• Adherence to antiretroviral therapy assessed by drug level monitoring and self-report in cameroon

      Kouanfack, Charles; Laurent, Christian; Peytavin, Gilles; Ciaffi, Laura; Ngolle, Maguy; Nkene, Yvette Mawamba; Essomba, Claudine; Calmy, Alexandra; Mpoudi-Ngolé, Eitel; Delaporte, Eric; Koulla-Shiro, Sinata; Central Hospital, Yaoundé, Cameroon; Institut de recherche pour le developpement, University of Montpellier, Montpellier, France; Laboratoire de Toxicologie et de Dosage de Medicaments, Centre Hospitalier Universitaire Bichat Claude Bernard, Paris, France; Medecins Sans Frontieres, Geneva, Switzerland; Projet PRESICA (Prevention du Sida au Cameroun), Military Hospital, Yaounde, Cameroon (2008-06-01)
      OBJECTIVES: To compare adherence to antiretroviral therapy using drug level monitoring and self-report and to explore the relation between these 2 methods and viral load measurements. METHODS: Sixty patients received a fixed-dose combination of nevirapine, stavudine, and lamivudine in a clinical study in Cameroon. Adherence was assessed every 6 months until month 36 by nevirapine minimal plasma concentration and self-report. Plasma HIV-1 viral load was determined at the same time. Analyses included 159 complete observations. RESULTS: The proportion of patients labeled as "adherent" was significantly lower using nevirapine monitoring (88.7%, 95% confidence interval [CI]: 82.7 to 93.2) than self-report (97.5%, CI: 93.7 to 99.3; P = 0.002). Virologic failure was associated with the nevirapine concentration (adjusted odds ratio [aOR] = 4.43; P = 0.018) but not with the self-reported adherence (aOR = 0.84; P = 0.9). As compared with the virologic outcome, the sensitivity of nevirapine level monitoring for predicting inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4%, and the negative predictive value was 78.0%. For self-report, the respective values were 2.6%, 97.5%, 25.0%, and 75.5%. CONCLUSIONS: Drug level monitoring provided a more reliable estimate of adherence than self-report. This method could be used in research settings. Operational research is required to define how to improve the accuracy of the self-report method because it is the most feasible method in clinical practice.
    • Adherence to antiretroviral therapy in patients enrolled in a comprehensive care program in Cambodia: a 24-month follow-up assessment

      Spire, Bruno; Carrieri, Patrizia; Sopha, Pal; Protopopescu, Camelia; Prak, Narom; Quillet, Catherine; Ngeth, Chanchhaya; Ferradini, Laurent; Delfraissy, Jean-François; Laureillard, Didier; Inserm U912, Economic and Social Sciences, Health Systems and Societies, Marseille, France; Infectious Disease Department, Khmero-Sovietic Friendship Hospital, Phnom Penh, Cambodia; Médecins Sans Frontières, Paris, France; Epicentre, Paris, France; Clinical Immunology Department, Bicêtre Hospital, Kremlin Bicêtre, France; Immunological Department, Georges Pompidou, European Hospital, Paris France (2008-05)
      BACKGROUND: The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence. METHODS: Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence. RESULTS: A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence. CONCLUSIONS: At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.
    • Adults receiving HIV care before the start of antiretroviral therapy in sub-Saharan Africa: patient outcomes and associated risk factors

      Bastard, Mathieu; Nicolay, Nathalie; Szumilin, Elisabeth; Balkan, Suna; Poulet, Elisabeth; Pujades-Rodriguez, Mar (Lippincott Williams & Wilkins, 2013-12-15)
      Gaining understanding of the period before antiretroviral therapy (ART) is needed to improve treatment outcomes and to reduce HIV transmission. This study describes the cascade of enrollment in HIV care, pre-ART follow-up, and predictors of mortality and lost to follow-up (LTFU) before ART initiation.
    • Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries.

      Greig, Jane; Casas, Esther C; O'Brien, Daniel P; Mills, Edward J; Ford, Nathan; Médecins Sans Frontières, London, UK. jane.greig@london.msf.org (2012-07-31)
      Recent studies have highlighted the increased risk of adverse outcomes among older patients on antiretroviral therapy (ART). We report on the associations between older age and adverse outcomes in HIV/AIDS antiretroviral programmes across 17 programmes in sub-Saharan Africa.
    • A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa

      Van Cutsem, G; Saphonn, V; Saramony, S; Vibol, U; Zhang, FJ; Han, N; Saghayam, S; Kurniati, N; Muktiarti, D; Fong, SM; Thien, M; Nik Yusoff, NK; Hai, LC; Razali, K; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand. annette.sohn@treatasia.org (BioMed Central, 2011-04-08)
      To better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts.
    • Cascade of HIV Care and Population Biral Suppression in a High-Burden Region of Kenya

