***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: A r and omized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy ( valacyclovir , 500 mg twice daily , or placebo for 8 weeks , a 2-week washout period , then the alternative therapy for 8 weeks ) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 ( HIV-1 ) who were not on antiretroviral therapy .  Plasma sample s ( obtained weekly ) and endocervical swab specimens ( obtained thrice weekly ) were collected for HIV-1 RNA polymerase chain reaction . Plasma HIV-1 level was significantly lower during the valacyclovir arm , compared with the placebo arm ( -0.26 log10 copies/mL , a 45 % decrease [ P < .001 ] ) , as was cervical HIV-1 level ( -0.35 log10 copies/swab , a 55 % decrease [ P < .001 ] ) . Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression BACKGROUND Epidemiologic data suggest that infection with herpes simplex virus type 2 ( HSV-2 ) is associated with increased genital shedding of human immunodeficiency virus type 1 ( HIV-1 ) RNA and HIV-1 transmissibility . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of HSV suppressive therapy with valacyclovir ( at a dose of 500 mg twice daily ) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2 ; all were ineligible for highly active antiretroviral therapy . The patients were followed for 24 weeks ( 12 weeks before and 12 weeks after r and omization ) . Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment , adjusting for baseline values , and to evaluate the effect over time . RESULTS A total of 140 women were r and omly assigned to treatment groups ; 136 were included in the analyses . At enrollment , the median CD4 cell count was 446 cells per cubic millimeter , and the mean plasma viral load was 4.44 log10 copies per milliliter . With the use of summary - measures analysis , valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA ( odds ratio , 0.41 ; 95 % confidence interval [ CI ] , 0.21 to 0.80 ) and in the mean quantity of the virus ( log(10 ) copies per milliliter , -0.29 ; 95 % CI , -0.44 to -0.15 ) . However , there was no significant decrease in detection of HIV ( risk ratio , 0.93 ; 95 % CI , 0.81 to 1.07 ) . HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log(10 ) copy per milliliter ( 95 % CI , -0.72 to -0.35 ) . Repeated- measures analysis showed that these effects became significantly stronger during the 3 months of follow-up . CONCLUSIONS HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women . This finding may have important implication s for HIV control . ( Clinical Trials.gov number , NCT00158509 [ Clinical Trials.gov ] . ) BACKGROUND Herpes simplex virus ( HSV ) suppressive therapy reduces genital and plasma human immunodeficiency virus type 1 ( HIV-1 ) RNA over periods up to 3 months , but the long-term effect is unknown . METHODS A total of 484 HIV-1 and HSV type 2 seropositive Tanzanian women aged 16 - 35 years were enrolled in a r and omized placebo-controlled trial of acyclovir administered at a dosage of 400 mg twice daily . Cervico-vaginal lavage and blood sample s were collected at 6 months , 12 months , and 24 months for quantification of genital and plasma HIV-1 RNA and genital HSV DNA . Primary outcomes were detection and quantity of cervico-vaginal HIV-1 RNA at 6 months . RESULTS At 6 months , there was little difference between the acyclovir and placebo arms for cervico-vaginal HIV-1 RNA detection ( 88 [ 41 .3 % ] of 213 vs 84 [ 44 .0 % ] of 191 ; odds ratio [ OR ] , 0.90 ; 95 % confidence interval [ CI ] , 0.60 - 1.33 ) , HSV DNA detection ( 20 [ 9 .4 % ] of 213 vs 22 [ 11 .5 % ] of 191 ; OR , 0.80 ; 95 % CI , 0.42 - 1.51 ) , genital HIV or HSV loads , or plasma HIV-1 RNA load . Estimated median adherence was 91 % . There was a suggestion of an impact on cervico-vaginal HIV-1 RNA detection among women with estimated adherence 90 % ( OR , 0.74 ; 95 % CI , 0.50 - 1.09 ) when data from all 3 visits were included . CONCLUSIONS Acyclovir administered at a dosage of 400 mg twice daily is unlikely to be a useful long-term intervention to reduce HIV transmission . The lack of effect on HIV may be attributable to suboptimal adherence or treatment regimen Genital HIV-1 RNA quantity predicts risk of heterosexual HIV-1 transmission independently of plasma HIV-1 concentration . Elucidating the Insidious Transmission of a Deadly Pathogen The deadly HIV-1 retrovirus that causes AIDS has been a scourge of humanity for nearly 30 years . Although combination therapy with antiretroviral drugs has proved successful , the complex drug regimen and great cost have prevented their widespread use in the developing world where they are most needed . The goal of developing a vaccine that would protect individuals from becoming infected with HIV-1 has remained elusive . Given that 90 % of all HIV infections worldwide are due to sexual transmission , there has been much interest in developing new strategies that could block HIV infection through the genital mucosa . However , the mechanisms underlying mucosal transmission