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4 results on '"Watera, C"'

1. Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis.

Author

Jordan MR, Penazzato M, Cournil A, Vubil A, Jani I, Hunt G, Carmona S, Maphalala G, Mthethwa N, Watera C, Kaleebu P, Musanhu CC, Mtapuri-Zinyowera S, Dzangare J, Peeters M, Yang C, Parkin N, and Bertagnolio S

Subjects
Africa South of the Sahara epidemiology, Anti-HIV Agents therapeutic use, Female, Genotype, HIV Infections drug therapy, HIV Infections virology, HIV-1 genetics, Humans, Infant, Infant, Newborn, Male, Mozambique epidemiology, Reverse Transcriptase Inhibitors therapeutic use, Risk Factors, Surveys and Questionnaires, Uganda epidemiology, Viral Load, Drug Resistance, Viral, HIV Infections diagnosis, HIV Infections epidemiology, HIV-1 drug effects, Infectious Disease Transmission, Vertical prevention & control
Abstract

Background: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited., Methods: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance., Results: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only., Conclusions: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Published
2017
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2. Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda.

Author

Kaleebu P, Kirungi W, Watera C, Asio J, Lyagoba F, Lutalo T, Kapaata AA, Nanyonga F, Parry CM, Magambo B, Nazziwa J, Nannyonjo M, Hughes P, Hladik W, Ruberantwari A, Namuwenge N, Musinguzi J, Downing R, and Katongole-Mbidde E

Subjects
Adult, Female, HIV Infections drug therapy, HIV Infections epidemiology, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Uganda epidemiology, Viral Load, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, HIV Infections virology, HIV-1 drug effects
Abstract

Background: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR)., Methods: We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points., Results: Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥ 70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count < 250 cells/μl (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥ 100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14)., Conclusion: Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.

Published
2015
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3. Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala.

Author

Ndembi N, Hamers RL, Sigaloff KC, Lyagoba F, Magambo B, Nanteza B, Watera C, Kaleebu P, and Rinke de Wit TF

Subjects
Cross-Sectional Studies, Female, Genes, pol drug effects, Genotype, HIV Infections genetics, HIV Infections transmission, HIV-1 drug effects, Humans, Male, Pregnancy, Prevalence, Uganda, Young Adult, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV-1 genetics
Abstract

Objective: To assess the emergence of transmitted HIV-1 drug resistance (TDR) in Kampala, Uganda, 10 years after the scale-up of antiretroviral treatment (ART) and to compare with a previous survey among antenatal clinic attendees in 2007 (reporting 0% TDR)., Design: A cross-sectional survey was conducted among newly HIV-1 diagnosed, antiretroviral-naive young adults attending two large voluntary counseling and testing centers within the geographic area of Kampala., Methods: Proxy criteria for recent HIV-1 infection were used as defined by the WHO. Population sequencing of the pol gene was performed on plasma samples with HIV-1 RNA at least 1000 copies/ml. Surveillance drug resistance mutations (SDRMs) were identified according to the 2009 WHO list for surveillance of TDR. HIV-1 subtypes were designated using maximum likelihood phylogenetic reconstruction., Results: : Genotypic test results were obtained for 70 of 77 (90.9%) participants. SDRMs were identified in six samples yielding a prevalence of TDR of 8.6% (95% confidence interval 3.2-17.7%). Two had SDRMs to nucleoside reverse-transcriptase inhibitors (D67G and L210W), three had SDRMs to nonnucleoside reverse transcriptase inhibitors (G190A, G190S, and K101E), and one had SDRMs to protease inhibitors (N88D). Frequencies of HIV-1 subtypes were A (36/70, 51.4%), C ( two of 70; 2.9%), D (23/70, 32.9%), and unique recombinant forms (nine of 70, 12.9%)., Conclusion: This repeated survey suggests an increase in TDR in Kampala, compared with a previous survey. This finding justifies increased vigilance with respect to surveillance of TDR in areas in Africa where ART programs are rolled-out.

