HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding

HIV Infections Clinical Trial

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Official title:

HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00530777
• Other study ID #: 32462
• Secondary ID: 07-7306-A01R03HD
• Status: Completed
• Phase: Phase 2
• Start date: April 2008
• Est. completion date: August 2010

Study information

• Verified date: November 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, we will determine whether treating pregnant and breastfeeding women co-infected with human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) with daily valacyclovir will reduce HIV-1 levels in plasma, genital, and breast milk and will decrease the risk of mother-to-child HIV-1 transmission (MTCT).

Description:

Each year over 500,000 children become HIV-1-infected in sub-Saharan Africa after exposure to maternal virus in blood, genital secretions, and breast milk. Identifying feasible, safe, and affordable interventions that prevent mother-to-child transmission remains a priority for HIV-1 prevention research. Interventions to reduce breast milk HIV-1 transmission are lacking and most urgently needed.

We propose a randomized clinical trial to determine whether incorporating HSV-2 suppression with valacyclovir into standard prevention of mother-to-child HIV-1 transmission regimens will reduce plasma, cervical, and breast milk HIV-1 RNA levels and risk of transmission among HIV-1-infected and HSV-2-seropositive women. We plan to enroll a total of 148 HIV-1 and HSV-2 co-infected pregnant women with CD4>200 cells/μl who seek antenatal care prior to 32 weeks gestation at a clinic in Nairobi, Kenya. Women will be randomized to receive either valacyclovir suppressive therapy or placebo at 34 weeks gestation and mother-infant pairs will be followed for 12 months postpartum. Follow-up visits will be scheduled at 38 weeks gestation; birth; 2, 6, 10 and 14 weeks; and 6, 9, and 12 months postpartum. Maternal blood, genital, and breast milk specimens obtained at follow-up visits will be used to determine the effect of valacyclovir suppressive therapy on plasma and breast milk HIV-1 RNA levels. Infant filter paper specimens for HIV-1 DNA assays will be collected at birth; 2, 6, 10 and 14 weeks; and 6, 9, and 12 months in order to compare the proportion of infants acquiring HIV-1 by 12 months in the two study arms and determine the timing of HIV-1 infection. In addition, we will monitor maternal and infant renal function in preparation for a larger randomized clinical trial in Africa. The results of this study will help guide the design of a multi-site clinical trial with adequate power to determine the effect of HSV-2 suppression on vertical (MTCT) transmission of HIV-1 infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 seropositive

• HSV-2 seropositive

• Plans to deliver in Nairobi

• Resides and plans to remain in Nairobi for 12 months postpartum

• 18 years of age or older

• CD4 count>250 cells/µl

Exclusion Criteria:

• indication for highly active antiretroviral therapy (e.g., WHO stage III or IV)

• hypersensitivity to valacyclovir or acyclovir

Related Conditions & MeSH terms

• Herpes Simplex
• HIV Infections

Intervention

Drug:
• valacyclovir
500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum
• placebo
oral placebo twice daily from 34 weeks gestation to 1 year postpartum

Locations

Country	Name	City	State
Kenya	Mathare North City Clinic	Nairobi

Sponsors (4)

Lead Sponsor	Collaborator
University of Washington	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Puget Sound Partners for Global Health, Royalty Research Fund - University of Washington

Country where clinical trial is conducted

Kenya, 

References & Publications (21)

Andrews WW, Kimberlin DF, Whitley R, Cliver S, Ramsey PS, Deeter R. Valacyclovir therapy to reduce recurrent genital herpes in pregnant women. Am J Obstet Gynecol. 2006 Mar;194(3):774-81. — View Citation

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Chen KT, Segú M, Lumey LH, Kuhn L, Carter RJ, Bulterys M, Abrams EJ; New York City Perinatal AIDS Collaborative Transmission Study (PACTS) Group. Genital herpes simplex virus infection and perinatal transmission of human immunodeficiency virus. Obstet Gynecol. 2005 Dec;106(6):1341-8. — View Citation

Chuachoowong R, Shaffer N, Siriwasin W, Chaisilwattana P, Young NL, Mock PA, Chearskul S, Waranawat N, Chaowanachan T, Karon J, Simonds RJ, Mastro TD. Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. Bangkok Collaborative Perinatal HIV Transmission Study Group. J Infect Dis. 2000 Jan;181(1):99-106. — View Citation

Conant MA, Schacker TW, Murphy RL, Gold J, Crutchfield LT, Crooks RJ; International Valaciclovir HSV Study Group. Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials. Int J STD AIDS. 2002 Jan;13(1):12-21. — View Citation

