IDIBAPS - Hospital Clínic de Barcelona

Universitat de Barcelona (Spain)

Identification of symptomatic acute and recent HIV infection in a rural area of

southern Mozambique

Cèlia Serna Bolea

Total: 33.2 (30.6 – 36.1) million

Western & Central Europe

610 000[480 000 – 760 000]

North Africa & Middle East540 000

[230 000 – 1.5 million]

Sub-Saharan Africa22.5 million

[20.4 – 29.4 million]

Eastern Europe & Central Asia1.4 million

[920 000 – 2.1 million]

South & South-East Asia7.1 million[4.4 – 10.6 million]

Oceania35 000

[25 000 – 48 000]

North America1.0 million

[540 000 – 1.6 million]

Caribbean440 000

[270 000 – 780 000]

Latin America1.7 million

[1.3 – 2.2 million]

East Asia1.1 million

[560 000 – 1.8 million]

SSA: 68% of all HIV infections

INTRODUCTION

ADULTS AND CHILDREN LIVING WITH HIV/AIDS IN 2007

INTRODUCTION

PHASES OF HIV INFECTION

Antibodies against HIV

Recent infection

INTRODUCTION

• During AHI and early phases: high levels of HIV RNA (higher for subtype C) more likely to transmit HIV infection. (Dyer JR, JID: 1998; Pilcher CD, AIDS:2007)

• AHI and early months of HIV infection may contribute disproportionally to the transmission of HIV (Pilcher CD, JID: 2004; Cohen MS, JID: 2005)

• 50% of onward transmissions occur in the first 6 months after infection (Brenner BG, JID: 2007)

IMPORTANCE OF DETECTING ACUTE HIV INFECTION (AHI) AND RECENT INFECTION CASES

• AHI very challenging to diagnose:

• Half of the patients develop non-specific flu-like or mononucleosis-like symptoms (MN)

• The remaining AHI are asymptomatic and go unnoticed (Schacker T, AnInt Med 1996)

INTRODUCTION

• Sexual Transmitted Infection (STI) clinics• Voluntary Counselling and Testing centres (VCT)

– Prevalence of HIV is high

• Antenatal Clinics– Prevalence of HIV high and risk for mother to child transmission (MTCT)

may be greater during AHI

• Outpatient triage in areas of high malaria prevalence– People accustomed to presenting for fever for malaria testing

Potential populations for screening in sub Saharan Africa

DIFFICULT DIAGNOSIS of AHI and RECENT INFECTIONS

OBJECTIVES

1. To determine prevalence of AHI within the adult HIV seronegative population presenting with reported fever to the outpatient ward.

2. To determine prevalence of recent HIV infection within patients with discordant/positive rapid test attending at Voluntary Counseling Testing (VCT).

MANHIÇA DISTRICT

Mozambique, southeast Africa

approximately 21 million inhabitants

Manhiça District Hospital (MDH)

Manhiça Health Research Centre (CISM)

Demographic Surveillance System (DSS)

82.000 inhabitants in 400 km2

STUDY SITE (in Manhiça district, Mozambique)

METHODOLOGY

METHODOLOGY

STUDY DESIGNProspective Observational Study

STUDY GROUPS

1) AHI group

To assess the prevalence of acute HIV-1 infections in adults presenting with fever

2) Recent Infected group

To assess the prevalence of recent infections in this adults presenting at VCT

ScreeningHIV RNA detection (pooling)

ScreeningBED Incidence EIA

InclusionHIV negative serologyHIV RNA positive

InclusionRecent infected patients <6mo

Study populationPeople attending the outpatient ward with:

-Fever/ reported fever -Not under followup in the HIV day hospital-HIV negative serology

Study population

People attending the VCT with:

