Wednesday, October 5, 2022

How Does Hsv 2 Increase Risk Of Hiv

How Do People Get Genital Herpes

Breakthrough treatment cures 3rd patient of HIV | ABCNL

Infections are transmitted through contact with HSV in herpes lesions, mucosal surfaces, genital secretions, or oral secretions. 5 HSV-1 and HSV-2 can be shed from normal-appearing oral or genital mucosa or skin. 7,8 Generally, a person can only get HSV-2 infection during genital contact with someone who has a genital HSV-2 infection. However, receiving oral sex from a person with an oral HSV-1 infection can result in getting a genital HSV-1 infection. 4 Transmission commonly occurs from contact with an infected partner who does not have visible lesions and who may not know that he or she is infected. 7 In persons with asymptomatic HSV-2 infections, genital HSV shedding occurs on 10.2% of days, compared to 20.1% of days among those with symptomatic infections. 8

Specimen Collection And Laboratory Tests

Blood specimen was collected in two vacutainer tubes . An aliquot of the Plasma was used for the HIV testing at enrolment visit. This was done using Sequential Rapid test kits: DETERMINE – Abbot Laboratories, 100 Abbot Park, IL 60064 United States, UNIGOLD – Trinity Biotech Plc, Bray, Ireland. In cases of serial discrepant Rapid HIV Test Results, these results were resolved using a Tie-Breaker STATPAK – Chembio diagnostics Systems, Inc. Medford, N.Y. 11763 USA. All the HIV negative plasma samples were stored immediately at -80 â and later pooled for the detection of HIV RNA using ROCHE- TAQMAN system – Roche diagnostics Corporation 9115 Hague Road, Indianapolis, Indiana 46250 USA.

The women that were confirmed HIV positive were called back during their next antenatal care visit and had their blood drawn for CD4 cells count. This was measured with a Flow cytometer – Partec Inc, 603 Heron Drive unit 9, Swedesborg, NJ 08085 USA.

For the HSV-2, serum was stored at -80 â. The stored serum samples from the date of enrolment were identified for the cohort study, approximately 10ul of this stored serum was used for the HSV-2 testing. The remaining sample was stored back in the -80 â freezer for further testing.

The Enhanced Hiv Infection In Dcs Conditioned With Hsv

Figure 9. STING pathway activation in the dual infected DCs decreased protein levels of several HIV restriction factors. Dendritic cells were exposed to free HSV-2 or complement opsonized virus for 2 h then infected with HIV or complement opsonized HIV for 22 h. Heat map from the RNA seq transcriptome data of intracellular sensors significantly up or down regulated in one or several of the HIV, CHIV, HSV/HIV, or CHSV/CHIV infection conditions compared to mock treated DCs. The levels of SAMHD1, ABOBEC3G, and TREX1 in the DCs from the different infection conditions were assessed by staining the cells and analyzed by flow cytometry. cGAMP was given exogenously or delivered intracellularly via DOTAP to the DCs, following this were the DCs left unexposed or exposed to together with HIV for 16 h. In addition, one group of DCs were exposed to HSV for 2 h followed by HIV or CHIV for 16 h. The levels of SAMHD1, ABOBEC3G, and TREX1 were assessed by staining the cells and analyzed by flow cytometry. *p< 0.05 **p< 0.005 ***p< 0.0005. N = 58.

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Generation Of Gfp Reporter Ccr5

NLENG1-IRES proviral construct was used to generate NLENG1-IRES-70 by replacing ENV with YU-2 ENV as described elsewhere . The proviral construct was generously donated by Dr. David N Levy . HEK-293T cells were cultured in DMEM containing 10% HI FCS, and at ~70% confluency, the cells were transfected with NLENG1-IRES-70 proviral construct using the CaPO4 method. After 8 h of transfection, the media was replaced with DMEM supplemented with 1% HI FCS. The GFP-HIV was harvested the next day by collecting supernatant, and cell debris were removed by pelleting at 2,500 rpm for 5 min. Virus stocks were aliquoted and frozen at 80°C.

