***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Skin and mucosal herpes simplex virus type 2 ( HSV-2 ) shedding predominantly occurs in short sub clinical episodes . We assessed whether st and ard-dose or high-dose antiviral therapy reduces the frequency of such shedding . METHODS HSV-2-seropositive , HIV-seronegative people were enrolled at the University of Washington Virology Research Clinic ( WA , USA ) . We did three separate but complementary open-label cross-over studies comparing no medication with aciclovir 400 mg twice daily ( st and ard-dose aciclovir ) , valaciclovir 500 mg daily ( st and ard-dose valaciclovir ) with aciclovir 800 mg three times daily ( high-dose aciclovir ) , and st and ard-dose valaciclovir with valaciclovir 1 g three times daily ( high-dose valaciclovir ) . The allocation sequence was generated by a r and om number generator . Study drugs were supplied in identical , numbered , sealed boxes . Study periods lasted 4 - 7 weeks , separated by 1 week wash-out . Participants collected genital swabs four times daily for quantitative HSV DNA PCR . Clinical data were masked from laboratory personnel . The primary endpoint was within-person comparison of shedding rate in each study group . Analysis was per protocol . The trials are registered at Clinical Trials.gov ( NCT00362297 , NCT00723229 , NCT01346475 ) . RESULTS Of 113 participants r and omised , 90 were eligible for analysis of the primary endpoint . Participants collected 23 605 swabs ; 1272 ( 5·4 % ) were HSV-positive . The frequency of HSV shedding was significantly higher in the no medication group ( n=384 , 18·1 % of swabs ) than in the st and ard-dose aciclovir group ( 25 , 1·2 % ; incidence rate ratio [ IRR ] 0·05 , 95 % CI 0·03 - 0·08 ) . High-dose aciclovir was associated with less shedding  than st and ard-dose valaciclovir ( 198 [ 4·2 % ] vs 209 [ 4·5 % ] ; IRR 0·79 , 95 % CI 0·63 - 1·00 ) . Shedding was less frequent in the high-dose valaciclovir group than in the st and ard-dose valaciclovir group ( 164 [ 3·3 % ] vs 292 [ 5·8 % ] ; 0·54 , 0·44 - 0·66 ) . The number of episodes per person-year did not differ significantly for st and ard-dose valaciclovir ( 22·6 ) versus high-dose aciclovir ( 20·2 ; p=0·54 ) , and st and ard-dose valaciclovir ( 14·9 ) versus high-dose valaciclovir ( 16·5 ; p=0·34 ) , but did for no medication ( 28·7 ) and st and ard-dose aciclovir ( 10·0 ; p=0·001 ) . Median episode duration was longer for no medication than for st and ard-dose aciclovir ( 13 h vs 7 h ; p=0·01 ) and for st and ard-dose valaciclovir than for high-dose valaciclovir ( 10 h vs 7 h ; p=0·03 ) , but did not differ significantly between st and ard-dose valaciclovir and high-dose aciclovir ( 8 h vs 8 h ; p=0·23 ) . Likewise , maximum log(10 ) copies of HSV detected per mL was higher for no medication than for st and ard dose aciclovir ( 3·3 vs 2·9 ; p=0·02 ) , and for st and ard-dose valaciclovir than for high-dose valaciclovir ( 2·5 vs 3·0 ; p=0·001 ) , but no significant difference was recorded for st and ard-dose valaciclovir versus high-dose aciclovir ( 2·7 vs 2·8 ; p=0·66 ) . 80 % of episodes were sub clinical in all study groups . Except for a higher frequency of headaches  with high-dose valaciclovir ( n=13 , 30 % ) than with other regimens , all regimens were well tolerated . INTERPRETATION Short bursts of sub clinical genital HSV reactivation are frequent , even during high-dose antiherpes therapy , and probably account for continued transmission of HSV during suppressive antiviral therapy . More potent antiviral therapy is needed to eliminate HSV transmission . FUNDING NIH . Valaciclovir was provided for trial 3 for free by GlaxoSmithKline Summary Herpes simplex virus type 2 ( HSV-2 ) is considered as a major co-factor of both sexual transmission and acquisition of the human immunodeficiency virus ( HIV ) . The HIV epidemic in Senegal is characterized by a remarkable and stable low prevalence . Whether HSV-2 may also constitute a possible co-factor favouring the spreading of HIV epidemic in Senegal is yet unknown . This prompted us to evaluate the HSV-2 seroprevalence in the sentinel population of pregnant women in Senegal . Two hundred and sixty pregnant women attending Roi Baudouin maternity in the capital city Dakar ( n = 135 ) and the antenatal clinic in Kaolack ( n = 125 ) , the third city of Senegal , were prospect ively recruited between March and August 2003 . Fifty-six women ( 22 % ) were positive for HSV-2 serology . The prevalence of HSV-2 seropositivity was higher in women living in Dakar ( 26 % ) than in those living in Kaolack ( 16 % ) ( P < 0.01 ) . Only two women from Dakar and two other from Kaolack were found to be HIV-1-infected . Our observations suggest a seemingly low seroprevalence of HSV-2 infection in adult women Senegal , comparable with those usually reported in Western countries . Further , epidemiological surveys are needed to confirm these results in the general population Background : The epidemiologic utility of STARHS hinges not only on producing accurate estimates of HIV incidence , but also on identifying risk factors for recent HIV infection . Methods : As part of an HIV seroincidence study , 800 Rw and an female sex workers ( FSW ) were HIV tested , with those testing positive further tested by BED-CEIA ( BED ) and AxSYM Avidity Index ( Ax-AI ) assays .  A sample of HIV-negative ( N=397 ) FSW were followed prospect ively for HIV seroconversion . We compared estimates of risk factors for : 1 ) prevalent HIV infection ; 2 ) recently acquired HIV infection ( RI ) based on three different STARHS classifications ( BED alone , Ax-AI alone , BED/Ax-AI combined ) ; and 3 ) prospect ively observed seroconversion . Results : There was mixed agreement in risk factors between methods . HSV-2 coinfection and recent STI treatment were associated with both prevalent HIV infection and all three measures of recent infection . A number of risk factors were associated only with prevalent infection , including widowhood , history of forced sex , regular alcohol consumption , prior imprisonment , and current breastfeeding . Number of sex partners in the last 3 months was associated with recent infection based on BED/Ax-AI combined , but not other STARHS-based recent infection outcomes or prevalent infection . Risk factor estimates for prospect ively observed seroconversion differed in magnitude and direction from those for recent infection via STARHS . Conclusions : Differences in risk factor estimates by each method could reflect true differences in risk factors between the prevalent , recently , or newly infected population s , the effect of study interventions ( among those followed prospect ively ) , or assay misclassification . Similar investigations in other population s/ setting s are needed to further establish the epidemiologic utility of STARHS for identifying risk factors , in addition to incidence rate estimation To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to  HIV-1 acquisition , we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy .  CD4 + and CD8 + T cells and a mixed population of plasmacytoid and myeloid dendritic cells ( DCs ) , including cells expressing the C-type lectin receptor DC-SIGN , persisted at sites of HSV-2 reactivation for months after healing , even with daily antiviral therapy . The CD4 + T cells that persisted reacted to HSV-2 antigen , were enriched for expression of the chemokine receptor CCR5 , and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN . Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies . The persistence and enrichment of HIV receptor – positive inflammatory cells in the genitalia help explain the inability of anti – HSV-2 therapy to reduce HIV acquisition Genital herpes continues to be epidemic throughout most sexually active population s [ 1 - 4 ] . A recent serosurvey indicated that 21.7 % of the U.S. population have HSV-2 antibodies , which represents a 31 % increase in prevalence in the last decade [ 5 , 6 ] . The seroprevalence of HSV-2 averages 30 % in most family practice and obstetrics clinics and 30 % to 50 % among sexually transmitted disease clinic attendees . Seroprevalence is consistently higher in women than in men [ 7 , 8 ] . The natural history of HSV infection includes acute or sub clinical first-episode mucocutaneous infection , establishment of neuronal latency , and intermittent virus reactivation with or without associated recurrent symptoms [ 9 , 10 ] . Although this sequence of events has been recognized for more than five decades , little is known about the long-term natural history of genital herpes . In the late 1970s , supported by the National Institutes of Health , we began a prospect i ve study of a large cohort of persons with recently acquired symptomatic genital HSV infection in order to define more precisely the natural history of genital herpes . Clinical , demographic , and recurrence data were collected for 457 patients who presented with virologically , serologically , and clinical ly confirmed first-episode genital infection . More than half of these patients did not receive antiviral therapy during their primary episode , providing a population not likely to be replicated in the future . We summarize the natural history of symptomatic recurrences in the complete population and in the subset of untreated patients . Methods In 1974 , a research clinic dedicated to the study of genital herpes infection was established at Harborview Medical Center , a King Countyfunded hospital affiliated with the University of Washington . Patients were referred by their private physicians or by the sexually transmitted disease clinic at Harborview , or responded to advertisements for participation in clinical studies of HSV infection . Only patients willing to participate in prospect i ve studies with long-term follow-up or in therapeutic trials were enrolled . Between 1974 and 1988 , we registered 457 patients with serologically and virologically proven first-episode infection who were followed for at least 60 days from the onset of infection . At the initial clinic visit , genital lesions were cultured and described by anatomic site , stage , and area . Patients were then generally followed at 2- to 3-day intervals until their lesions had healed . The median number of visits and genital examinations during the initial disease episode was 5 ( range , 3 to 14 visits ) . After resolution of the first clinical episode , patients were instructed to return to the clinic during each recurrence or for routine visits at least every 2 to 3 months . Patients who were unable to return for each recurrence were instructed to maintain a diary of onset and resolution date s for each recurrence . These data were collected at the following clinic visit . In general , we insisted that patients return for recurrences until they were able to recognize the signs and symptoms of genital herpes reactivation and to fill out patient diaries about onset and healing of reactivations . We defined a recurrence of genital herpes as the presence of genital ulcerations . We defined duration of a recurrence as the number of days from the first appearance of genital lesions to the reepithelialization of all lesions . If new lesions appeared before complete healing of other lesions , all were considered part of the same episode . We report only recognized symptomatic ( lesional ) recurrences and do not address sub clinical shedding of HSV in the genital tract . Serum specimens from both the acute and convalescent phases were obtained from all patients and tested for HSV-specific antibodies by Western blot ; all patients showed seroconversion to HSV-1 or HSV-2 [ 11 , 12 ] . Some had antibodies to HSV-1 in their acute-phase specimen and antibodies to both HSV-1 and HSV-2 in their convalescent-phase specimens . Patients were categorized as having primary first-episode disease if their acute-phase serum specimen showed absence of antibodies to HSV by Western blot . Based on Western blot profiles of convalescent-phase specimens and the subtype of the 
    Output:
    
Interpretation A large burden of HIV is likely to be attributable to HSV-2 infection , even if the effect of HSV-2 infection on HIV had been imperfectly measured in studies providing adjusted RR estimates , potentially because of residual confounding .
The contribution is likely to be greatest in areas where HSV-2 is highly prevalent , particularly Africa .
New preventive interventions against HSV-2 infection could not only improve the quality of life of millions of people by reducing the prevalence of herpetic genital ulcer disease , but could also have an additional , indirect effect on HIV transmission .