Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial

Jairam R. Lingappa, Jared M. Baeten, Anna Wald, James P. Hughes, Katherine K. Thomas, Andrew Mujugira, Nelly Mugo, Elizabeth A. Bukusi, Craig R. Cohen, Elly Katabira, Allan Ronald, James Kiarie, Carey Farquhar, Grace John Stewart, Joseph Makhema, Myron Essex, Edwin Were, Kenneth H. Fife, Guy de Bruyn, Glenda E. GrayJames A. McIntyre, Rachel Manongi, Saidi Kapiga, David Coetzee, Susan Allen, Mubiana Inambao, Kayitesi Kayitenkore, Etienne Karita, William Kanweka, Sinead Delany, Helen Rees, Bellington Vwalika, Amalia S. Magaret, Richard S. Wang, Lara Kidoguchi, Linda Barnes, Renee Ridzon, Lawrence Corey, Connie Celum

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Abstract

Background: Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. We investigated the effect of aciclovir on HIV-1 progression. Methods: In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to aciclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per μL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per μL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per μL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00194519. Findings: At enrolment, the median CD4 cell count was 462 cells per μL and median HIV-1 plasma RNA was 4·1 log10 copies per μL. Aciclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned aciclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0·84, 95% CI 0·71-0·98, p=0·03). In those with CD4 counts ≥350 cells per μL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per μL by 19% (0·81, 0·71-0·93, p=0·002). Interpretation: The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. Funding: Bill & Melinda Gates Foundation.

Original languageEnglish (US)
Pages (from-to)824-833
Number of pages10
JournalThe Lancet
Volume375
Issue number9717
DOIs
StatePublished - Mar 11 2010

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Human Herpesvirus 2
Acyclovir
Disease Progression
HIV-1
Randomized Controlled Trials
Placebos
CD4 Lymphocyte Count
Southern Africa
Eastern Africa
Intention to Treat Analysis
Heterosexuality
Therapeutics
Random Allocation
Research Personnel
RNA
Viruses

ASJC Scopus subject areas

  • Medicine(all)

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Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2 : a randomised placebo-controlled trial. / Lingappa, Jairam R.; Baeten, Jared M.; Wald, Anna; Hughes, James P.; Thomas, Katherine K.; Mujugira, Andrew; Mugo, Nelly; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Kiarie, James; Farquhar, Carey; Stewart, Grace John; Makhema, Joseph; Essex, Myron; Were, Edwin; Fife, Kenneth H.; de Bruyn, Guy; Gray, Glenda E.; McIntyre, James A.; Manongi, Rachel; Kapiga, Saidi; Coetzee, David; Allen, Susan; Inambao, Mubiana; Kayitenkore, Kayitesi; Karita, Etienne; Kanweka, William; Delany, Sinead; Rees, Helen; Vwalika, Bellington; Magaret, Amalia S.; Wang, Richard S.; Kidoguchi, Lara; Barnes, Linda; Ridzon, Renee; Corey, Lawrence; Celum, Connie.

In: The Lancet, Vol. 375, No. 9717, 11.03.2010, p. 824-833.