Dabis F, Msellati P, Meda N, Welffens-Ekra C, You B, Manigart O, Leroy V, Simonon A, Cartoux M, Combe P, Ouangré A, Ramon R, Ky-Zerbo O, Montcho C, Salamon R, Rouzioux C, Van de Perre P, Mandelbrot L. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mère-Enfant. Lancet. 1999 Mar 6;353(9155):786-92. — View Citation

Drake AL, John-Stewart GC, Wald A, Mbori-Ngacha DA, Bosire R, Wamalwa DC, Lohman-Payne BL, Ashley-Morrow R, Corey L, Farquhar C. Herpes simplex virus type 2 and risk of intrapartum human immunodeficiency virus transmission. Obstet Gynecol. 2007 Feb;109(2 Pt 1):403-9. Erratum in: Obstet Gynecol. 2007 Apr;109(4):1002-3. — View Citation

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Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J, Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. 1999 Aug 5;341(6):394-402. — View Citation

Iliff PJ, Piwoz EG, Tavengwa NV, Zunguza CD, Marinda ET, Nathoo KJ, Moulton LH, Ward BJ, Humphrey JH; ZVITAMBO study group. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS. 2005 Apr 29;19(7):699-708. — View Citation

Kimberlin DF, Weller S, Whitley RJ, Andrews WW, Hauth JC, Lakeman F, Miller G. Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Am J Obstet Gynecol. 1998 Oct;179(4):846-51. — View Citation

Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA 3rd, Whitehouse J, Moye J Jr, Reichelderfer P, Harris DR, Fowler MG, Mathieson BJ, Nemo GJ. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. 1999 Aug 5;341(6):385-93. — View Citation

Mole L, Ripich S, Margolis D, Holodniy M. The impact of active herpes simplex virus infection on human immunodeficiency virus load. J Infect Dis. 1997 Sep;176(3):766-70. — View Citation

Nagot N, Ouédraogo A, Foulongne V, Konaté I, Weiss HA, Vergne L, Defer MC, Djagbaré D, Sanon A, Andonaba JB, Becquart P, Segondy M, Vallo R, Sawadogo A, Van de Perre P, Mayaud P; ANRS 1285 Study Group. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(8):790-9. — View Citation

Newell ML. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS. 1998 May 28;12(8):831-7. Review. — View Citation

Ozouaki F, Ndjoyi-Mbiguino A, Legoff J, Onas IN, Kendjo E, Si-Mohamed A, Mbopi-Kéou FX, Malkin JE, Bélec L. Genital shedding of herpes simplex virus type 2 in childbearing-aged and pregnant women living in Gabon. Int J STD AIDS. 2006 Feb;17(2):124-7. — View Citation

Panteleeff DD, John G, Nduati R, Mbori-Ngacha D, Richardson B, Kreiss J, Overbaugh J. Rapid method for screening dried blood samples on filter paper for human immunodeficiency virus type 1 DNA. J Clin Microbiol. 1999 Feb;37(2):350-3. — View Citation

Shaffer N, Roongpisuthipong A, Siriwasin W, Chotpitayasunondh T, Chearskul S, Young NL, Parekh B, Mock PA, Bhadrakom C, Chinayon P, Kalish ML, Phillips SK, Granade TC, Subbarao S, Weniger BG, Mastro TD. Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group. J Infect Dis. 1999 Mar;179(3):590-9. — View Citation

Sheffield JS, Hill JB, Hollier LM, Laibl VR, Roberts SW, Sanchez PJ, Wendel GD Jr. Valacyclovir prophylaxis to prevent recurrent herpes at delivery: a randomized clinical trial. Obstet Gynecol. 2006 Jul;108(1):141-7. Erratum in: Obstet Gynecol. 2006 Sep;108(3 Pt 1):695. — View Citation

Whitehead S, Bollen L, Leelawiwat W, et al. Maternal HSV-2 Cervicovaginal Shedding Increases the Risk of Intra-partum HIV-1 Transmission. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles, 2007.

Workowski KA, Berman SM. Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis. 2007 Apr 1;44 Suppl 3:S73-6. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in HIV-1 Levels in Plasma Between 34 and 38 Weeks Gestation	Calculated as log10 plasma viral load at 34 weeks gestation - log10 plasma viral load at 38 weeks gestation	4 weeks
Secondary	Vertical HIV-1 Transmission	Mother-to-child HIV transmission	1 year postpartum