      Maman, D; Zeh, C; Mukui, I; Kirubi, B; Masson, S; Opolo, V; Szumilin, E; Riche, B; Etard, JF (Lippincott Williams & Wilkins, 2015-07-31)
      Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation - especially HIV incidence, population viral load, and ART eligibility - is rare in sub-Saharan Africa.
    • CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multicohort analysis from South Africa

      Hoffmann, Christopher J; Schomaker, Michael; Fox, Matthew P; Mutevedzi, Portia; Giddy, Janet; Prozesky, Hans; Wood, Robin; Garone, Daniela B; Egger, Matthias; Boulle, Andrew; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. choffmann@jhmi.edu (Lippincott Williams & Wilkins, 2013-05-01)
      In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.
    • CD4 Testing at Clinics to Assess Eligibility for Antiretroviral Therapy

      Lumala, R; van den Akker, T; Metcalf, CA; Diggle, E; Zamadenga, B; Mbewa, K; Akkeson, A (College of Medicine, University of Malawi, 2012-06-01)
      In 2011, the Ministry of Health raised the CD4 threshold for antiretroviral therapy (ART) eligibility from <250 cells/µl and <350 cells/µl, but at the same time only 8.8% of facilities in Malawi with HIV services provided CD4 testing. We conducted a record review at 10 rural clinics in Thyolo District to assess the impact of introducing CD4 testing on identifying patients eligible for ART.
    • Clinical screening for HIV in a health centre setting in urban Kenya: an entry point for voluntary counselling, HIV testing and early diagnosis of HIV infection?

      Arendt, V; Mossong, J; Zachariah, R; Inwani, C; Farah, B; Robert, I; Waelbrouck, A; Fonck, K; Médecins Sans Frontières, Mission Kenya, Brussels Operational Centre, Brussels, Belgium. (2007-01)
      A study was conducted among patients attending a public health centre in Nairobi, Kenya in order to (a) verify the prevalence of HIV, (b) identify clinical risk factors associated with HIV and (c) determine clinical markers for clinical screening of HIV infection at the health centre level. Of 304 individuals involved in the study,107(35%) were HIV positive. A clinical screening algorithm based on four clinical markers, namely oral thrush, past or present TB, past or present herpes zoster and prurigo would pick out 61 (57%) of the 107 HIV-positive individuals. In a resource-poor setting, introducing a clinical screening algorithm for HIV at the health centre level could provide an opportunity for targeting voluntary counselling and HIV testing, and early access to a range of prevention and care interventions.
    • Community support is associated with better antiretroviral treatment outcomes in a resource-limited rural district in Malawi.

      Zachariah, R; Teck, R; Buhendwa, L; Fitzgerald, M; Labana, S; Chinji, C; Humblet, P; Harries, A D; Médecins Sans Frontières, Medical Department (Operational Research), Brussels Operational Center, 68 Rue de Gasperich, L-1617, Luxembourg, Belgium. zachariah@internet.lu (Elsevier, 2007-01)
      A study was carried in a rural district in Malawi among HIV-positive individuals placed on antiretroviral treatment (ART) in order to verify if community support influences ART outcomes. Standardized ART outcomes in areas of the district with and without community support were compared. Between April 2003 (when ART was started) and December 2004 a total of 1634 individuals had been placed on ART. Eight hundred and ninety-five (55%) individuals were offered community support, while 739 received no such support. For all patients placed on ART with and without community support, those who were alive and continuing ART were 96 and 76%, respectively (P<0.001); death was 3.5 and 15.5% (P<0.001); loss to follow-up was 0.1 and 5.2% (P<0.001); and stopped ART was 0.8 and 3.3% (P<0.001). The relative risks (with 95% CI) for alive and on ART [1.26 (1.21-1.32)], death [0.22 (0.15-0.33)], loss to follow-up [0.02 (0-0.12)] and stopped ART [0.23 (0.08-0.54)] were all significantly better in those offered community support (P<0.001). Community support is associated with a considerably lower death rate and better overall ART outcomes. The community might be an unrecognized and largely 'unexploited resource' that could play an important contributory role in countries desperately trying to scale up ART with limited resources.
    • Conceptions of Agency and Constraint for HIV-Positive Patients and Healthcare Workers to Support Long-Term Engagement With Antiretroviral Therapy Care in Khayelitsha, South Africa

