Presentation is loading. Please wait.

Presentation is loading. Please wait.

D-HIV Diagnosis, Acute Infection and Superinfection

Similar presentations


Presentation on theme: "D-HIV Diagnosis, Acute Infection and Superinfection"— Presentation transcript:

1 D-HIV Diagnosis, Acute Infection and Superinfection

2 Objectives Discuss the diagnosis of HIV and available tests
Describe the approach to the diagnosis of acute retroviral syndrome Debate the advantages and disadvantages of early treatment of acute HIV infection Discuss the evidence for the possibility of superinfection / reinfection and the implications for patient education and management

3 Anonymous vs Confidential
Identifying information not provided Results not linked to identifying information Allows reporting of HIV infection without breaching confidentiality Disadvantage: may not be able to locate clients for test results Confidential Clients linked to test result by identifying information Results remain confidential Informed consent

4 Pre-Test Counseling Goal: reduce HIV acquisition and transmission
Accurate and current information about HIV Obtain informed consent Transmission and acquisition HIV test info: risk, benefits, meaning of potential test results Assessment of individuals risks and appropriate risk reduction activities Capacity to comprehend HIV testing and consent

5 Post-Test Counseling Accurate and current information about HIV
Local resources Risk reduction education Referrals for ongoing care and support Healthy living strategies Meaning of test results and state reporting guidelines Mental health support / counseling

6 Diagnosis of HIV Infection
Viral antibodies Viral antigens Viral RNA/DNA Culture

7 Enzyme Immunoassay Enzyme-Linked Immunosorbent Assay (EIA, ELISA)
Primary HIV antibody screening test Serum plasma, dried blood spots, oral fluids, urine HIV-1/2, HIV-1, HIV-2 High degree sensitivity and specificity Repeatedly reactive: confirmatory testing

8 Negative Antibody Test Results
HIV negative Recent infection: too early for seroconversion CDC: follow-up testing at 6 weeks, 12 weeks, 6 months

9 Confirmation Process Non-negative screenings should be confirmed
Western Blot (WB) Immunofluorescent Antibody Assay (IFA) Higher specificity than EIA Interpretation can be subjective

10 Predictive Value: HIV Ab Tests
Depends on the prevalence of HIV infection in the population Low HIV prevalence: predictive value of a positive test is low HIV Ab testing of low prevalence populations likely to produce more false-positive than true-positive results

11 Window Period Time delay from infection to positive EIA
Average: days Most seroconvert within six months

12 HIV-1 vs HIV-2 HIV-1: Most cases
Group M: predominant strain world-wide Subtypes (clades): A to K, N, O Clade B US and Europe 98% of HIV-1 in US Most non-B subtypes were acquired outside US Clade C: Southeast Asia N (“new”): 1998 Group O: West Africa Recombination between viruses of different clades becoming more common

13 Predominant HIV-1 Subtypes
A: West/East/Central Africa, East Europe, Mideast B: North America, Europe, Mideast, East Asia, Latin America C: South Africa, South Asia, Ethiopia D: East Africa E: Southeast Asia

14 HIV-2 Primarily found in West Africa
Causes immune deficiency due to depletion of CD4 cells 5-8 fold less efficient transmission compared to HIV- 1 Associated with lower viral load Slower rate of CD4 decline and clinical progression Negative Ab tests in 20-30% depending on EIA assay WB: not well standardized nor FDA approved

15 Testing Recommendations: HIV-2
Natives of endemic areas Needle-sharing and sex partners of persons from endemic areas Sex or needle-sharing partners of persons with known HIV-2 infection Transfusion or non-sterile injection recipients in endemic areas Children of HIV-2 infected women

16 HIV-2 Endemic Areas Benin Burkina Faso Cape Verde Cote d’Ivoire Gambia
Ghana Guinea Guinea-Bissau Liberia Mali Mauritania Niger Nigeria Sao Tome Senegal Sierrra Leone Togo West Africa Other Mozambique Angola