How Common Is Genital Herpes

STDs: Causes and Risk Factors

Genital herpes infection is common in the United States. CDC estimated that there were 572,000 new genital herpes infections in the United States in a single year.1 Nationwide, 11.9 % of persons aged 14 to 49 years have HSV-2 infection .2 However, the prevalence of genital herpes infection is higher than that because an increasing number of genital herpes infections are caused by HSV-1. 3 Oral HSV-1 infection is typically acquired in childhood because the prevalence of oral HSV-1 infection has declined in recent decades, people may have become more susceptible to contracting a genital herpes infection from HSV-1. 4

HSV-2 infection is more common among women than among men the percentages of those infected during 2015-2016 were 15.9% versus 8.2% respectively, among 14 to 49 year olds. 2 This is possibly because genital infection is more easily transmitted from men to women than from women to men during penile-vaginal sex. 5 HSV-2 infection is more common among non-Hispanic blacks than among non-Hispanic whites . 2 A previous analysis found that these disparities, exist even among persons with similar numbers of lifetime sexual partners. Most infected persons may be unaware of their infection in the United States, an estimated 87.4% of 14 to 49 year olds infected with HSV-2 have never received a clinical diagnosis. 6

The age-adjusted percentage of persons in the United States infected with HSV-2 decreased from 18.0% in 19992000 to 12.1% in 2015-2016. 2

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Scientists Learn Why Even Treated Genital Herpes Sores Boost The Risk Of Hiv Infection

New research helps explain why infection with herpes simplex virus-2 , which causes genital herpes, increases the risk for HIV infection even after successful treatment heals the genital skin sores and breaks that often result from HSV-2.

Scientists have uncovered details of an immune-cell environment conducive to HIV infection that persists at the location of HSV-2 genital skin lesions long after they have been treated with oral doses of the drug acyclovir and have healed and the skin appears normal. These findings are published in the advance online edition of Nature Medicine on Aug. 2.

Led by Lawrence Corey, M.D., and Jia Zhu, Ph.D., of the Fred Hutchinson Cancer Research Center and Anna Wald, M.D., M.P.H., of the University of Washington, both in Seattle, the study was funded mainly by the National Institute of Allergy and Infectious Diseases with support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, both part of the National Institutes of Health.

“The findings of this study mark an important step toward understanding why HSV-2 infection increases the risk of acquiring HIV and why acyclovir treatment does not reduce that risk,” says NIAID Director Anthony S. Fauci, M.D. “Understanding that even treated HSV-2 infections provide a cellular environment conducive to HIV infection suggests new directions for HIV prevention research, including more powerful anti-HSV therapies and ideally an HSV-2 vaccine.”

Special Considerations With Regard To Starting Antiretroviral Therapy

Orolabial and genital HSV should not influence the decision on when to start ART in persons with HIV. Transient increases in HSV-2âassociated genital ulcers have been observed during the first 6 months after initiation of ART in HIV/HSV-2 coinfected persons. In such cases, suppressive anti-HSV therapy can be considered. The frequency and severity of clinical episodes of genital herpes is often reduced in individuals after immune reconstitution on ART. However, immune reconstitution does not reduce the frequency of genital HSV shedding.33

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Suppressive Therapy For Recurrent Hsv

Suppressive therapy reduces frequency of genital herpes recurrences by 70%80% among patients who have frequent recurrences . Persons receiving such therapy often report having experienced no symptomatic outbreaks. Suppressive therapy also is effective for patients with less frequent recurrences. Long-term safety and efficacy have been documented among patients receiving daily acyclovir, valacyclovir, and famciclovir . Quality of life is improved for many patients with frequent recurrences who receive suppressive therapy rather than episodic treatment . Providers should discuss with patients on an annual basis whether they want to continue suppressive therapy because frequency of genital HSV-2 recurrence diminishes over time for many persons. However, neither treatment discontinuation nor laboratory monitoring is necessary because adverse events and development of HSV antiviral resistance related to long-term antiviral use are uncommon.

Valacyclovir 500 mg orally 2 times/day for 3 daysOR

Valacyclovir 1 gm orally once daily for 5 days

*Acyclovir 400 mg orally 3 times/day is also effective, but are not recommended because of frequency of dosing.

How Can Herpes Be Prevented

HIV & AIDS – signs, symptoms, transmission, causes & pathology

Correct and consistent use of latex condoms can reduce, but not eliminate, the risk of transmitting or acquiring genital herpes because herpes virus shedding can occur in areas that are not covered by a condom.25,26

The surest way to avoid transmission of STDs, including genital herpes, is to abstain from sexual contact, or to be in a long-term mutually monogamous relationship with a partner who has been tested for STDs and is known to be uninfected.

