1. THE IMPORTANCE OF EARLY DETECTION IN THE DIAGNOSIS AND PREVENTION OF HIV INFECTIONS
DR. GUILLEMO M. RUIZ-PALACIOS
PROFESSOR AND HEAD
DEPARTMENT OF INFECTIOUS DISAEASES
NATIONAL INSTITUTE OF MEDICAL SCIENCES & NUTRITION
MEXICO

2. Case Presentation Reasons for consultation: 17 y/o male
- 3 wks with fever and malaise
Skin rash and symmetrical lymphadenopathy
Persistent fever despite multiple previous antibiotic treatments

3. Case Presentation History High school student
Uncle diagnosed with TB 3 years ago
Alcohol abuse during weekends
Denies drug abuse
Initiates unprotected sex at 14 years
3 heterosexual partners, not sex workers
Hx of gonorrhea 1 year before

4. Case Presentation Physical exam on admission
BP 120/70 mm Hg, R 90 beats/min, R 20 breaths/min, Temp. 39ºC
cervical lymphadenopathy, no rash
Laboratory
CXR normal
Lymph biopsy: reactive hyperplasia
Blood cultures: Negative 3x

5. Case Presentation Serology HIV 3th Generation EIA: NEGATIVE
Brucella Total Ig: NEGATIVE
Epstein Barr: EBNA Ig (+), VCA IgG (+), VCA IgM (-),
CMV: IgG(+) IgM(-)

6. HIV Serology 27.3 P -- 3.30 15 may 33.7 P 2.65 9 may 0.74 N 4 may
1.80
0.41
2 may Ab Ag
Date
3th Gen.
P.C. = 1.0
4th Gen.
P.C.=0.25

7. Acute Infection Seroconversion by Western Blot
GP160 ►
GP110/120 ►
Acute Infection
Seroconversion by Western Blot
1st sample (May 2) taken 3wks after initiation of symptoms
POL68 ►
GAG55 ►
POLP52 ►
GP41 ►
GAG40 ►
POL34 ►
GAG25 ►
GAG18 ►

8. anti-HIV Ab by Western – Blot
HIV markers of Acute infection
11-12
14-15
20-21
28-29
Time (days)
Viral RNA Ab
Level of detection
P24 antigenemia
HIV RNA
anti-HIV Ab by EIA
Window
anti-HIV Ab by Western – Blot
Acute Infection
P 24

9. Serologic Diagnosis of HIV

10. Detection delay in recognition of HIV infection relative to NAT (days)

11. Detection of Acute Infections during HIV Testing in North Carolina
Pilcher C et al. N Engl J Med 2005;352:

12. Prevalence of HIV Infection in a General Testing
Population , According to Disease Stage
Prevalence of HIV ( no. /1000)
No. at
Risk
Acute Recent Ab Established HIV
All Subjects ,
Man who has sex
with men ,
Victim of sexual
assault
Presence of STD ,
Has a sex partner
at risk ,
Heterosexual contact ,
Does not have an
acknowledged
sex partner ,

13. Frequency of Newly Diagnosed HIV Infections According to Type of Testing Site and Stage of Disease
Pilcher, C. et al. N Engl J Med 2005;352:
Pilcher C et al. N Engl J Med 2005;352:

14. Flow chart of the study population of the Malawi Acute HIV Infection Study
J Infect Dis 2007;195:416-24

15. Prevalence of Established and Acute HIV Infection
in a STD Clinic in Malawi
Population
Established
HIV
Infection
Acute
HIV
Infection
( 40.5 %) (1.45 %)

16. Sensitivity and specificity of rapid tests and p24 antigen
assays for the detection of acute HIV infection
True
Positive, no.
True
negative, no.
False
Positive, no.
False
negative, no.
Sensitivity, %
(95 % CI)
Sensitivity, %
(95 % CI)
Test
Discordant rapid (15-57) (97-99)
Standard p24
antigen (48-93) (97-100)
Up24 antigen (64-99) (96-100)
Note: CI, confidence interval; Up24, ultrasenitive p24

