Publications (10)53.04 Total impact
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Article: An Evaluation of HIV-1 RNA Viral Load Quantification in Plasma and Dried Blood Spots Using the Semi-automated COBAS Amplicor and Fully Automated COBAS Ampliprep/Taqman version 2.0 in Kisumu, Kenya.
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ABSTRACT: In Kenya, HIV-1 viral load monitoring is commonly performed with the COBAS Amplicor using plasma specimens. Interest is growing in transitioning to real-time PCR (RT-PCR), such as the COBAS Ampliprep/COBAS Taqman (CAP/CTM), using dried blood spots (DBS). Before implementation, direct evaluation of the two assays using DBS field specimens is required. This study compares sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, concordance, and agreement between HIV-1 viral load measurements using plasma and DBS specimens obtained from 512 HIV-1 infected pregnant females enrolled in the Kisumu Breastfeeding Study, and tested with the COBAS Amplicor and CAP/CTM assays. The sensitivity and NPV of viral load detection in DBS specimens were higher with CAP/CTM (sensitivity: 100%, 95% CI: 99.1-100.0; NPV: 100%, 95% CI: 59.0-100.0%) than the COBAS Amplicor (sensitivity: 96.6%, 95% CI: 94.3-98.1; NPV: 58.8%, 95% CI: 40.7-75.4). PPV was comparable between both assays when using DBS. The specificity of viral load detection in DBS specimens was lower with CAP/CTM (77.8%, 95% CI: 40.0-97.2) than the COBAS Amplicor (95.2%, 95% CI: 76.2-99.9). Good concordance and agreement were observed when testing paired plasma and DBS specimens with both assays. Lower specificity with the CAP/CTM is likely due to pro-viral HIV-1 DNA amplification and lower detection limits with RT-PCR. However, the CAP/CTM has better sensitivity and higher throughput when compared with the COBAS Amplicor. These findings suggest that DBS may be a suitable alternative to plasma when using RT-PCR, which could increase access to viral load monitoring in resource limited settings.Journal of clinical microbiology 02/2013; · 4.16 Impact Factor -
Article: Rash, Hepatotoxicity and Hyperbilirubinemia Among Kenyan Infants Born to HIV-infected Women Receiving Triple-antiretroviral Drugs for the Prevention of Mother-to-child HIV Transmission.
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ABSTRACT: We compared adverse events among breast-feeding neonates born to Kenyan mothers receiving triple-antiretroviral therapy, including either nevirapine or nelfinavir. Nevirapine-exposed infants had an absolute increase in the risk of rash but no significant risk differences for hepatotoxicity or high-risk hyperbilirubinemia compared with nelfinavir-exposed infants. From an infant-safety perspective, nevirapine-based regimens given during pregnancy and breast-feeding are viable options where alternatives to breast milk are not safe, affordable or feasible.The Pediatric Infectious Disease Journal 07/2012; 31(11):1155-7. · 3.58 Impact Factor -
Article: CD4, Viral Load Response, and Adherence Among Antiretroviral-Naive Breast-feeding Women Receiving Triple Antiretroviral Prophylaxis for Prevention of Mother-to-Child Transmission of HIV in Kisumu, Kenya.
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ABSTRACT: BACKGROUND:: Health benefits and survival of an exclusively breast-fed infant is dependent on the mother's health; thus, the need for antiretroviral (ARV) intervention for prevention of mother-to-child transmission (PMTCT). Achieving maternal health benefits from these regimens requires adherence to the treatments and close monitoring. We evaluated virologic, immunologic responses, and adherence among women receiving maternal triple ARV prophylaxis consisting of lamivudine/zidovudine and nevirapine or nelfinavir in the Kisumu Breastfeeding Study. METHODS:: We analyzed baseline demographic data, trends in CD4 count, and viral load (VL) at enrollment (32-34 weeks gestation), delivery, 14 and 24 weeks postpartum among 434 women who remained in the study at 24 weeks postpartum. Adherence rates were determined using pill counts reinforced by self-report and drug calendar. We dichotomized adherence as ≥95% versus <95%. RESULTS:: Among the 434 women, 84% (n = 366) had adherence ≥95%. The proportion of women with undetectable VL (<400 copies/mL) increased from 6% at baseline to 79%, and that of those with CD4 count <250 cells per microliter decreased from 23% (100) at baseline to 5% (22) at 24 weeks postpartum. In discrete-survival model, time to achieving VL suppression was associated with baseline VL <5.0 log copies per milliliter, parity ≥2, and use of nelfinavir- versus nevirapine-based ARV. Association between undetectable VL with duration of therapy (P < 0.0001) and adherence with suppression of VL (P = 0.001) was observed. CONCLUSIONS:: High baseline VL and short exposure to ARVs for PMTCT are risk factors for failing to achieve undetectable VL. These findings support the new WHO guidelines for early initiation of ARV prophylaxis for PMTCT for maximal reduction of maternal VL.JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2012; 61(2):249-257. · 4.43 Impact Factor -
Article: Nevirapine-Associated Hepatotoxicity and Rash among HIV-Infected Pregnant Women in Kenya.