Research output: Contribution to journalArticle

Lingappa, JR, Baeten, JM, Wald, A, Hughes, JP, Thomas, KK, Mujugira, A, Mugo, N, Bukusi, EA, Cohen, CR, Katabira, E, Ronald, A, Kiarie, J, Farquhar, C, Stewart, GJ, Makhema, J, Essex, M, Were, E, Fife, KH, de Bruyn, G, Gray, GE, McIntyre, JA, Manongi, R, Kapiga, S, Coetzee, D, Allen, S, Inambao, M, Kayitenkore, K, Karita, E, Kanweka, W, Delany, S, Rees, H, Vwalika, B, Magaret, AS, Wang, RS, Kidoguchi, L, Barnes, L, Ridzon, R, Corey, L & Celum, C 2010, 'Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial', The Lancet, vol. 375, no. 9717, pp. 824-833. https://doi.org/10.1016/S0140-6736(09)62038-9
Lingappa, Jairam R. ; Baeten, Jared M. ; Wald, Anna ; Hughes, James P. ; Thomas, Katherine K. ; Mujugira, Andrew ; Mugo, Nelly ; Bukusi, Elizabeth A. ; Cohen, Craig R. ; Katabira, Elly ; Ronald, Allan ; Kiarie, James ; Farquhar, Carey ; Stewart, Grace John ; Makhema, Joseph ; Essex, Myron ; Were, Edwin ; Fife, Kenneth H. ; de Bruyn, Guy ; Gray, Glenda E. ; McIntyre, James A. ; Manongi, Rachel ; Kapiga, Saidi ; Coetzee, David ; Allen, Susan ; Inambao, Mubiana ; Kayitenkore, Kayitesi ; Karita, Etienne ; Kanweka, William ; Delany, Sinead ; Rees, Helen ; Vwalika, Bellington ; Magaret, Amalia S. ; Wang, Richard S. ; Kidoguchi, Lara ; Barnes, Linda ; Ridzon, Renee ; Corey, Lawrence ; Celum, Connie. / Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2 : a randomised placebo-controlled trial. In: The Lancet. 2010 ; Vol. 375, No. 9717. pp. 824-833.
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T1 - Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2

T2 - a randomised placebo-controlled trial

AU - Lingappa, Jairam R.

AU - Baeten, Jared M.

AU - Wald, Anna

AU - Hughes, James P.

AU - Thomas, Katherine K.

AU - Mujugira, Andrew

AU - Mugo, Nelly

AU - Bukusi, Elizabeth A.

AU - Cohen, Craig R.

AU - Katabira, Elly

AU - Ronald, Allan

AU - Kiarie, James

AU - Farquhar, Carey

AU - Stewart, Grace John

AU - Makhema, Joseph

AU - Essex, Myron

AU - Were, Edwin

AU - Fife, Kenneth H.

AU - de Bruyn, Guy

AU - Gray, Glenda E.

AU - McIntyre, James A.

AU - Manongi, Rachel

AU - Kapiga, Saidi

AU - Coetzee, David

AU - Allen, Susan

AU - Inambao, Mubiana

AU - Kayitenkore, Kayitesi

AU - Karita, Etienne

AU - Kanweka, William

AU - Delany, Sinead

AU - Rees, Helen

AU - Vwalika, Bellington

AU - Magaret, Amalia S.

AU - Wang, Richard S.

AU - Kidoguchi, Lara

AU - Barnes, Linda

AU - Ridzon, Renee

AU - Corey, Lawrence

AU - Celum, Connie

PY - 2010/3/11

Y1 - 2010/3/11

N2 - Background: Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. We investigated the effect of aciclovir on HIV-1 progression. Methods: In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to aciclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per μL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per μL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per μL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00194519. Findings: At enrolment, the median CD4 cell count was 462 cells per μL and median HIV-1 plasma RNA was 4·1 log10 copies per μL. Aciclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned aciclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0·84, 95% CI 0·71-0·98, p=0·03). In those with CD4 counts ≥350 cells per μL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per μL by 19% (0·81, 0·71-0·93, p=0·002). Interpretation: The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. Funding: Bill & Melinda Gates Foundation.

AB - Background: Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. We investigated the effect of aciclovir on HIV-1 progression. Methods: In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to aciclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per μL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per μL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per μL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00194519. Findings: At enrolment, the median CD4 cell count was 462 cells per μL and median HIV-1 plasma RNA was 4·1 log10 copies per μL. Aciclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned aciclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0·84, 95% CI 0·71-0·98, p=0·03). In those with CD4 counts ≥350 cells per μL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per μL by 19% (0·81, 0·71-0·93, p=0·002). Interpretation: The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. Funding: Bill & Melinda Gates Foundation.

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