hiv treatment and prevention

7/27/2019 HIV Treatment and Prevention

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HIV:

Treatment as Prevention

Christopher KC LeeInfectious Diseases UnitHospital Sungai Buloh


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ARV therapy in the developing world


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Note: at the end of 2011

1110 paediatrics cases on ART


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Access is Improving but not good enough


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Viral Load as a predictor of

Heterosexual HIV transmission

Quinn et al, N Engl J Med. 2000;342:921-929


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HAART stops HIV replication

HIV load falls to undetectable levels in plasma

as well as in sexual fluids

Sharp reduction in HIV transmission


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Impact of ART Sero-discordantHeterosexual Couples

S Attia, M Egger, M Muller, M Zwahlen and N Lowa . AIDS. 2009 Jul 17;23(11):1397-404

92% reduction in HIV Transmission Risk from 5.64 to 0.46

transmissions per 100 person-years


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Cohen et al. N Engl J Med 365;6 August 11, 2011


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Antiviral Treatment as Prevention

Extensive biological plausibility

The concentration of HIV-1 in blood and genital

tract correlates with sexual transmission

Antiretroviral agents that concentrate in the

genital tract reduce HIV-1 viral load

Most observational reports indicate ARTreduces transmission of HIV-1 in couples



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To determine if ART reduces HIV-1transmission

magnitude?

durability of benefit?

To determine if ART is used earlier toreduce HIV-1 transmission

personal health benefit(s)?

A Randomized Controlled Trial



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10,838 Individuals

Screened

Immediate Arm

886 Couples

Delayed Arm

877 Couples

Major reasons for exclusion:

3058 HIV+ but CD4 count out of range

2565 HIV- but HIV+ partner ineligible

308 Seroconcordant couples

155 Ineligible due to sexual history

HPTN 052 Enrollment

1763 Couples

(3526 Individuals)

Randomized



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HPTN 052 Enrollment(Total Enrollment: 1763 couples)

U.S.

Brazil

South AfricaBotswana

Kenya

ThailandIndiamericas

278

Africa954

Asia531imbabwe

Malawi



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Region Site CouplesAmericas

(278)Porto Al egre, Brazil 90Rio de Janeiro , Brazil 186Bo ston , United States 2

Asia(531)Chennai, India 250Pune, Indi a 175Chiang Mai, Thailand 106

Africa

(954)

Gaborone, Botsw ana 77Kisumu, Kenya 60Blanty re, Malawi 230Li longw e, Malawi 251Johannesbu rg, South Afr ica 46Soweto, South Afr ic a 50Harare, Zimb abwe 240

Total 1763

HPTN 052 Enrollment



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Index PartnerImmediate

N = 886Delayed

N = 877Immediate

N = 893Delayed

N = 882Female 49% 50% 49% 47%

Age (median) 33 32 32 32Married 94% 95% 93% 94%

Any unprotected sex 6% 8% 8% 8% CD4 (median [IQR]) 442

[373-522]428

[357-522] --- ---HIV RNA log10(median [IQR])

4.4

[3.8-4.9]4.4

[3.9-4.9] --- ---

HPTN 052: Baseline Characteristics


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Index PartnerImmediate

N = 886Delayed

N = 877Immediate

N = 893Delayed

N = 882Female 49% 50% 49% 47%

Age (median) 33 32 32 32Married 94% 95% 93% 94%

Any unprotected sex 6% 8% 8% 8% CD4 (median [IQR]) 442

[373-522]428

[357-522] --- ---HIV RNA log10(median [IQR])

4.4

[3.8-4.9]4.4

[3.9-4.9] --- ---

HPTN 052: Baseline Characteristics


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Total HIV-1 Transmission Events: 39

HPTN 052: HIV-1 Transmission

Immediate Arm

4

Delayed Arm

35

p < 0.0001



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Total HIV-1 Transmission Events: 39


