Effects of Antiretroviral Therapy on Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Transmission among HIV-Infected Zambian Children

Landon N. Olp, Veenu Minhas, Clement Gondwe, Chipepo Kankasa, Janet Wojcicki, Charles Mitchell, John T West, Charles Wood

Research output: Contribution to journalArticle

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Abstract

Background: The risk of Kaposi's sarcoma-associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown. Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection - with an emphasis on HIV, ART, and immunological measures - were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan-Meier, and multivariable Cox regression models were used to assess differences in time to event (KSHV seroconversion) between groups. All statistical tests were two-sided. Results: During follow-up, 151 (52.6%) children underwent KSHV seroconversion. Based on 3552 months of follow-up, we observed similar KSHV incidence rates between HIV-infected and uninfected children. Among HIV-infected children, ART-naïve children had statistically significantly increased risk of KSHV acquisition (adjusted hazard ratio [AHR] = 5.04, 95% confidence interval [CI] = 2.36 to 10.80, P <. 001). Time-updated CD4+ T-cell percentage was also statistically significantly associated with risk of KSHV acquisition (AHR = 0.82, 95% CI = 0.74 to 0.92, P <. 001), such that each 5% increase of CD4+ T-cells represented an 18% decrease in risk of acquiring KSHV. Conclusions: Our data suggest that early ART and prevention of immune suppression reduce the risk of KSHV acquisition among HIV-infected children in an area where both viruses are highly endemic. This study highlights the importance of programs in Africa to provide children with ART immediately after HIV infection is diagnosed.

Original languageEnglish (US)
Article numberdjv189
JournalJournal of the National Cancer Institute
Volume107
Issue number10
DOIs
StatePublished - Oct 2015

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Human Herpesvirus 8
HIV
Therapeutics
Zambia
Secondary Prevention
HIV Infections
Confidence Intervals
T-Lymphocytes
Herpesviridae Infections
Incidence
Proportional Hazards Models

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Effects of Antiretroviral Therapy on Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Transmission among HIV-Infected Zambian Children. / Olp, Landon N.; Minhas, Veenu; Gondwe, Clement; Kankasa, Chipepo; Wojcicki, Janet; Mitchell, Charles; West, John T; Wood, Charles.

In: Journal of the National Cancer Institute, Vol. 107, No. 10, djv189, 10.2015.

Research output: Contribution to journalArticle

Olp, Landon N. ; Minhas, Veenu ; Gondwe, Clement ; Kankasa, Chipepo ; Wojcicki, Janet ; Mitchell, Charles ; West, John T ; Wood, Charles. / Effects of Antiretroviral Therapy on Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Transmission among HIV-Infected Zambian Children. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 10.
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abstract = "Background: The risk of Kaposi's sarcoma-associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown. Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection - with an emphasis on HIV, ART, and immunological measures - were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan-Meier, and multivariable Cox regression models were used to assess differences in time to event (KSHV seroconversion) between groups. All statistical tests were two-sided. Results: During follow-up, 151 (52.6{\%}) children underwent KSHV seroconversion. Based on 3552 months of follow-up, we observed similar KSHV incidence rates between HIV-infected and uninfected children. Among HIV-infected children, ART-na{\"i}ve children had statistically significantly increased risk of KSHV acquisition (adjusted hazard ratio [AHR] = 5.04, 95{\%} confidence interval [CI] = 2.36 to 10.80, P <. 001). Time-updated CD4+ T-cell percentage was also statistically significantly associated with risk of KSHV acquisition (AHR = 0.82, 95{\%} CI = 0.74 to 0.92, P <. 001), such that each 5{\%} increase of CD4+ T-cells represented an 18{\%} decrease in risk of acquiring KSHV. Conclusions: Our data suggest that early ART and prevention of immune suppression reduce the risk of KSHV acquisition among HIV-infected children in an area where both viruses are highly endemic. This study highlights the importance of programs in Africa to provide children with ART immediately after HIV infection is diagnosed.",
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T1 - Effects of Antiretroviral Therapy on Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Transmission among HIV-Infected Zambian Children

AU - Olp, Landon N.

AU - Minhas, Veenu

AU - Gondwe, Clement

AU - Kankasa, Chipepo

AU - Wojcicki, Janet

AU - Mitchell, Charles

AU - West, John T

AU - Wood, Charles

PY - 2015/10

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N2 - Background: The risk of Kaposi's sarcoma-associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown. Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection - with an emphasis on HIV, ART, and immunological measures - were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan-Meier, and multivariable Cox regression models were used to assess differences in time to event (KSHV seroconversion) between groups. All statistical tests were two-sided. Results: During follow-up, 151 (52.6%) children underwent KSHV seroconversion. Based on 3552 months of follow-up, we observed similar KSHV incidence rates between HIV-infected and uninfected children. Among HIV-infected children, ART-naïve children had statistically significantly increased risk of KSHV acquisition (adjusted hazard ratio [AHR] = 5.04, 95% confidence interval [CI] = 2.36 to 10.80, P <. 001). Time-updated CD4+ T-cell percentage was also statistically significantly associated with risk of KSHV acquisition (AHR = 0.82, 95% CI = 0.74 to 0.92, P <. 001), such that each 5% increase of CD4+ T-cells represented an 18% decrease in risk of acquiring KSHV. Conclusions: Our data suggest that early ART and prevention of immune suppression reduce the risk of KSHV acquisition among HIV-infected children in an area where both viruses are highly endemic. This study highlights the importance of programs in Africa to provide children with ART immediately after HIV infection is diagnosed.

AB - Background: The risk of Kaposi's sarcoma-associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown. Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection - with an emphasis on HIV, ART, and immunological measures - were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan-Meier, and multivariable Cox regression models were used to assess differences in time to event (KSHV seroconversion) between groups. All statistical tests were two-sided. Results: During follow-up, 151 (52.6%) children underwent KSHV seroconversion. Based on 3552 months of follow-up, we observed similar KSHV incidence rates between HIV-infected and uninfected children. Among HIV-infected children, ART-naïve children had statistically significantly increased risk of KSHV acquisition (adjusted hazard ratio [AHR] = 5.04, 95% confidence interval [CI] = 2.36 to 10.80, P <. 001). Time-updated CD4+ T-cell percentage was also statistically significantly associated with risk of KSHV acquisition (AHR = 0.82, 95% CI = 0.74 to 0.92, P <. 001), such that each 5% increase of CD4+ T-cells represented an 18% decrease in risk of acquiring KSHV. Conclusions: Our data suggest that early ART and prevention of immune suppression reduce the risk of KSHV acquisition among HIV-infected children in an area where both viruses are highly endemic. This study highlights the importance of programs in Africa to provide children with ART immediately after HIV infection is diagnosed.

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