Persons with herpes should abstain from sexual activity with partners when herpes lesions or other symptoms of herpes are present. It is important to know that even if a person does not have any symptoms, he or she can still infect sex partners. Sex partners of infected persons should be advised that they may become infected and they should use condoms to reduce the risk. Sex partners can seek testing to determine if they are infected with HSV.

Daily treatment with valacyclovir decreases the rate of HSV-2 transmission in discordant, heterosexual couples in which the source partner has a history of genital HSV-2 infection. 27 Such couples should be encouraged to consider suppressive antiviral therapy as part of a strategy to prevent transmission, in addition to consistent condom use and avoidance of sexual activity during recurrences.

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Monitoring Of Response To Therapy And Adverse Events

Acyclovir, valacyclovir, and famciclovir are occasionally associated with nausea or headache. No laboratory monitoring is needed for patients receiving episodic or suppressive HSV therapy unless they have advanced renal impairment. However, for patients receiving high-dose IV acyclovir, monitoring of renal function, and dose adjustment as necessary, are recommended at initiation of treatment and once or twice weekly for the duration of treatment.

HSV-2 shedding and GUD can increase in the first 6 months after initiation of ART, particularly in those with low CD4 counts.34,35 Mucocutaneous lesions that are atypical and occasionally recalcitrant to therapy have been reported in individuals initiating ART and have been attributed to immune reconstitution inflammatory syndrome .36

How Can I Prevent Genital Herpes

If you are sexually active, you can do the following things to lower your chances of getting genital herpes:

  • Being in a long-term mutually monogamous relationship with a partner who does not have herpes.
  • Using condoms the right way every time you have sex.

Be aware that not all herpes sores occur in areas that a condom can cover. Also, the skin can release the virus from areas that do not have a visible herpes sore. For these reasons, condoms may not fully protect you from getting herpes.

If your sex partner has/have genital herpes, you can lower your risk of getting it if:

  • Your partner takes an anti-herpes medicine every day. This is something your partner should discuss with his or her healthcare provider.

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How Do I Get Tested

Thats simple. If you are experiencing symptoms, speak to your doctor or visit your local sexual health centre to test for herpes. The doctor will need to do a swab of the blisters or sores and usually offer a complete STI screen. If your test returns a positive diagnosis it is important to seek treatment immediately.

Genital Herpes During Pregnancy

Acyclovir and Transmission of HIV

Prevention of neonatal herpes depends both on preventing acquisition of genital herpes during late pregnancy and avoiding exposure of the neonate to herpetic lesions and viral shedding during delivery. Mothers of newborns who acquire neonatal herpes often lack histories of clinically evident genital herpes . The risk for transmission to the neonate from an infected mother is high among women who acquire genital herpes near the time of delivery and low among women with prenatal histories of recurrent herpes or who acquire genital herpes during the first half of pregnancy . Women who acquire HSV in the second half of pregnancy should be managed in consultation with maternal-fetal medicine and infectious disease specialists.

All pregnant women should be asked whether they have a history of genital herpes or genital symptoms concerning for HSV infection. At the onset of labor, all women should be questioned thoroughly about symptoms of genital herpes, including prodromal symptoms , and all women should be examined thoroughly for herpetic lesions. Women without symptoms or signs of genital herpes or its prodrome can deliver vaginally. Although cesarean delivery does not eliminate the risk for HSV transmission to the neonate , women with recurrent genital herpetic lesions at the onset of labor should have a cesarean delivery to reduce the risk for neonatal HSV infection.

Acyclovir 400 mg orally 3 times/dayORValacyclovir 500 mg orally 2 times/day

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How The Study Worked

This study involved members of the REACH study group who were HIV-negative or were infected with HIV through risky behavior, usually sex. Researchers tested blood samples for HSV-2 when these young people entered the study and again at the end of the study. They also tested blood samples for HIV when teens entered the study and then every 6 months. The analysis did not include anyone who became infected with HIV during the study period.