Linked

Transmissions: 28

Unlinked or TBD

Transmissions: 11

p < 0.001

Immediate

Arm: 1

Delayed

Arm: 27

18/28 (64%) transmissions from infected

participants with CD4 >350 cells/mm3

23/28 (82%) transmissions in sub-Saharan

Africa

18/28 (64%) transmissions from female to

male partners


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Median follow-up: 1.7 years

Study A rm Follow -up (PY)*Incidence/100PY

[95% CI]Linked Overall

Immediate 1585 0.1[0.0 0.4] 0.3[0.1 0.6]

Delayed 1567 1.7[1.1 2.5] 2.2[1.6 3.1]


*Person-years specific for transmission events


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HPTN052: HIV-1 Transmissions


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HPTN 052: Effect of ART

Immediate Arm

Delayed Arm (not on ART)

Delayed Arm (on ART)

3 6 9 12 15 18 21 24 27 30 33 36 39 42 450

Months

Proportion of participants with VL


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HIV Transmission: CD4 Count and HIV-1 RNA

28 Linked Transmissions

Median proximal CD4 (range): 400 (229-858)

Immediate arm: 584 (584-584)

Delayed arm: 391 (229-858)

Median proximal log10 VL (range): 4.9 (2.6-5.8)

Immediate arm: 2.6 (2.6-2.6)

Delayed arm: 4.9 (2.6-5.8)

Immediate

(1)

Delayed

(27)

C

D

4

+(

c

el

ls

/

m

m3)

HI

V

R

N

A(lo

g10

co

pie

s/

m

m3

) Immediate

(1)

Delayed

(27)


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CD4

(cells/mm3

)

P

roportion


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21% initiated therapy

Mostly (75%) triggered by

a decline in CD4 count

Median time to initiation

was 3.5 years

Median CD4 at initiation

was 225 cells/mm3

Q1Q3: 199 247

Time to ART Initiation (Delayed Arm)


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Immediate Arm Delayed Arm

N initiating ART 886 184

(AZT/3TC)/EFV 72% 70%

(AZT/3TC)/ATV 10% 7%

(FTC/TDF)/EFV 9% 11%

(AZT/3TC)/(LPV/RTV) 7% 2%

Other 2% 10%

ART Regimens


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CD4(c

ells/mm3)

Delayed

Immediate

Immediate

Delayed

CD4 Trends Post ART Initiation


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ART response in Immediate arm was rapid and

robust

In Delayed arm ART was initiated in a minority of

participants and was significantly associatedwith baseline CD4 and viral load

Virologic failure was uncommon in either arm

The magnitude of CD4 responses were similar

but the absolute CD4 levels achieved were

lower in the delayed arm

Brief Summary



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Africa Non-Africa

N on ART 615 533

N with evaluable adherence 582 517

Adherence>75% 95% 96%

Adherence>95% 74% 82%

Mean (SD) adherence (%) 95 (12) 95 (15)

Median adherence (%) 99 99

Adherence According to Region


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Treatment for Prevention

Can it work?

Will it work?

Can we afford it?


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TasP in the "Real World"?? Whether substantial population-level reductions in new HIVinfections could be achieved in "real-world" sub-Saharan African

settings where stable, cohabiting couples are often not the norm andwhere considerable operational challenges exist to the successful &sustainable delivery of treatment to large no. of patients.

One of Africa's largest population-based prospective cohort studies (inrural KwaZulu-Natal, SA) followed up a total of 16,667 individuals who

were HIV-uninfected at baseline, observing individual HIVseroconversions over 2004 - 2011. Holding other key HIV risk factorsconstant, individual HIV acquisition risk declined significantly withincreasing ART coverage in the local community.

Conclusion: An HIV-uninfected individual living in a community with

high ART coverage (30-40% of all HIV-infected individuals on ART)was 38% less likely to acquire HIV than someone living in acommunity where ART coverage was low (


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New infections, behaviour change and

treatment coverage in Botswana UNAIDS Report 2011


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hiv treatment and prevention

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