Episodic Therapy for Genital Herpes in Sub-Saharan Africa: A Pooled Analysis from Three Randomized Controlled Trials
Identifieur interne : 000828 ( Main/Exploration ); précédent : 000827; suivant : 000829Episodic Therapy for Genital Herpes in Sub-Saharan Africa: A Pooled Analysis from Three Randomized Controlled Trials
Auteurs : Helen A. Weiss [Royaume-Uni] ; Gabriela Paz Bailey [Guatemala] ; Sam Phiri [Malawi] ; Gerard Gresenguet [République centrafricaine] ; Jerome Legoff [France] ; Jacques Pepin [Canada] ; David A. Lewis [Royaume-Uni, Afrique du Sud] ; Laurent Belec [France] ; Irving F. Hoffman [États-Unis] ; William C. Miller [États-Unis] ; Philippe Mayaud [Royaume-Uni]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Descripteurs français
- KwdFr :
- ARN viral (métabolisme), Aciclovir (usage thérapeutique), Adolescent, Adulte, Afrique subsaharienne, Femelle, Herpès génital (), Herpès génital (traitement médicamenteux), Herpès génital (virologie), Humains, Jeune adulte, Mâle, Séropositivité VIH (), Ulcère (), Ulcère (traitement médicamenteux), Ulcère (virologie), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie).
- MESH :
- immunologie : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- métabolisme : ARN viral.
- traitement médicamenteux : Herpès génital, Ulcère.
- usage thérapeutique : Aciclovir.
- virologie : Herpès génital, Ulcère.
- Adolescent, Adulte, Afrique subsaharienne, Femelle, Herpès génital, Humains, Jeune adulte, Mâle, Séropositivité VIH, Ulcère, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Acyclovir (therapeutic use), Adolescent, Adult, Africa South of the Sahara, Female, HIV Seropositivity (complications), HIV-1 (drug effects), HIV-1 (immunology), Herpes Genitalis (complications), Herpes Genitalis (drug therapy), Herpes Genitalis (virology), Humans, Male, RNA, Viral (metabolism), Ulcer (complications), Ulcer (drug therapy), Ulcer (virology), Young Adult.
- MESH :
- chemical , metabolism : RNA, Viral.
- chemical , therapeutic use : Acyclovir.
- geographic : Africa South of the Sahara.
- complications : HIV Seropositivity, Herpes Genitalis, Ulcer.
- drug effects : HIV-1.
- drug therapy : Herpes Genitalis, Ulcer.
- immunology : HIV-1.
- virology : Herpes Genitalis, Ulcer.
- Adolescent, Adult, Female, Humans, Male, Young Adult.
Abstract
A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations.
Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm2), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors.
There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing.
Url:
DOI: 10.1371/journal.pone.0022601
PubMed: 21799914
PubMed Central: 3143155
Affiliations:
- Afrique du Sud, Canada, France, Guatemala, Malawi, Royaume-Uni, République centrafricaine, États-Unis
- Angleterre, Caroline du Nord, Gauteng, Grand Londres, Île-de-France
- Johannesbourg, Londres, Paris
- Université du Witwatersrand
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Le document en format XML
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Weiss</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>London School of Hygiene and Tropical Medicine, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London School of Hygiene and Tropical Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Paz Bailey, Gabriela" sort="Paz Bailey, Gabriela" uniqKey="Paz Bailey G" first="Gabriela" last="Paz Bailey">Gabriela Paz Bailey</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Del Valle University of Guatemala, Guatemala and Tephinet Inc, Decatur, Guatemala</addr-line></nlm:aff><country xml:lang="fr">Guatemala</country><wicri:regionArea>Del Valle University of Guatemala, Guatemala and Tephinet Inc, Decatur</wicri:regionArea><wicri:noRegion>Decatur</wicri:noRegion></affiliation></author><author><name sortKey="Phiri, Sam" sort="Phiri, Sam" uniqKey="Phiri S" first="Sam" last="Phiri">Sam Phiri</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Lighthouse Trust, Lilongwe, Malawi</addr-line></nlm:aff><country xml:lang="fr">Malawi</country><wicri:regionArea>Lighthouse Trust, Lilongwe</wicri:regionArea><wicri:noRegion>Lilongwe</wicri:noRegion></affiliation></author><author><name sortKey="Gresenguet, Gerard" sort="Gresenguet, Gerard" uniqKey="Gresenguet G" first="Gerard" last="Gresenguet">Gerard Gresenguet</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Centre