The researchers used standard statistical methods to identify risk factors for HSV-2 infection by comparing three groups:

  • Teens positive for HSV-2 versus negative for HSV-2 when they entered the study
  • Teens who became HSV-2-positive during the study versus teens who did not become HSV-2 positive
  • HIV-positive teens who became HSV-2-positive during the study versus HIV-positive teens who did not become HSV-2 positive

Distinct Cellular Programming Was Induced In Dcs By The Different Hiv And Hsv

Figure 2. Cellular programing of dendritic cells by HIV single and HIV/HSV dual infection. Dendritic cells were exposed to HSV-2 or complement opsonized virus for 2 h then infected with HIV or complement opsonized HIV for 24 h. Whole transcriptome sequencing was performed. Analyzes of amount of significantly upregulated or down regulated genes assessing total, two-, four-, and eight-fold changes compared to mock Gene enrichment analysis of genes significantly upregulated three-fold or higher with p 0.05 with focus on inflammatory and antiviral pathways/factors. Gene enrichment analysis of genes significantly upregulated three-fold or higher with p 0.05. GO enrichment analysis was done with PANTHER pathways data set. Terms with statistical significance in any of gene list are shown as stacked bar graph. *p< 0.05, **p< 0.005, ***p< 0.0005. Y-axis = number of listed genes involving in indicated PANTHER pathway. Ref = expected gene number from reference . N = 5.

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Hiv/hsv Exposure Induced Higher Expression Of Several Antiviral Factors Including Ifn

Figure 4. Antiviral factors and pathways were highly activated in HSV/HIV exposed dendritic cells. Dendritic cells were exposed to HSV-2 or complement opsonized virus for 2 h followed by HIV or complement opsonized HIV infection for 22 h. Heat map from RNA seq data of antiviral factors significantly up or down regulated in one or several of the HIV, CHIV, HSV-2/HIV, or CHSV-2/CHIV infection conditions compared to mock treated DCs mRNA expression levels of IFN-, and MXA were accessed by PCR. Data were normalized to mock set as 1. Levels of secreted IFN- were evaluated by ELISA. Level of STAT1 phosphorylation was assessed in lysates from DCs exposed to HSV-2 or CHSV-2 for 2 h followed by HIV or CHIV exposure for 4 h by phosphoprotein bead array. *p< 0.05 **p< 0.005 ***p< 0.0005. N = 58.

Hsv Infection And Symptoms

Gene editing for cure of persistent viral infections

Most individuals infected with HSV have either no symptoms or mild symptoms that go unnoticed. When symptoms do appear, they initially present with tingling and/or redness, followed by blister-like lesions that rapidly merge into open, weeping sores. The sores are often quite painful and can be accompanied by a fever and swollen lymph glands.

Both oral and genital herpes cycle between periods of active disease, which can last from two days to three weeks, followed by a period of remission. After the initial infection, the viruses attach themselves to sensory nerve cells, where they remain for a lifetime. HSV can reactivate at any time , although the frequency and severity of outbreaks tend to subside over time.

Diagnosis is generally made by clinical examination of the patient, although genital herpes is often difficult to diagnose as symptoms can be mild and easily confused with other conditions . Laboratory tests are sometimes used to make a definitive diagnosis, including newer generation HSV antibody tests which can identify HSV-1 or HSV-2 with greater than 98% specificity, but cannot detect new infections, as antibodies to the virus have not yet been made.

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Herpes & Hiv: Not What You Think

It is always a shock to find out that what you had assumed was true simply is not. That is why clinical trials are so important to science. The unexpected results of a recent trial examining herpes and HIV demonstrates the importance of carrying out controlled trials to test preconceived beliefs.

Up to 90% of women with HIV infection in southern Africa also have genital herpes . Most people who are infected with HSV-2 do not know that they have the virus, which causes symptomatic genital sores and breaks in the skin but is frequently active without symptoms. Multiple studies had shown that infection with herpes was associated with an increased risk for HIV infection. However, whether treatment to suppress HSV-2 would decrease HIV transmission had not been tested.

The Partners in Prevention HSV/HIV Transmission Study, led by the University of Washington and funded by the Bill & Melinda Gates Foundation, looked at whether the use of acyclovir, a drug widely used for the safe and effective suppression of HSV-2, by persons who are infected with both HSV-2 and HIV could reduce the likelihood that they would transmit HIV to their HIV-uninfected partners.

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