JOURNAL READING

Presented by : Shinta Tantri Amanda, S.Ked 2008730036 PEMBIMBING : Dr. Rizqa Haerani, Sp.KK

Background

Methods

Results

Discussion

Herpes simplex virus (HSV) type 2 (HSV-2), the most common cause of genital ulcer disease

worldwide , is associated with the prevalence and

incidence of human immunodeciency virus (HIV) .

Little is known about the impact of episodic

treatment of herpes on human immunodeciency virus type 1 (HIV-1).

Background

Methods

Results

Discussion

Several

studies

have

demonstrated

increased

genital shedding of HIV-1 during symptomatic and asymptomatic recurrences of herpetic episodes, suggesting that HSV-2 may increase replication of HIV type 1 (HIV-1), as has been supported by

biological evidence
WHO recommend antiherpetic therapy for patients with genital ulcer disease However, herpes therapy is seldom used in resource-poor settings, and not

Background

Methods

Results

Discussion

The primary aim of the study was to assess the

impact of this intervention on the detection and

quantity of cervicovaginal HIV-1 RNA among HIV1infected women with herpetic ulcers. The secondary aims were to evaluate the impact of the intervention on the detection of lesional

HIV1 RNA, the quantity of plasma HIV-1 RNA, the

detection and quantity of cervicovaginal HSV-2 DNA, and the proportion of healed ulcers.

Background

Methods

Results

Discussion

The Agence Nationale de Recherches sur le SIDA et les He-patites (ANRS) 1212 trial was an individually randomized placebo-controlled trial of

400 mg of acyclovir given 3 times daily for 5 days,

in accordance with standard recommendations, plus antibacterials for the syndromic management of genital ulcer disease.

Background

Methods

Results

Discussion

Women with clinically conrmed ulcers or blisters in African were eligible for recruitment into the study if they were 18 years of age and resided and planned to stay for 1 month. Exclusion criteria :
Menstruation; pregnancy (as determined by urine testing; contraindications to acyclovir (e.g., suspected renal impairment or allergy to acyclovir); and the presence of large ulcers (surface area, 500 mm2), chronic ulcers(duration,11 month), or perianal ulcers only, which prompted provision of open-label acyclovir.

Background

Methods

Results

Discussion

Women who provided consent were interviewed, examined and had genital and blood samples collected Study participants received directly observed single-dose syndromic treatment for chancroid (500mg ciprofloxacin oral) and syphilis (2,4 jt U penicilin IM), counseling about STD and HIV, partner notification slips and condom. Participants were asked to return to the clinic on day 2 and/or day 4 and on days 7,14, and 28 At each clinic visit, a pelvic examination and genital samples collected

Background

Methods

Results

Discussion

Specimen collection and laboratory procedures. Study denitions. HIV-1 infection as detec-tion of HIV-1 either in a cervicovaginal lavage specimen or serologically. A nonprimary rst episode of genital HSV-2 infection was dened as detection of HSV-2 DNA in the lesion of or cervicovaginal lavage specimen obtained from women who were HSV-1 seropositive and HSV-2 seronegative. We used 2 denitions of ulcer healing at each clinic visit: (1) a 90% reduction in the surface area of the largest ulcer, compared with its size at D0, and (2) the proportion of patients whose largest ulcer was 10 mm2 .

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Impact on cervicovaginal, lesional, and plasma HIV-1 RNA.

The proportion of women in the acyclovir group who had detectable cervicovaginal HIV-1 RNA decreased from 80% at D0 to 71% at D7, but there was no evidence of an impact of acyclovir on detectable cervicovaginal HIV-1 RNA.

Impact of acyclovir on cervicovaginal HSV-2 DNAand ulcer healing.

Women receiving acyclovir were less likely to have detectable cervicovaginal HSV-2 at D7 than were women receiving placebo (RR, 0.69; 95% CI, 0.41.3) (table 2), and among those with detectable virus at D7, the quantity

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Figure 3. Rates of ulcer healing (as

determined
analysis)

by
among

Kaplan-Meier
118 virus human type 1

immunodeciency

infected women with herpes simplex virus type 2 ulcers in Ghana and the Central African Republic. * P=.21 was estimated from Cox regression,

with ulcer healing dened as a 90%

reduction in ulcer size.

Background

Methods

Results

Discussion

In HIV1infected women with HSV-2 ulcers, there was

no effect of acyclovir on cervicovaginal and plasma

HIV-1, some evidence of reduction in lesional shedding of HIV-1 and of reduced frequency and quantity of cervicovaginal shedding of HSV-2, and only modest improvements in ulcer healing.

To our knowledge, the rst randomized trial evaluating

the impact of episodic antiviral therapy for HSV-2 added to syndromic management on HIV-1 outcomes

Background

Methods

Results

Discussion

The rationale for this study was multifold First, epidemiologic and biological evidence has suggested an important role of HSV in enhancing HIV

replication and, possibly, transmission. Clinical and

subclinical reactivation of genital HSV-2 has been associated with increases in HIV-1 genital shedding and plasma HIV-1 loads and observational studies of HSV episodic therapy have shown that acyclovir has a

role in reducing lesional and plasma HIV-1 levels

Background

Methods

Results

Discussion

Second, the strong association of HIV transmission with genital ulcer disease

suggests that a substantial proportion of HIV transmissions may take place during clinical ulcer episodes, including in settings where the majority of ulcers are caused by HSV-2

Background

Methods

Results

Discussion

Because the majority of ulcers in developing countries are caused by HSV-2, particularly among HIV-positive patients, the World Health Organization recommends adding acyclovir

o antibacterial syndromic management. However, data on the

effectiveness of this strategy in developing countries, is lacking The results suggest that currently recommended HSV therapy does not dramatically improve ulcer healing, has only

a modest effect on HSV-2 shedding, and could not inhibit the

replication of HIV-1 in the genital tract or plasma.

Background

Methods

Results

Discussion

The postulated mechanism of impact is that, by reducing

reactivations of HSV-2, herpes-suppressive therapy is able to

prevent HIV replication by disrupting direct viral interactions and, indirectly, by reducing the systemic and local immune activation induced by HSV-2. HSV-2 genital shedding is associated with increased levels of HIV1 target cells (i.e., activated CD4 T lymphocytes) within the genital mucosa. This response may increase replication of genital HIV-1 in

HIV-1infected individuals.

Background

Methods

Results

Discussion

Limitation of this study is :

A pragmatic trial
Unbalanced characteristics. Our nal sample size Was also slightly smaller than that estimated by the groups for some baseline

power calculations
Exclusion (for ethical reasons) of patients with more-severe herpetic ulcers may limit the

conclusion
In conclusion, our results indicate that, among HIV-infected women, the use of acyclovir in accordance with current recommendations for the management of genital ulcer

disease due to HSV-2 had only a weak effect on the course of

the ulcers and HSV-2 genital shedding, and it did not reduce systemic and genital HIV replication. Our results do not support the hypothesis that providerinitiated short-course acyclovir therapy effectively disrupts genital interactions between HIV-1 and HSV-2 or that such