National de Référence pour les Maladies Sexuellement Transmissibles, Bangui, Central African Republic</addr-line></nlm:aff><country xml:lang="fr">République centrafricaine</country><wicri:regionArea>Centre National de Référence pour les Maladies Sexuellement Transmissibles, Bangui</wicri:regionArea><wicri:noRegion>Bangui</wicri:noRegion></affiliation></author><author><name sortKey="Legoff, Jerome" sort="Legoff, Jerome" uniqKey="Legoff J" first="Jerome" last="Legoff">Jerome Legoff</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Paris Diderot University and Laboratoire de Virologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Diderot University and Laboratoire de Virologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Pepin, Jacques" sort="Pepin, Jacques" uniqKey="Pepin J" first="Jacques" last="Pepin">Jacques Pepin</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Université de Sherbrooke, Sherbrooke, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Université de Sherbrooke, Sherbrooke</wicri:regionArea><wicri:noRegion>Sherbrooke</wicri:noRegion></affiliation></author><author><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>London School of Hygiene and Tropical Medicine, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London School of Hygiene and Tropical Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg</wicri:regionArea><wicri:noRegion>Johannesburg</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>University of the Witwatersrand, Johannesburg, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>University of the Witwatersrand, Johannesburg</wicri:regionArea><orgName type="university">Université du Witwatersrand</orgName><placeName><settlement type="city">Johannesbourg</settlement><region type="region" nuts="2">Gauteng</region></placeName></affiliation></author><author><name sortKey="Belec, Laurent" sort="Belec, Laurent" uniqKey="Belec L" first="Laurent" last="Belec">Laurent Belec</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Paris Diderot University and Laboratoire de Virologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Diderot University and Laboratoire de Virologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hoffman, Irving F" sort="Hoffman, Irving F" uniqKey="Hoffman I" first="Irving F." last="Hoffman">Irving F. Hoffman</name><affiliation wicri:level="2"><nlm:aff id="aff9"><addr-line>University of North Carolina, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of North Carolina, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Miller, William C" sort="Miller, William C" uniqKey="Miller W" first="William C." last="Miller">William C. Miller</name><affiliation wicri:level="2"><nlm:aff id="aff9"><addr-line>University of North Carolina, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of North Carolina, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Mayaud, Philippe" sort="Mayaud, Philippe" uniqKey="Mayaud P" first="Philippe" last="Mayaud">Philippe Mayaud</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>London School of Hygiene and Tropical Medicine, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London School of Hygiene and Tropical Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acyclovir (therapeutic use)</term><term>Adolescent</term><term>Adult</term><term>Africa South of the Sahara</term><term>Female</term><term>HIV Seropositivity (complications)</term><term>HIV-1 (drug effects)</term><term>HIV-1 (immunology)</term><term>Herpes Genitalis (complications)</term><term>Herpes Genitalis (drug therapy)</term><term>Herpes Genitalis (virology)</term><term>Humans</term><term>Male</term><term>RNA, Viral (metabolism)</term><term>Ulcer (complications)</term><term>Ulcer (drug therapy)</term><term>Ulcer (virology)</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (métabolisme)</term><term>Aciclovir (usage thérapeutique)</term><term>Adolescent</term><term>Adulte</term><term>Afrique subsaharienne</term><term>Femelle</term><term>Herpès génital ()</term><term>Herpès génital (traitement médicamenteux)</term><term>Herpès génital (virologie)</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Séropositivité VIH ()</term><term>Ulcère ()</term><term>Ulcère (traitement médicamenteux)</term><term>Ulcère (virologie)</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Acyclovir</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Africa South of the Sahara</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>HIV Seropositivity</term><term>Herpes Genitalis</term><term>Ulcer</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Herpes Genitalis</term><term>Ulcer</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN viral</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Herpès génital</term><term>Ulcère</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Aciclovir</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Herpès génital</term><term>Ulcère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Herpes Genitalis</term><term>Ulcer</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Female</term><term>Humans</term><term>Male</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Afrique subsaharienne</term><term>Femelle</term><term>Herpès génital</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Séropositivité VIH</term><term>Ulcère</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations.</p></sec><sec><title>Methodology/Principal Findings</title><p>Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm<sup>2</sup>), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors.</p></sec><sec><title>Conclusions/Significance</title><p>There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Weiss, H" uniqKey="Weiss H">H Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corey, L" uniqKey="Corey L">L Corey</name></author><author><name sortKey="Adams, Hg" uniqKey="Adams H">HG Adams</name></author><author><name sortKey="Brown, Za" uniqKey="Brown Z">ZA Brown</name></author><author><name sortKey="Holmes, Kk" uniqKey="Holmes K">KK Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reichman, Rc" uniqKey="Reichman R">RC Reichman</name></author><author><name sortKey="Badger, Gj" uniqKey="Badger G">GJ Badger</name></author><author><name sortKey="Mertz, Gj" uniqKey="Mertz G">GJ Mertz</name></author><author><name 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centrafricaine</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Caroline du Nord</li><li>Gauteng</li><li>Grand Londres</li><li>Île-de-France</li></region><settlement><li>Johannesbourg</li><li>Londres</li><li>Paris</li></settlement><orgName><li>Université du Witwatersrand</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Weiss, Helen A" sort="Weiss, Helen A" uniqKey="Weiss H" first="Helen A." last="Weiss">Helen A. Weiss</name></region><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name><name sortKey="Mayaud, Philippe" sort="Mayaud, Philippe" uniqKey="Mayaud P" first="Philippe" last="Mayaud">Philippe Mayaud</name></country><country name="Guatemala"><noRegion><name sortKey="Paz Bailey, Gabriela" sort="Paz Bailey, Gabriela" uniqKey="Paz Bailey G" first="Gabriela" last="Paz Bailey">Gabriela Paz Bailey</name></noRegion></country><country name="Malawi"><noRegion><name sortKey="Phiri, Sam" sort="Phiri, Sam" uniqKey="Phiri S" first="Sam" last="Phiri">Sam Phiri</name></noRegion></country><country name="République centrafricaine"><noRegion><name sortKey="Gresenguet, Gerard" sort="Gresenguet, Gerard" uniqKey="Gresenguet G" first="Gerard" last="Gresenguet">Gerard Gresenguet</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Legoff, Jerome" sort="Legoff, Jerome" uniqKey="Legoff J" first="Jerome" last="Legoff">Jerome Legoff</name></region><name sortKey="Belec, Laurent" sort="Belec, Laurent" uniqKey="Belec L" first="Laurent" last="Belec">Laurent Belec</name></country><country name="Canada"><noRegion><name sortKey="Pepin, Jacques" sort="Pepin, Jacques" uniqKey="Pepin J" first="Jacques" last="Pepin">Jacques Pepin</name></noRegion></country><country name="Afrique du Sud"><noRegion><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name></noRegion><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name></country><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Hoffman, Irving F" sort="Hoffman, Irving F" uniqKey="Hoffman I" first="Irving F." last="Hoffman">Irving F. Hoffman</name></region><name sortKey="Miller, William C" sort="Miller, William C" uniqKey="Miller W" first="William C." last="Miller">William C. Miller</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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