17 Confirmation Process: WB
Detects antibodies to HIV-1 proteins Core: p17, p24, p55 Polymerase: p31, p51, p66 Envelope: gp41, gp120, gp160 Negative: no bands Positive: Reactivity to gp41 + gp120/160 or Reactivity to p24+gp120/160 Indeterminate: EIA repeatedly reactive Presence of any band pattern not meeting criteria for positive results

18 False Negative Results
High-prevalence population: 0.3% Low-prevalence: <0.001% Usually due to testing during window period Rare patients seroconvert in late-stage disease Technical or clerical error Type N or O HIV-2

19 False Positive Test Results
Much less common than in earlier times Frequency: % to % Causes Autoantibodies (single case, Lupus, ESRD) HIV vaccines EIA+: 68% WB+: 0-44% Technical / clerical error

20 Indeterminate Results
4-20% of WB assays with positive bands Testing during seroconversion p24 usually appears first Late stage HIV: loss of core antibody HIV vaccine recipients Technical / clerical error Infection with O strain or HIV-2

21 Indeterminate Results (continued)
Cross-reacting nonspecific antibodies Collagen-vascular disease Autoimmune disease Pregnancy Organ transplantation Lymphoma, other malignancies Liver disease Multiple sclerosis Recent immunization

22 Indeterminate Results
Evaluate HIV risk Low risk: almost never infected with HIV-1 or HIV-2 Repeat testing: often continued indeterminate Cause: frequently not established HIV unlikely Follow-up serology in 3 months Seroconversion: usually WB+ in 1 month Repeat testing at 1, 2, 6 months Counseling to reduce potential transmission

23 Frequency of HIV Testing
High risk behavior: every 6-12 months Annual seroconversion General population: 0.02% Military recruits: 0.04% MSM: % IDU in high prevalence area: 0.7-6%

24 Alternative Testing Home test kits Rapid Testing
Alternative body fluids Saliva Urine Vaginal secretions Viral detection

25 Home Testing Home specimen collection
Self-dried blood spot obtained with lancet Anonymous coding Mail/courier to testing facility Double EIA and confirmatory IFA/WB Sensitivity/Specificity: ~100% Results relayed to user by telephone after user initiates request Negative: prerecorded message Positive: live conversation and counseling

26 Rapid HIV Antibody Detection
Results in minutes Occupational exposure Women in labor with unknown HIV status Clients unlikely to return for visits Outreach ERs

27 Rapid HIV Antibody Detection
OraQuick HIV-1 Antibody Test (OraSure) Results read by provider in 20 minutes Sensitivity: 99.6% / Specificity: 100% $20-30 Testing initially delayed due to CLIA requirements Fingerstick sample of blood Negative test: definitive Positive test: needs standard serology confirmation Not recommended for HIV-2 screening

28 Rapid HIV Antibody Detection
Single Use Diagnostic System (SUDS) HIV-1 Test Venipuncture Results: minutes Confirmatory WB required Double Check (Organies)

29 Type N, Type O, HIV-2 EIA may fail to detect O subtype
N group: causes false-negative EIA but may be WB positive HIV-2: false negative EIA in 20-30% Consider specific HIV-2 testing

30 P24 Antigen Part of blood bank algorithms since 1996
Uncommon in clinical practice Detects free, non-complex HIV antigens in peripheral blood

31 Typical Course of Primary HIV
1 mil HIV RNA Typical Sequence of Events in Primary HIV Event Day Infection 0 Entry of virus into bloodstream 3-7 Detectable HIV-1 RNA 7-14 Detectable p24 antigen 12-19 Onset of symptoms 14-28 Antibody seroconversion 30-60 most patients who contract HIV are symptomatic with seroconversion flu-like or mono-like illness often accompanied by a rash onset typically 3-4 weeks following exposure, but high variability growing evidence that treatment of PHI may have significant long-term benefit HIV RNA 100,000 + HIV-1 Antibodies _ 10,000 Ab P24 + 1,000 Exposure 100 Symptoms 10 20 30 40 50 Days

