Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe

Brown, Joelle; Wald, Anna; Hubbard, Alan; Rungruengthanakit, Kittipong; Chipato, Tsungai; Rugpao, Sungwal; Mmiro, Francis; Celentano, David D.; Salata, Robert; Morrison, Charles; Richardson, Barbra A.; Padian, Nancy

doi:10.1097/qad.0b013e3282004929

Cited by 93 publications

(73 citation statements)

References 39 publications

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“…Prevalent HSV-2 infection has been associated with increased risk of HIV acquisition and transmission 36 and has been cited as a potential driving force of the epidemic in Uganda 37,38 and elsewhere in Africa. 39 Most behavioral interventions focused on preventing HIV infection should theoretically also prevent HSV-2.…”

Section: Commentmentioning

confidence: 99%

Risk Factors for Recent HIV Infection in Uganda

Mermin

Musinguzi²,

Opio³

et al. 2008

JAMA

115

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Context Studies of factors associated with acquiring human immunodeficiency virus (HIV) are often based on prevalence data that might not reflect recent infections. Objective To determine demographic, biological, and behavioral factors for recent HIV infection in Uganda. Design and Setting Nationally representative household survey of cross-sectional design conducted in Uganda from August 2004 through January 2005; data were analyzed until November 2007.Participants There were 11 454 women and 9905 men aged 15 to 59 years who were eligible. Questionnaires were completed for 10 826 women (95%) and 8830 men (89%); of those interviewed, blood specimens were collected for 10 227 women (94%) and 8298 men (94%).Main Outcome Measure Specimens seropositive for HIV were tested with the BED IgG capture-based enzyme immunosorbent assay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments. ResultsOf the 1023 HIV infections with BED results, 172 (17%) tested as recent. In multivariate analysis, risk factors associated with recent HIV infection included female sex (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.1-5.2); current marital status (widowed vs never married, aOR, 6.1; 95% CI, 2.8-13.3; divorced vs never married, aOR, 3.0; 95% CI, 1.5-6.1); geographic region (north central Uganda vs central Uganda/Kampala, aOR, 2.6; 95% CI, 1.7-4.1); number of sex partners in past year (Ն2 compared with none; aOR, 2.9; 95% CI, 1.6-5.5); herpes simplex virus type 2 infection (aOR, 3.9; 95% CI, 2.6-5.8); report of a sexually transmitted disease in the past year (aOR, 1.7; 95% CI, 1.2-2.4); and being an uncircumcised man (aOR, 2.5; 95% CI, 1.1-5.3). Among married participants, recent HIV infection was associated with never using condoms with partners outside of marriage (aOR, 3.2; 95% CI, 1.7-6.1) compared with individuals having no outside partners. The risk of incident HIV infection for married individuals who used condoms with at least 1 outside partner was similar to that of those who did not have any partners outside of marriage (aOR, 1.0; 95% CI, 0.3-2.7). ConclusionA survey of individuals in Uganda who were tested with an HIV assay used to establish recent infection identified risk factors, which offers opportunities for prevention initiatives.

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Section: Commentmentioning

confidence: 99%

Risk Factors for Recent HIV Infection in Uganda

Mermin

Musinguzi²,

Opio³

et al. 2008

JAMA

115

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“…In addition to genital herpes, transmission of HSV-2 to neonates causes severe life-threatening infections [3]. Recent studies suggest a link between genital herpes and increased rates of transmission [4,5] and elevated viral loads [6] of human immunodeficiency virus (HIV). Therefore, an effective HSV-2 vaccine is needed.…”

Section: Introductionmentioning

confidence: 99%

Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs

Hoshino

Pesnicak

Dowdell

et al. 2008

Vaccine

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A replication-defective HSV-2 vaccine, dl5-29, which is deleted for two essential early genes, UL5 and UL29, is highly immunogenic and protective in mice and guinea pigs. In a prior study, a derivative of HSV-2 dl5-29 termed dl5-29-41L, which has an additional deletion in UL41 (that encodes the virion-host shut-off protein), was more immunogenic and protective against challenge with wildtype HSV-2 in mice when compared with dl5-29. To determine if deletion of UL41 improves the efficacy of dl5-29 in protecting guinea pigs from HSV-2, animals were immunized with dl5-29, dl5-29-41L, or PBS. The geometric mean neutralizing antibody titers from the dl5-29 and dl5-29-41L recipients were comparable (10 1.97 and 10 2.19 , respectively, p=0.15). After intravaginal challenge with wild-type HSV-2, the dl5-29-41L and dl5-29 recipients shed similar titers of HSV-2 from the vagina. Mean acute disease severity scores, numbers of recurrences during 3 months after infection, and latent viral loads in sacral ganglia were similar for dl5-29 and dl5-29-41L (all p values >0.05). dl5-29 and dl5-29-41L completely protected mice from lethal challenge with HSV-2 and induced virus-specific CD8 + T cells in the spleens of the animals. Thus, dl5-29 was as immunogenic and protective as dl5-29-41L under these conditions. dl5-29 was at least 250,000-fold less virulent than parental virus by intracranial inoculation in healthy mice, and caused no disease in SCID mice. Both dl5-29-41L and dl5-29 are equally effective and immunogenic in guinea pigs, and dl5-29 is very safe in immunocompromised animals.

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“…In a prospective cohort study involving 4531 women from Uganda and Zimbabwe, the risk of HIV-1 acquisition was higher in those who acquired HSV-2 infection during the study (HR 4.6; 95% CI, 1.6-13.1 in Uganda and HR 8.6; 95% CI, 4.3-17.1 in Zimbabwe) than in those who were HSV-2 seropositive at baseline (HR 2.8; 95% CI, 1. 5-5.3 in Uganda and HR 4.4; 95% CI, 2.7-7.2 in Zimbabwe), after adjustment for confounding [13]. This increased risk may be explained by the more severe lesions associated with primary genital herpes infections, the subsequent more frequent recurrences in the fi rst year of infection, and the higher rates of subclinical reactivation of HSV-2 in early versus more chronic HSV-2 infection.…”

Section: Hsv-2 Infection and Hiv-1 Acquisitionmentioning

confidence: 82%

New insights on interactions between HIV-1 and HSV-2

Delany‐Moretlwe

Lingappa²,

Celum³

2009

Curr Infect Dis Rep

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Herpes simplex type 2 (HSV-2) infection is common and frequently asymptomatic. Concerns exist about the high prevalence of HSV-2, particularly in areas of high HIV prevalence, because of observations that HSV-2 is associated with an increased risk of HIV acquisition, transmission, and disease progression. Several randomized trials have tested or are testing whether HSV-2 treatment can limit the spread of HIV, with mixed results. Although treatment with acyclovir, 400 mg twice daily, does not reduce HIV incidence, suppressive acyclovir and valacyclovir reduce HIV levels in plasma and in the genital tract. Ongoing trials are evaluating whether HSV suppression will reduce HIV transmission and disease progression. Until a protective HSV-2 or HIV vaccine is available, effective interventions that reduce the effect of HSV-2 on HIV transmission are critically needed.

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Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe

Abstract: HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

Cited by 93 publications

References 39 publications

Risk Factors for Recent HIV Infection in Uganda

Risk Factors for Recent HIV Infection in Uganda

Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs

New insights on interactions between HIV-1 and HSV-2

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