Published
2011
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4. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

Author

Gregson, J, Tang, M, Ndembi, N, Hamers, Rl, Marconi, Vc, Brooks, K, Theys, K, Arruda, M, Garcia, F, Monge, S, Kanki, Pj, Kumarasamy, N, Kerschberger, B, Mor, O, Charpentier, C, Todesco, E, Rokx, C, Gras, L, Halvas, Ek, Sunpath, H, Carlo, Dd, Antinori, A, Andreoni, M, Latini, A, Mussini, C, Aghokeng, A, Sonnerborg, A, Neogi, U, Fessel, Wj, Agolory, S, Yang, C, Blanco, Jl, Juma, Jm, Smit, E, Schmidt, D, Watera, C, Asio, J, Kirungi, W, Tostevin, A, Clumeck, N, Goedhals, D, Bester, Pa, Sabin, C, Mukui, I, Santoro, M, Perno, Cf, Hunt, G, Morris, L, Pillay, D, Schulter, E, Reyes-Teran, G, Romero, K, Avila-Rios, S, Sirivichayakul, S, Ruxrungtham, K, Mekprasan, S, Dunn, D, Kaleebu, P, Raizes, E, Kantor, R, Gupta, Rk, Rhee, S, Shafer, Rw, de Wit, Tfr, Diero, L, Camacho, R, Gunthard, Hf, Hoffmann, Cj, Di Carlo, D, El-Hay, T, van Vuuren, C, de Oliveira, T, Murakami-Ogasawara, A, [Pillay, Deenan] UCL, Dept Infect, London WC1E 6BT, England, [Gupta, Ravindra K.] UCL, Dept Infect, London WC1E 6BT, England, [Tang, Michele] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Rhee, Soo-Yon] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Gregson, John] London Sch Hyg & Trop Med, Dept Stat, London, England, [Ndembi, Nicaise] Inst Human Virol Nigeria, Abuja, Federal Capital, Nigeria, [Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands, [de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands, [Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands, [de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands, [Marconi, Vincent C.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA, [Marconi, Vincent C.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA, [Diero, Lameck] Moi Univ, Eldoret, Kenya, [Diero, Lameck] Acad Model Providing Access Healthcare, Eldoret, Kenya, [Brooks, Katherine] Brown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA, [Theys, Kristof] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Camacho, Ricardo] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Kantor, Rami] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Arruda, Monica] Univ Fed Rio de Janeiro, Inst Biol, LVM, BR-21941 Rio De Janeiro, Brazil, [Garcia, Frederico] Complejo Hosp Univ Granada, Granada, Spain, Univ Alcala de Henares, E-28871 Alcala De Henares, Spain, [Monge, Susana] CIBERESP, Madrid, Spain, [Gunthard, Huldrych F.] Univ Zurich, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland, [Gunthard, Huldrych F.] Univ Zurich, Inst Med Virol, Zurich, Switzerland, [Hoffmann, Christopher J.] Johns Hopkins Univ, Baltimore, MD USA, [Hoffmann, Christopher J.] Aurum Inst, Johannesburg, South Africa, [Kanki, Phyllis J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA, [Kumarasamy, Nagalingeshwaran] VHS, YRGCARE Med Ctr, Chennai, Tamil Nadu, India, [Kerschberger, Bernard] Med Sans Frontieres Operat Ctr Geneva, Mbabane, Eswatini, [Mor, Orna] Israel Minist Hlth, Publ Hlth Serv, Cent Virol Lab, Jerusalem, Israel, [Charpentier, Charlotte] Univ Paris Diderot, Sorbonne Paris Cite, IAME, UMR 1137, Paris, France, [Charpentier, Charlotte] INSERM, IAME, UMR 1137, Paris, France, [Charpentier, Charlotte] Hop Bichat Claude Bernard, AP HP, Virol Lab, F-75018 Paris, France, [Todesco, Eva] Hop La Pitie Salpetriere, Lab Virol, Paris, France, [Rokx, Casper] Erasmus Univ, Med Ctr, Dept Internal Med Infect Dis, Rotterdam, Netherlands, [Gras, Luuk] Stichting HIV Monitoring, Amsterdam, Netherlands, [Halvas, Elias K.] Univ Pittsburgh, Pittsburgh, PA USA, [Sunpath, Henry] Ethekwini Dist Hlth Off, Kwa Zulu, South Africa, [Di Carlo, Domenico] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy, [Santoro, Maria M.] