality and clinical associated complications.
Nose to brain delivery of nanosuspensions with first line antiviral agents is alternative treatment option to Neuro-AIDS treatment
2022, Heliyon
Intranasal drug delivery is one of the uprising areas of the research in targeting drug to the brain. Nose to brain drug delivery follows the olfactory pathway and purportedly known to be more efficient to deliver neuro-therapeutics to the brain by circumventing the BBB and thereby increasing bioavailability of drugs in the brain. The advantage of this method is non-invasiveness, rapid onset of action and helps to achieve site specific delivery. In this research work nanosuspension were prepared using combination of antiretroviral agents for Neuro-AIDS treatment. Nanosuspensions were prepared by high-speed homogenization, wet milling and high-pressure homogenization techniques. Formulations were analysed by SEM, FTIR, and DSC. Morphology and stability analysis was done by analysing zeta potential, particle size, and PDI. Ex-vivo diffusion study and histopathological analysis was performed using goat nasal mucosa. High pressure homogenization was found to be best technique for formulation of nanosuspension. Antiviral drugs could be delivered successfully by optimizing nasal dosage form.
Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients
2024, Annals of Clinical Microbiology and Antimicrobials
HIV and COVID-19: two pandemics with significant (but different) central nervous system complications
2024, Free Neuropathology

View all citing articles on Scopus

View full text

ReviewHIV-associated opportunistic infections of the CNS

Summary

Introduction

Section snippets

Biology of HIV-1

Clinical features of CNS opportunistic infections

cART and management of CNS opportunistic infections

Tuberculous meningitis and brain abscesses

Toxoplasmic encephalitis

Cryptococcal meningitis

Cytomegalovirus encephalitis

Progressive multifocal leukoencephalopathy

Primary CNS lymphoma

Herpes simplex virus encephalitis

Conclusions

Search strategy and selection criteria

Pathol Res Pract

Cell

J Neurol Sci

J Neurol Sci

Lancet Infect Dis

Diagn Microbiol Infect Dis

J Infect

J Infect

J Infect

Lancet Infect Dis

Antiviral Res

Mayo Clin Proc

Am J Ophthalmol

J Clin Virol

Global report: UNAIDS report on the global AIDS epidemic, 2010

HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era

Eur J Neurol

NeuroAIDS in the Asia Pacific Region

J Neurovirol

Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa

Clin Infect Dis

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America

MMWR Recomm Rep

Changing incidence of central nervous system diseases in the EuroSIDA cohort

Ann Neurol

Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group

Int J Epidemiol

Nucleotide sequence evidence for relationship of AIDS retrovirus to lentiviruses

Nature

HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5

Nature

Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11 year follow up study

BMJ

Immunopathogenic mechanisms of HIV infection

Ann Intern Med

Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection

N Engl J Med

HIV disease: fallout from a mucosal catastrophe?

Nat Immunol

Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome

J Virol

Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope

J Exp Med

Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy

Science

High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection

N Engl J Med

A decision guideline for emergency department utilization of noncontrast head computed tomography in HIV-infected patients

Acad Emerg Med

Prevalence, associated factors, and prognostic determinants of AIDS-related toxoplasmic encephalitis in the era of advanced highly active antiretroviral therapy

Clin Infect Dis

Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients

Future Microbiol

Progressive multifocal leukoencephalopathy in patients with HIV infection

J Neurovirol

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

J Infect Dis

AIDS-related primary central nervous system lymphoma: a Norwegian national survey 1989–2003

BMC Cancer

Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors

J Neurooncol

Induction and maintenance therapy of cytomegalovirus central nervous system infection in HIV-infected patients

AIDS

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS)

Review
HIV-associated opportunistic infections of the CNS

HIV-1 entry into CD4⁺ cells is mediated by the chemokine receptor CC-CKR-5