Browsing by Author "Godfrey, Catherine"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Barriers to HIV remission research in low- and middle-income countries
    (Wiley Open Access, 2017) Rossouw, Theresa; Tucker, Joseph D.; Van Zyl, Gert U.; Sikwesi, Kenly; Godfrey, Catherine
    Introduction: HIV eradication and remission research has largely taken place in high-income countries. In low- and middleincome countries (LMIC), there may be factors that have a substantial impact on the size of the latent HIV reservoir and the immunological response to infection. If a curative strategy is to be available to all HIV-infected individuals, these factors must be understood. Methods: We use a scoping review to examine the literature on biological factors that may have an impact on HIV persistence in LMIC. Three databases were searched without date restrictions. Results: Uncontrolled viral replication and higher coinfection prevalence may alter the immunological milieu of individuals in LMIC and increase the size of the HIV reservoir. Differences in HIV subtype could also influence the measurement and size of the HIV reservoir. Immune activation may differ due to late presentation to care, presence of chronic infections, increased gut translocation of bacterial products and poor nutrition. Conclusions: Research on HIV remission is urgently needed in LMIC. Research into chronic immune activation in resource poor environments, the immune response to infection, the mechanisms of HIV persistence and latency in different viral clades and the effect of the microbiological milieu must be performed. Geographic differences, which may be substantial and may delay access to curative strategies, should be identified.
  • Thumbnail Image
    Item
    Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings
    (Oxford University Press, 2020-10) Wallis, Carole L.; Hughes, Michael D.; Ritz, Justin; Viana, Raquel; de Jesus, Carlos Silva; Saravanan, Shanmugam; van Schalkwyk, Marije; Mngqibisa, Rosie; Salata, Robert; Mugyenyi, Peter; Hogg, Evelyn; Hovind, Laura; Wieclaw, Linda; Gross, Robert; Godfrey, Catherine; Collier, Ann C.; Grinsztejn, Beatriz; Mellors, John W.
    Background: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Methods: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. Results: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. Conclusions: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.