-Discordant/ positive HIV serology

PHASES OF HIV INFECTION

Antibodies against HIV

RESULTS AHI

RESULTS AHI

125 refusals

472 subjects presenting with reported feverat outpatient ward

131 HIV-1 positive

346 acceptedtesting

4 refused blood draw

215 HIV-1 negative

209 HIV-1 RNA negative

211 HIV-1 negative

with blood sample

6 attended followup visits

1 lost to follow-up

7 HIV-1 RNA positive

37.8%

3.3%

RESULTS AHI

Malaria

A H I

Other aetiology

13%3.3% (95% CI, 1.3-6.7)

AETIOLOGY of REPORTED FEVER IN HIV-SERONEGATIVE ADULTS

83.7%

RESULTS AHI

Clinical immunological and virological features of AHI patients

* Expressed as log10 copies/mL **MN=mononucleosis-like symptoms, R=respiratory, GI=gastrointestinal, P= pharyngitis, S=evidence of sexually transmitted infection (discharge, dysuria) except for ulcer, U=genital ulcer, LTFU=Lost to follow-up

Subject Sex Age

HIV-RNA*

Symptoms** (d7)

CD4cnt CD4:CD8

% Activated

CD8

(d0) (d7) (d7) (d7)

 

67 F 31 6.09 MN, R, S, P 850 0.30 67.7

101 M 34 ND MN, R, GI, P 239 0.55 59.3

148 M 40 6.88 R, GI, S, P 441 0.40 59.6

188 M 34 5.92 MN, R, P 413 0.36 69.1

197 M 59 6.41 U, P 180 0.10 94.7

221 F 57 6.32 MN, R, GI, S,P 355 0.63 87.8

212 M 30 3.35 LTFU ND ND ND

Median

   

6.21   384 0.38 68.4

(IQR) (5.92-6.41) (239-441) (0.30-0.55) (59.6-87.8)

PHASES OF HIV INFECTION

Antibodies against HIV

Recent infection

RESULTS RECENT

493 subjects referred from VCT

482 HIV-1 positive

11 HIV-1 serodiscordant

81/493Recent Infections

BED-EIA

16.4%

RESULTS RECENT

 

HIV-1 +n (%)

HIV-1 Discordan

tn (%)

MEDIANVIRAL LOAD*

CD4<200 cel/µL*

HIV RECENT INFECTED

n=81

71/482 14.7% 11/11 100% 4.98 log10 cop/mLIQR (4.22-5.43)

19/75 25.3%

RESULTS RECENT

General characteristics of recent infected patients

* All values do not add up to 81 due to missing data 16.4% BED-EIA

12.6% BED-EIACD4>200

• High prevalence of AHI: 3.3% (95% CI, 1.3-6.7) among adults presenting with reported fever in an outpatient ward

• AHI patients had high median viral load: 6.21 log10 copies/mL similar to values of AHI for subtype C in other African settings, higher than other subtypes

• Percentage of activated CD8+ T lymphocytes similar to that reported in chronically HIV infected Africans

• Malaria-like, mononucleosis-like symptoms and pharyngitis could be relevant syndromes to target AHI

• Prevalence of undiagnosed established HIV infection in this population was 37.8% (95% CI, 32.7-43.2), higher than in previous estimations

• From HIV infections diagnosed at VCT 16.4% were determined to be recent infections according to BED-EIA but over 25% had CD4<200

CONCLUSIONS

DISCUSSION

• Using BED-EIA test as an screening tool in areas with high HIV prevalence can overestimate recent infections in this population

• Simplified HIV RNA detection methods are necessary in resource limited settings (e.g. p24 from dry blood spots)

• Screening for AHI as a novel prevention approach in areas with high HIV prevalence:

• WHY?• Acute HIV is highly infectious

• WHO?• Target populations:

• Fever in malaria endemic areas• STI clinics

• HOW?• Case finding of AHI and counseling effective for short term risk modification

Acknowledgments

Denise NanicheJose Muñoz

Emilio Letang

Pedro Alonso

Jose M. AlmeidaAriel Nhacolo

Tacilta NhampossaEliana Ferreira

Eusebio Macete

Field staff

Apollinario NzangoNelito JoséElsa Banze

Lucas NhatumboRoque Singaril Vilanculo

Atanasio Chirinze