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ABSTRACT: Background: Few studies have evaluated the risk of nevirapine (NVP)-associated hepatotoxicity among HIV-infected pregnant women with a CD4 count ≥250 cells/mm(3). We enrolled HIV-infected pregnant Kenyan women who initiated triple antiretroviral therapy (ART) at 34 weeks gestation. We compared the rates of severe hepatotoxicity (grades 3-4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) with NVP and nelfinavir (NFV), respectively. We initiated triple ART in 522 pregnant women; severe hepatotoxicity and rash-associated hepatotoxicity occurred in 14 (3%) and 9 (2%) women, respectively. Women who initiated NVP had higher rates of severe hepatotoxicity (5% vs 1%; P = .03) and rash-associated hepatotoxicity (4% vs 0%; P = .003) when compared with NFV. Among women who initiated NVP (n = 254), a baseline CD4 count ≥250 cells/mm(3) was not associated with severe hepatotoxicity (5% vs 3%; P = .52) or rash-associated hepatotoxicity (4% vs 3%; P = .69). Nevirapine use but not CD4 count ≥250 cells/mm(3) was associated with hepatotoxicity.Journal of the International Association of Physicians in AIDS Care (JIAPAC) 10/2011; 11(2):142-9. -
Article: Nelfinavir and its active metabolite, hydroxy-t-butylamidenelfinavir (M8), are transferred in small quantities to breast milk and do not reach biologically significant concentrations in breast-feeding infants whose mothers are taking nelfinavir.
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ABSTRACT: Antiretroviral drugs cross from maternal plasma to breast milk and from breast milk to the infant in different concentrations. We measured concentrations of nelfinavir and its active metabolite (M8) in maternal plasma and breast milk from women and in dried blood spots collected from their infants at delivery and postnatal weeks 2, 6, 14, and 24 in the Kisumu Breastfeeding Study, Kisumu, Kenya. Nelfinavir-based antiretroviral regimens given to mothers as prevention of mother-to-child HIV transmission (PMTCT) do not expose the breast-feeding infant to biologically significant concentrations of nelfinavir or M8.Antimicrobial Agents and Chemotherapy 08/2011; 55(11):5168-71. · 4.84 Impact Factor -
Article: Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial.
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ABSTRACT: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.PLoS Medicine 03/2011; 8(3):e1001015. · 16.27 Impact Factor -
Article: 2009 Pandemic influenza A H1N1 in Alaska: temporal and geographic characteristics of spread and increased risk of hospitalization among Alaska Native and Asian/Pacific Islander people.
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ABSTRACT: Alaska Native people have suffered disproportionately from previous influenza pandemics. We evaluated 3 separate syndromic data sources to determine temporal and geographic patterns of spread of 2009 pandemic influenza A H1N1 (pH1N1) in Alaska, and reviewed records from persons hospitalized with pH1N1 disease in 3 areas in Alaska to characterize clinical and epidemiologic features of disease in Alaskans. A wave of pH1N1 disease swept through Alaska beginning in most areas in August or early September. In rural regions, where Alaska Native people comprise a substantial proportion of the population, disease occurred earlier than in other regions. Alaska Native people and Asian/Pacific Islanders (A/PI) were 2-4 times more likely to be hospitalized than whites. Alaska Native people and other minorities remain at high risk for early and substantial morbidity from pandemic influenza episodes. These findings should be integrated into plans for distribution and use of vaccine and antiviral agents.Clinical Infectious Diseases 01/2011; 52 Suppl 1:S189-97. · 9.15 Impact Factor -
Article: Field experience in implementing ISO 15189 in Kisumu, Kenya.