32 Rapid Test Results Reactive (preliminary positive) rapid test
Screening test is positive Preliminary result Confirmatory testing required Precautions to avoid viral transmission Negative rapid test No recent exposure: definitive negative Possible recent exposure: Recommend re-test Counseling to prevent transmission A simple way to phrase this message could be, “Your screening test result is positive, but this is only a preliminary test, and we will not know for sure if you are HIV-infected until we get the results of your confirmatory test. In the meanwhile, you should take precautions to avoid the possibility of transmitting the virus to others. These precautions include …” Depending on the setting, the client’s needs and expectations, and the provider’s level of knowledge, it may be possible to elaborate on this message. But the primary need is to be sure the client understands the simple message and returns for the results of confirmatory testing

33 OraQuick: Florida DOH 6 Month Pilot Studies Hillsborough CHD
Duval County Jail Orlando CBO for substance abuse Miami: 2 sites Key West: only anonymous site

34 Saliva Testing: OraSure
EIA and WB to detect IgG Specimen collection device, antibody screen, WB confirmation Cost: ~$25 Specially treated pad placed between lower cheek and gum for 2 minutes Vial sent to lab for processing Sensitivity and specificity comparable to standard serologic testing (~99.5%) Advantages: ease of collection; low cost; improved patient acceptance Disadvantage: client must return for results

35 Urine Testing Calypte HIV-1 Urine EIA
Positive results require standard serologic confirmation Sensitivity: 99%; Specificity: 94% Cost: ~$4

36 Vaginal Secretions IgG EIA CDC: recommended for rape victims
Semen contains HIV IgG Ab

37 Indications for HIV Viral Detection
Confusing / indeterminate serologic test results Acute retroviral infection Neonatal infection Window period following exposure Not FDA approved for diagnosis of HIV Expensive

38 Viral Detection p24 Antigen HIV-1 DNA PCR HIV-1 RNA (RT-PCR, bDNA)
Most sensitive: able to detect 1-10 copies of proviral DNA S/S: 99% / 98% HIV-1 RNA (RT-PCR, bDNA) S/S: 95-98% Viral culture of PBMC: expensive, labor intensive, reliability variable

39 Viral Detection: HIV-2 bDNA proficient at quantitation of many non- clade B viruses Amplicor version 1.5 designed to detect other clades

40 National Recommendations For HIV Testing of Pregnant Women
USPHS Recommendations for HIV Screening of Pregnant Women ( ) Universal testing for all pregnant women as a routine part of prenatal care using an “opt out” approach Labor and Delivery: routine rapid testing if HIV status unknown Postnatal: rapid testing for all infants whose mother’s status is unknown Regulations, laws, and policies about HIV screening of pregnant women vary from state to state

41 Acute HIV Infection

42 Acute HIV Infection Transient symptomatic illness in 40-90%
Usually mild but can be severe 2-6 weeks after infection Often not recognized by primary care clinicians Symptoms non-specific Often resembles influenza, mononucleosis “Cold symptoms” absent Can be asymptomatic Duration: 14 days

43

44 Acute HIV Infection Fever 96% Headache 32% LAD 74% N/V 27% Pharyngitis
70% HSM 14% Rash Wt loss 13% Myalgia/arthralgia 54% Thrush 12% Diarrhea Neuro Sx Neuro: meningoencepalitis or aseptic meningitis; peripheral neuropathy or radiculopathy; facial palsy, Guillain-Barre syndrome; brachial neuritis; cognitive impairment or psychosis

45 Rash in Acute HIV Infection
Trunk, face, extremities Palms and soles rarely involved 5-10 mm diameter Erythematous, nonpruritic, painless

46 Laboratory Findings Acute HIV Infection
Lymphopenia → lymphocytosis Atypical lymphocytes Transient CD4 decline VL: 100,000 – 1,000,000