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy, [Antinori, Antonio] INMI L Spallanzani, Infect Dis Unit, Rome, Italy, [Andreoni, Massimo] Univ Hosp Tor Vergata, Clin Infect Dis, Rome, Italy, [Latini, Alessandra] San Gallicano Dermatol Inst, HIV AIDS Unit, Rome, Italy, [Mussini, Cristina] Azienda Osped Univ Policlin, Clin Infect Dis, Modena, Italy, [Aghokeng, Avelin] Virol Lab CREMER IMPM, Yaounde, Cameroon, [Sonnerborg, Anders] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden, [Sonnerborg, Anders] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden, [Sonnerborg, Anders] Karolinska Univ Hosp, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Univ Hosp, Stockholm, Sweden, [Fessel, William J.] Kaiser Permanente Med Care Program Northern Calif, San Francisco, CA USA, [Agolory, Simon] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Raizes, Elliot] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Yang, Chunfu] Ctr Dis Control & Prevent, Int Lab Branch, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Blanco, Jose L.] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer, Clin Univ, Barcelona, Spain, [Juma, James M.] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania, [Smit, Erasmus] Publ Hlth England, Publ Hlth Lab, Birmingham, W Midlands, England, [Schmidt, Daniel] Robert Koch Inst, Dept Infect Dis Epidemiol HIV AIDS STI & Blood Bo, Berlin, Germany, [Watera, Christine] Uganda Res Unit AIDS, Entebbe, Uganda, [Asio, Juliet] Uganda Res Unit AIDS, Entebbe, Uganda, [Kaleebu, Pontiano] Uganda Res Unit AIDS, Entebbe, Uganda, [Tostevin, Anna] Minist Hlth, Kampala, Uganda, [Tostevin, Anna] UCL, MRC Clin Trials Unit, London, England, [Dunn, David] UCL, MRC Clin Trials Unit, London, England, [El-Hay, Tal] IBM Haifa Res Lab, Haifa, Israel, [Clumeck, Nathan] Univ Libre Bruxelles, St Pierre Univ Hosp, Brussels, Belgium, [Goedhals, Dominique] Univ Orange Free State, Dept Med Microbiol & Virol, Natl Hlth Lab Serv, Bloemfontein, South Africa, [van Vuuren, Cloete] Univ Orange Free State, Dept Med Microbiol & Virol, Natl Hlth Lab Serv, Bloemfontein, South Africa, [Sabin, Caroline] UCL, Infect & Populat Hlth, London, England, [Mukui, Irene] Minist Hlth, Natl AIDS & STI Control Programme, Nairobi, Kenya, [Perno, Carlo F.] INMI L Spallanzani, Antiretroviral Drugs Monitoring Unit, Rome, Italy, [Hunt, Gillian] Natl Inst Communicable Dis, Johannesburg, South Africa, [Morris, Lynn] Natl Inst Communicable Dis, Johannesburg, South Africa, [de Oliveira, Tulio] Wellcome Trust Africa Ctr Hlth & Populat Studies, Durban, South Africa, [Pillay, Deenan] Wellcome Trust Africa Ctr Hlth & Populat Studies, Durban, South Africa, [de Oliveira, Tulio] Univ KwaZulu Natal, Coll Hlth Sci, Durban, South Africa, [Schulter, Eugene] Univ Cologne, Inst Virol, D-50931 Cologne, Germany, [Murakami-Ogasawara, Akio] Natl Inst Resp Dis, Ctr Res Infect Dis, Mexico City, DF, Mexico, [Sirivichayakul, Sunee] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Ruxrungtham, Kiat] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Mekprasan, Suwanna] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Kaleebu, Pontiano] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda, Wellcome Trust, MRC, NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, and Medical Research Council

Subjects
Cyclopropanes, Anti-HIV Agents, K65r, Drug Resistance, Antiretroviral Therapy, HIV Infections, Global Health, Settore MED/07, Virological failure, Tenofovir disoproxil fumarate, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Humans, Emtricitabine, Transmission, Highly Active, Viral, Tenofovir, Africa South of the Sahara, Benzoxazines, HIV-1, Lamivudine, Pre-Exposure Prophylaxis, Retrospective Studies, Reverse Transcriptase Inhibitors, Viral Load, Hiv-1-infected patients, virus diseases, Articles, Antiretroviral therapy, Naive patients, Alkynes, Efavirenz
Abstract

Summary Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count

Published
2016

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