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Wester, C

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Wester

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Wester, C
Author's Publications: search.filters.isAuthorOfPublication.f6aaed55-12cf-4ef3-8fc3-ad2a8df7afb1

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    Risk Factors for Symptomatic Hyperlactatemia and Lactic Acidosis Among Combination Antiretroviral Therapy-Treated Adults in Botswana: Results from a Clinical Trial
    (Mary Ann Liebert Inc., 2012) Wester, C; Eden, Svetlana K.; Shepherd, Bryan E.; Bussmann, Hermann; Novitsky, Vladimir; Samuels, David C.; Hendrickson, Sher L.; Winkler, Cheryl A.; O, Stephen J.; Essex, Myron; D, Richard T.; DeGruttola, Victor; Marlink, Richard
    Nucleoside analogue reverse transcriptase inhibitors are an integral component of combination antiretroviral treatment regimens. However, their ability to inhibit polymerase-γ has been associated with several mitochondrial toxicities, including potentially life-threatening lactic acidosis. A total of 650 antiretroviral-naive adults (69% female) initiated combination antiretroviral therapy (cART) and were intensively screened for toxicities including lactic acidosis as part of a 3-year clinical trial in Botswana. Patients were categorized as no lactic acidosis symptoms, minor symptoms but lactate <4.4 mmol/liter, and symptoms with lactate ≥ 4.4 mmol/liter [moderate to severe symptomatic hyperlactatemia (SH) or lactic acidosis (LA)]. Of 650 participants 111 (17.1%) developed symptoms and/or laboratory results suggestive of lactic acidosis and had a serum lactate drawn; 97 (87.4%) of these were female. There were 20 events, 13 having SH and 7 with LA; all 20 (100%) were female (p<0.001). Cox proportional hazard analysis limited to the 451 females revealed that having a higher baseline BMI was predictive for the development of SH/LA [aHR=1.17 per one-unit increase (1.08-1.25), p<0.0001]. Ordered logistic regression performed among all 650 patients revealed that having a lower baseline hemoglobin [aOR=1.28 per one-unit decrease (1.1-1.49), p=0.002] and being randomized to d4T/3TC-based cART [aOR=1.76 relative to ZDV/3TC (1.03-3.01), p=0.04] were predictive of the symptoms and/or the development of SH/LA. cART-treated women in sub-Saharan Africa, especially those having higher body mass indices, should receive additional monitoring for SH/LA. Women presently receiving d4T/3TC-based cART in such settings also warrant more intensive monitoring.
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    Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana
    (New England Journal of Medicine (NEJM/MMS), 2010) Shapiro, R.L.; Hughes, M.D.; Ogwu, Anthony; Kitch, Doug; Lockman, Shahin; Moffat, C.; Makhema, Joseph; Moyo, Sikhulile; Thior, Ibou; McIntosh, Kenneth; van Widenfelt, E.; Leidner, Jean; Powis, Kathleen; Asmelash, A.; Tumbare, E.; Zwerski, S.; Sharma, Upasna; Handelsman, E.; Mburu, K.; Jayeoba, O.; Moko, E.; Souda, Shashidhar Vaman; Lubega, E.; Akhtar, M.; Wester, C; Tuomola, R.; Snowden, W.; Martinez-Tristani, M.; Mazhani, L.; Essex, Myron
    BACKGROUND: The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS: We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS: The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS: All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%.
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    Virologic, Immunologic and Clinical Responses in Foreign-Born versus US-Born HIV-1 Infected Adults Initiating Antiretroviral Therapy: An Observational Cohort Study
    (Public Library of Science, 2012) Parrish, Deidra D.; Blevins, Meridith; Stinnette, Samuel E.; Rebeiro, Peter F.; Shepherd, Bryan E.; Sterling, Timothy R.; McGowan, Catherine C.; Wester, C
    Introduction: Mortality rates within the first year of combination antiretroviral therapy (cART) initiation are several-fold higher in resource-limited countries than in resource-replete settings. However studies in western countries examining virologic, immunologic and clinical responses after cART initiation in indigenous versus non-indigenous populations have shown mixed results. This study aimed to determine whether there is a difference in these outcomes in a United States setting between foreign-born and US-born patients. Methods: This retrospective observational cohort study of HIV-1 infected adults in one urban clinic in the United States compared virologic suppression, immune recovery and rates of AIDS defining events (ADEs) within the first year of cART using linear mixed effect models, log rank tests and Cox proportional hazard models. Data were analyzed for 94 foreign-born and 1242 US-born patients. Results: Foreign-born patients were younger (31.7 years versus 38.5 years), more often female (38.3% versus 27.1%), less often injection drug users (3.2% versus 9.5%) or men who have sex with men (19.0% versus 54.5%), and had higher loss to follow-up rates (14.9% versus 6.2%). No significant differences were detected between the groups in suppression of plasma HIV-1 RNA, CD4+ cell recovery or development of ADEs. Conclusions: During the first year on cART, virologic suppression, immune recovery and development of ADEs were comparable between foreign-born and US-born patients in care in a US clinic. Differential rates of loss to follow-up warrant further investigation in the foreign-born population.
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    HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission
    (Public Library of Science, 2010) Baum, Marianna; Thior, Ibou; Asmelash, Aida; Campa, Adriana; van Widenfelt, Erik; Mine, Madisa; Moffat, Claire; Mmalane, Mompati; Gilbert, Peter; Novitsky, Vladimir; Wang, Rui; Bussmann, Hermann; Lockman, Shahin; Shapiro, Roger; Wester, Carolyn; Wester, C; Ogwu, Anthony; Musonda, Rosemary; Moyo, Sikhulile; Makhema, Joseph; Marlink, Richard; Seage, George; DeGruttola, Victor; Essex, Myron
    The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities.
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    Nutrition and Inflammation Serum Biomarkers Are Associated with 12-Week Mortality among Malnourished Adults Initiating Antiretroviral Therapy in Zambia
    (BioMed Central, 2011) Blevins, Meridith; Nyirenda, Christopher; Zulu, Isaac; Mwango, Albert; Koethe, John R.; Kabagambe, Edmond K.; Shepherd, Bryan E.; Wester, C; Chiasera, Janelle M.; Mulenga, Lloyd B.; Heimburger, Douglas C.
    Background: A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described. Methods: An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under \(16 kg/m^2\) or \(CD4^+\) lymphocyte counts of less than \(50 cells/mm^3\), or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality. Results: Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not. Conclusions: The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.