17. Rates of Positivity for HIV-1 for HIV Among Blood Donors
RNA-Positive Donations
Blood Donors
Total
No.
Rate per 106
Donation
(95% CI)
Ratio of First-Time Donors
To repeat Donors
(95% CI)
HIV-1
Total ,164, ( 0.17 – 0.56 )
Otherwise tranfusable ,792,000† ( 0.13 – 0.50 )
First-time ,178,000‡ ( ) ( )§
Repeat ,692,000‡ ( )
† Ninety-nine percent of donations were assumed to be transfusable (nonreactive on all screening tests and suitable for transfusion)
‡ A total of 22.8 percent of donations were assumed to be from first-time donors and 77.3 percent from repeat donors.
§ If calculations were restricted to RNA-positive donations that were nonreactive to HIV-1 p24 antigen, the rates were 0.49 per million first-time donors (95 percent confidence interval, 0.12 to 1.41) and 0.18 per million repeat donors(95 percent confidence interval, 0.6 to 0.43), resulting in ratio of 2.7 (95 percent confidence interval, 0.5 to 12.7).

18. Residual risk of tansfusion-tansmitted viral infections by period of time, France, 1992-2003

19. Residual risk of tansfusion-tansmitted viral infections by period of time, France, 1992-2003

20. Effect of Early Identification of HIV Infection on Life Expectancy
Figure 1. Effect of Early Identification of HIV Infection on Life Expectancy. The solid line represents the effect on life expectancy of identifying asymptomatic HIV infection, as compared with symptom-based case finding. The dashed line represents the effect on quality-adjusted life expectancy.
Sanders G et al. N Engl J Med 2005;352:

21. Cost-effectivness of screening for HIV
Sensitivity Analysis of the Effect of the Prevalence of Unidentified HIV on the Incremental Cost-Effectiveness of One-Time Screening, as Compared with Current Practice (Panel A)
Effect of Screening Frequency on the Incremental Cost-Effectiveness of Screening at Various HIV Incidence Rates (Panel B)
Sanders G et al. N Engl J Med 2005;352:

22. Cost-Effectiveness in HIV Screening of Blood Donation in Ghana
ICER= Incremental cost-effectivness ratio
Van Hulst M et al. Value in Health, 2008 on line

23. Cost-Effectiveness of HIVCTR Strategies in the High-Risk Population Scenario
Figure 1. Cost-Effectiveness of HIVCTR Strategies in the High-Risk Population Scenario. Net program costs are depicted on the horizontal axis and health benefits, measured in quality-adjusted life-months, on the vertical axis. The stand-alone diamond ({diamondsuit}) in the lower left represents the result of current practices for the detection of HIV by means of either background testing of patients or testing of patients who present with an opportunistic infection. The points depict cost and benefit outcomes for enzyme-linked immunosorbent assay (ELISA) and rapid testing at various frequencies: one time (denoted with an X) and every five years, three years, and one year. The slopes of the lines connecting these points represent incremental ratios of effectiveness to cost. The flattening of these lines illustrates the diminishing marginal returns with increased investment in higher-frequency testing.
Paltiel A et al. N Engl J Med 2005;352:

24. Conclusions
Early diagnosis of HIV infection is beneficial for the patient’s health.
Early diagnosis can be achieved through:
-Expanded screening programs in the general population
- The use of new diagnostic methods including: (1) nucleic acid testing (NAT) or (2) the dual ultrasensitive antibody-antigen assays.
Early diagnosis of acute infection plays an important role in transmission control and is a cost-effective intervention.

25. CONFIDENTIAL - to be presented at ICAAC, New-Orleans, Sept 21-24 2005
In the next few years, we may see some light on the control of HIV transmission with the new strategies for the diagnosis of early infection
CONFIDENTIAL - to be presented at ICAAC, New-Orleans, Sept