Browsing by Author "Newell, Kevin"

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    Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda
    (AIDS, 2009) Reynolds, Steven J.; Nakigozi, Gertrude; Newell, Kevin; Ndyanabo, Anthony; Galiwongo, Ronald; Iga, Boaz; Quinn, Thomas C.; Gray, Ron; Wawer, Maria; Serwadda, David
    Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring. Design—Observation cohort Methods—Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months. Results—1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4–29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load (VL) >400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced
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    Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda
    (AIDS (London, England), 2009-03) Reynolds, Steven J.; Nakigozi, Gertrude; Newell, Kevin; Ndyanabo, Anthony; Ronald, Galiwongo; Iga, Boaz; . Quinn, Thomas C; Gray, Ron; Wawer, Maria; Serwadda, David
    Objective—Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring. Design—Observation cohort Methods—Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months. Results—1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4–29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load (VL) >400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced both an immunologic and virologic failure endpoint (2 VL>400 copies/ml) during follow-up. Conclusions—Immunologic failure criteria performed poorly in our setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 VL being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in our setting
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    Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda
    (The Journal of infectious diseases, 2015) Gianella, Sara; Redd, Andrew D.; Grabowski, Mary K.; Tobian, Aaron A. R.; Serwadda, David; Newell, Kevin; Patel, Eshan U.; Kalibbala, Sarah; Ssebbowa, Paschal; Gray, Ronald H.; Quinn, Thomas C.; Reynolds, Steven J.
    Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNAviral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre- ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.
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    Virologic versus immunologic monitoring and the rate of accumulated genotypic resistance to first-line antiretroviral drugs in Uganda
    (BMC infectious diseases, 2012) Reynolds, Steven J; Sendagire, Hakim; Newell, Kevin; Castelnuovo, Barbara; Nankya, Immaculate; Kamya, Moses; Quinn, Thomas C.; Manabe, Yukari C.; Kambugu, Andrew
    Viral load monitoring (VLM) to identify individuals failing antiretroviral therapy (ART) is not widely available in resource-limited settings. We compared the genotypic resistance patterns between clients with VLM versus immunological monitoring (IM).Between 2004–2008, 559 ART naïve clients were enrolled in a prospective cohort, initiated on ART, and monitored with viral load (VL) and CD4+ cell counts every 6 months (VLM group). From February 2008 through June 2009, 998 clients on ART for 36–40 months (corresponding to the follow-up time of the VLM group) at the same clinic and monitored with CD4+ cell counts every 6 months were recruited into a cross sectional study (IM group). Samples from VLM clients at 12, 24 and 36 months and IM clients at 36–40 months with VL > 2000 copies/ml underwent genotypic drug resistance testing.Baseline characteristics were similar. Virologic failure (VL > 400 copies/ml) at 12, 24 and 36 months in the VLM group were 12%, 6% and 8% respectively, and in the IM group 10% at 36–40 months. Samples from 39 VLM and 70 IM clients were genotyped. 23/39 (59%) clients in the VLM group (at 12, 24 or 36 months) compared to 63/70 (90%) in the IM group, (P < 0.0001) had at least 1 non-nucleoside reverse transcriptase mutation. 19/39 (49%) of VLM clients had an M184V mutation compared to 61/70 (87%) in the IM group (P < 0.0001). Only 2/39 (5%) of VLM clients developed thymidine analogue mutations compared to 34/70 (49%) of IM clients (P < 0.0001).Routine VL monitoring reduced the rate of accumulated genotypic resistance to commonly used ART in Uganda.