47 Diagnosis of Acute HIV Infection
Recognition of clinical symptoms No true constellation of signs/sympoms Presence of any symptom(s) History of activity associated with HIV risk Detectable plasma HIV RNA Highly sensitive False positive possible Detectable p24 Antigen Less sensitive False positive rare

48 Acute HIV Infection High virus levels (105-106 copies/mL)
2-9% of HIV-negative have false positive results Usually associated with low RNA titers <10,000 VL in new infections Correlates with rate of CD4 decline Prognostic indicator in early disease

49 Potential Benefits: Early Intervention
Decrease the severity of acute disease Alter initial viral set point → alter disease progression rate Suppress viral replication → reduce rate of viral mutation Preserve HIV-specific immune responses May permit future discontinuation of therapy with sustained viral control Reduce risk for viral transmission May minimize viral evolution and development of viral diversity

50 Potential Risks: Early Intervention
Decreased QOL Medication side effects Drug toxicities Dosing constraints Drug resistance if viral suppression inadequate Need for indefinite continuing therapy Expensive Potential for transmission of resistant virus

51 Potential Risks: Early Intervention
Long term clinical outcome benefit has not been documented Additional studies are needed to delineate the role of ARV therapy during the primary infection period

52 Treatment: Acute HIV Infection
Weigh potential benefits against potential risks “Certain authorities endorse treatment of acute HIV infection on the basis of the theoretical rationale and limited but supportive clinical trial data”

53 Treatment: Acute HIV Infection
Experienced clinicians recommend consideration of therapy for patients among whom seroconversion has occurred within the previous 6 months “Although the initial burst of viremia among infected adults usually resolves in 2 months, treatment during the 2 to 6-month period after infection is based on the probability that virus replication in lymphoid tissue is still not maximally contained by the immune system during this time”

54 Detuned Antibody Testing
Less sensitive ELISA test May help distinguish between recent seroconverters and those with long-standing HIV infection Current ELISAs can detect relatively low levels of Ab HIV Ab levels increase over first few months Recent infection: standard ELISA positive Detuned assay: negative Able to diagnose individuals who have already seroconverted on a standard ELISA but are still early in infection

55 HIV Superinfection

56 HIV Super-Infection Coinfection with a second strain of HIV during the course of established HIV-1 infection (Jost, NEJM 347:10, 2002) Known to be theoretically possible Little direct evidence to support concept

57 HIV Superinfection 2000: LTNP (patient A) – unprotected intercourse with ARV-experienced male with progressive HIV disease (patient B) Patient A experienced rapid disease progression Virus harbored original strain and drug- resistant strain from patient B

58 HIV Superinfection Established infection with HIV-1, subtype AE
Well-controlled viremia on HAART; unable to remain on ART due to liver toxicity Sexual exposure to type B in Brazil Unprecedented rise in viral load and rapid CD4 depletion Mixture of B and AE identified Rapid emergence of type AE

59 HIV Superinfection Evidence supports clades from different geographic areas have combined Likely due to superinfection of an individual harboring a virus of one clade with a second virus of another clade

60 SIV Superinfection SIV superinfection in monkeys may occur, probably rare Difficult to superinfect a monkey with established SIV even with High infectious dose IV administration Possible when challenged with second SIV strain during or soon after initial infection with first strain Possible “window of opportunity” for superinfection

61 SIV Superinfection Development of virus-specific immunity over time
Primary infection: immunity absent or too immature to effectively prevent infection Strengthening of virus-specific immune responses → superinfection less likely

62 Superinfection Implications for HC Providers
Consider the possibility of superinfection Counsel patients regarding sexual practices and safer sex

63 Summary Significant advances in assays to detect HIV infection
Alternatives to standard EIA/WB testing may facilitate improved, ongoing HIV screening Detection of acute HIV infection needs to enhanced Early intervention in acute HIV infection may have clinical benefits Superinfection needs to be considered Risk reduction counseling must be ongoing


Download ppt "D-HIV Diagnosis, Acute Infection and Superinfection"

Similar presentations


Ads by Google