of HIV are still poorly understood . Higher amounts of HIV-1 in genital secretions are thought to reflect a greater chance of sexual transmission , but testing this correlation is a difficult undertaking . Baeten and colleagues have taken on this challenge with their prospect i ve study in Africa of 2521 heterosexual serodiscordant couples ( one partner is HIV-infected and the other partner is not ) . These investigators evaluated the relationship between the quantity of HIV-1 RNA in the genital secretions of the infected partner and the risk of HIV-1 transmission to the uninfected partner in each couple . They tested the amount of HIV-1 RNA in endocervical swabs from 1805 HIV-1–infected women including 46 women known to have transmitted the virus to their male partners . They also tested the amount of HIV-1 RNA  in semen from 716 men , including 32 who had transmitted HIV-1 to their female partners . The authors demonstrate that higher concentrations of HIV-1 RNA in genital secretions are associated with a greater risk of heterosexual transmission of HIV-1 , and that these concentrations provide a new biomarker for predicting the infectiousness of HIV-1–infected individuals . The authors propose that HIV-1 RNA concentrations in genital secretions could also be used as a biomarker to monitor the efficacy of new microbicides and other interventions design ed to block mucosal transmission of the virus . High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission . Although plasma and genital HIV-1 RNA concentrations are correlated , no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission . In a prospect i ve study of 2521 African HIV-1 serodiscordant couples , we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk . HIV-1 transmission linkage was established within the partnership by viral sequence analysis . We tested endocervical sample s from 1805 women , including 46 who transmitted HIV-1 to their partner , and semen sample s from 716 men , including 32 who transmitted HIV-1 to their partner . There was a correlation between genital and plasma HIV-1 RNA concentrations : For endocervical swabs , Spearman ’s rank correlation coefficient ρ was 0.56 , and for semen , ρ was 0.55 . Each 1.0 log10 increase in genital HIV-1 RNA was associated with a 2.20-fold ( for endocervical swabs : 95 % confidence interval , 1.60 to 3.04 ) and a 1.79-fold ( for semen : 95 % confidence interval , 1.30 to 2.47 ) increased risk of HIV-1 transmission . Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity ( hazard ratio , 1.67 for endocervical swabs and 1.68 for semen ) . Seven female-to-male and four male-to-female HIV-1 transmissions ( incidence < 1 % per year ) occurred from persons with undetectable genital HIV-1 RNA , but in all 11 cases , plasma HIV-1 RNA was detected . Thus , higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission , and this effect was independent of plasma HIV-1 concentrations . These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk 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 Background Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection . The validity of these findings has been question ed because of their retrospective design , diverse study population s , variable compliance with anti-tuberculous therapy and use of anti-retroviral medication . To assess the impact of tuberculosis on survival in HIV infection we performed a prospect i ve study among HIV-infected Ug and an adults with and without tuberculosis . Methods In a prospect i ve cohort study , 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival . To assess changes in viral load over 1 year , 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count , age , sex and tuberculin skin test status . Results During the follow-up period , 63 out of of 230 tuberculosis cases ( 28 % ) died compared with 85 out of 442 controls ( 19 % ) , with a crude risk ratio of 1.4 [ 95 % confidence interval ( CI ) , 1.07–1.87 ] . Most deaths occurred in patients with CD4 lymphocyte counts < 200 × 106 cells/l at baseline ( n = 99 ) and occurred with similar frequency in the tuberculosis cases ( 46 % ) and the controls ( 44 % ) . When the CD4 lymphocyte count was > 200 × 106 /l , however , the relative risk of death in HIV-associated tuberculosis was 2.1 ( 95 % CI , 1.27–3.62 ) compared with subjects without tuberculosis . For subjects with a CD4 lymphocyte count > 200 × 106/l , the 1-year survival proportion was slightly lower in the cases than in the controls ( 0.91 versus 0.96 ) , but by 2 years the survival proportion was significantly lower in the cases than in the controls ( 0.84 versus 0.91;P < 0.02 ; log-rank test ) . For subjects with a CD4 lymphocyte count of 200 × 106 cells/l or fewer , the survival proportion at 1 year for the controls was lower than cases ( 0.59 versus 0.64 
    Output:
    
Coinfections may increase HIV viral load in population s where they are prevalent , thereby facilitating HIV transmission .
These effects may be reversed with treatment .