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ABSTRACT: Quality medical laboratory services are an integral part of routine health care, medical research, and public health systems. Despite this vital role, quality laboratory services in Africa are scarce. The crucial need for expanding quality laboratory services throughout sub-Saharan Africa is especially critical because of the region's burden of disease. Fortunately, several plans from supporting international partners are underway to help strengthen laboratory infrastructure in this region. A key component of these initiatives is the enforcement of quality assurance services through accreditation by international standards such as the International Organization for Standardization (ISO) 15189. However, acquisition and maintenance of these standards are a significant challenge, especially in resource-limited settings. The most common limiting factors can include funding, government support, equipment, training opportunities, and poor procurement infrastructure. In this article, we discuss the challenges and benefits accrued in pursuing and sustaining ISO 15189 accreditation for the Kenya Medical Research Institute/Centre for Disease Control HIV-Research Laboratory in Kisumu, Kenya.American Journal of Clinical Pathology 09/2010; 134(3):410-8. · 2.60 Impact Factor -
Article: Factors affecting breastfeeding cessation after discontinuation of antiretroviral therapy to prevent mother-to-child transmission of HIV.
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ABSTRACT: In the Kisumu Breastfeeding Study (KiBS), prevention of mother-to-child HIV transmission study, highly active antiretroviral therapy (HAART) is provided from 34 weeks gestation, through delivery to six months postpartum. The study recommends that women practice exclusive breastfeeding for six months, then wean abruptly. We sought to explore factors such as, education, family support, cultural norms, and sources of information about perinatal HIV transmission, which may influence a mother's decision to comply or not comply with the study's recommendation to stop breastfeeding when HAART is discontinued. We used semi-structured interviews of a purposive sample of 18 mothers participating in the KiBS. By interviewing 10 mothers who stopped breastfeeding and eight mothers who continued, it was possible to examine how different factors may have affected the groups of participants. All participants stated that it was not traditional to stop breastfeeding at six months. Participants who stopped breastfeeding reported more family support, were more educated, and were more likely to disclose their HIV status. Participants who continued breastfeeding more often expressed concern about stigma. Participants learned about mother-to-child transmission from clinics, churches, community groups, and other HIV-positive mothers. This substudy suggests that family support, education, and cultural norms are important factors that may influence a mother's decision regarding breastfeeding cessation. Thus, counseling and family support may play integral roles in the promotion of early breastfeeding cessation.AIDS Care 07/2010; 22(7):866-73. · 1.60 Impact Factor -
Article: Effect of a point-of-use water treatment and safe water storage intervention on diarrhea in infants of HIV-infected mothers.
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ABSTRACT: To reduce mother-to-child transmission of human immunodeficiency virus (HIV) in resource-poor settings, the World Health Organization recommends exclusive breast-feeding for 6 months, followed by rapid weaning if replacement feeding is affordable, feasible, available, safe, and sustainable. In the Kisumu Breastfeeding Study (trial registration: Clinicaltrials.gov identifier NCT00146380), infants of HIV-infected mothers who received antiretroviral therapy experienced high rates of diarrhea at weaning. To address this problem, mothers in the Kisumu Breastfeeding Study were given safe water storage vessels, hygiene education, and bleach for household water treatment. We compared the incidence of diarrhea in infants enrolled before (cohort A) and after (cohort B) implementation of the intervention. Cohort B infants experienced less diarrhea than cohort A infants, before and after weaning (P < .001 and P = .047, respectively); however, during the weaning period, there were no differences in the frequency of diarrhea between cohorts (P = 0.89). Testing of stored water in cohort B homes indicated high adherence (monthly range, 80%-95%) to recommended chlorination practices. Among infants who were weaned early, provision of safe water may be insufficient to prevent weaning-associated diarrhea.The Journal of Infectious Diseases 10/2009; 200(8):1186-93. · 6.41 Impact Factor
Top co-authors
Top Journals
Institutions
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2011–2012
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Centers for Disease Control and Prevention
- Division of HIV/AIDS Prevention, Intervention and Support
Druid Hills, GA, USA
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2010
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University of Oxford
- Department of Public Health
Oxford, ENG, United Kingdom
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