      Stern, E; Colvin, C; Gxabagxaba, N; Schutz, C; Burton, R; Meintjes, G (Taylor & Francis, 2017-03-01)
      In the context of the optimism around antiretroviral therapy (ART) as prevention of HIV/AIDS, addressing the barriers to long-term ART adherence is critical. This is particularly important given the tendency to individualise or use a blame discourse when exploring why HIV-infected patients "fail" to adequately adhere to ART, and not sufficiently exploring contextual reasons for poor adherence that may require varying solutions. This study took place at three clinics and one hospital in Khayelitsha, South Africa, to document the contextual factors that challenged ART adherence in this community. Interviews were conducted with 20 HIV-infected patients who had defaulted on their ART and were subsequently admitted to Khayelitsha hospital for clinical complications, and 9 ART service providers including doctors, nurses and HIV counsellors. Interviews assessed the reasons patients defaulted on ART and explored ways this could be prevented. Data from both groups were analysed collectively using thematic analysis. While the interviews revealed a landscape of environmental risks threatening adherence to ART, all patients managed to overcome the identified barriers at some point in their treatment phase, indicating the fluidity of patients' needs and decision making. Patients reported that distrustful relationships with service providers could inhibit their understanding of ART and/or interrupt their follow-up at clinics. Patients described their rationale and agency underlying non-adherence, such as testing their bodies' physical limits without ART medication. The study speaks to the need to appreciate contextual social and structural barriers related to ART adherence, and how these are negotiated differently by specific sub-groups, to support an appropriate response. It is imperative to not solely emphasise loss to follow-up but also assess patients' subjective trajectory of their ART journey, decision making and agency with adhering to ART, their relations with healthcare workers, and how these dynamics are intertwined with broader constraints in health systems.
    • Cost and cost-effectiveness of switching from d4T or AZT to a TDF-based first-line regimen in a resource-limited setting in rural Lesotho

      Jouquet, Guillaume; Bygrave, Helen; Kranzer, Katharina; Ford, Nathan; Gadot, Laurent; Lee, Janice; Hilderbrand, Katherine; Goemaere, Eric; Vlahakis, Natalie; Trivino, Laura; Makakole, Lipontso; Cleary, Susan; Medecins Sans Frontieres, Morija, Lesotho; Department of Infectious and Tropical Diseases, Clinical Research Unit, London School of Hygiene and Tropical Medicine, UK; Medecins Sans Frontieres, Cape Town, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Medecins Sans Frontieres, Geneva, Switzerland; Scott Hospital, Morija, Lesotho; Health Economics Unit, University of Cape Town, South Africa (Lippincott Williams & Wilkins, 2011-11-01)
      Latest World Health Organization guidelines recommend shifting away from Stavudine (d4T)-based regimens due to severe side effects. However, widespread replacement of d4T by Tenofovir (TDF) or Zidovudine (AZT) is hampered by cost concerns.
    • Development of dual-class antiretroviral drug resistance in a child coinfected with HIV and tuberculosis: a case report from KwaZulu-Natal, South Africa.

      Murphy, R A; France, H; Sunpath, H; Gordon, M L; Marconi, V; Kuritzkes, D R; McIntosh, K; Massachusetts General Hospital, and Brigham and Women's Hospital, Boston, MA, USA. richard.murphy@newyork.msf.org (Published by Oxford University Press, 2009-02)
      The treatment of concurrent HIV and tuberculosis (TB) in children <3 years of age has not been well-studied and is complicated by potential drug-drug interactions. The recommended antiretroviral therapy (ART) in coinfected children in South Africa consists of full-strength ritonavir, lamivudine and stavudine. We report on a child initiated on this regimen, during concurrent TB treatment, who promptly developed an adverse reaction, virologic failure and dual-class antiretroviral drug resistance, compromising subsequent salvage ART.
    • Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

      Singh, Ashika; Sunpath, Henry; Green, Taryn N; Padayachi, Nagavelli; Hiramen, Keshni; Lie, Yolanda; Anton, Elizabeth D; Murphy, Richard; Reeves, Jacqueline D; Kuritzkes, Daniel R; Ndung'u, Thumbi; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; McCord Hospital, Durban, KwaZulu-Natal, South Africa; Monogram Biosciences Inc., South San Francisco, CA, United States of America; Operational Support Unit, Doctors Without Borders, New York, USA; Section of Retroviral Therapeutics, Brigham and Women's Hospital, Boston, USA; Harvard Medical School, Boston, Massachusetts, USA (Lippincott Williams & Wilkins, 2011-11-01)
      Drug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy.
    • Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

      Blanc, F-X; Sok, T; Laureillard, D; Borand, L; Rekacewicz, C; Nerrienet, E; Madec, Y; Marcy, O; Chan, S; Prak, N; Kim, C; Lak, K K; Hak, C; Dim, B; Sin, C I; Sun, S; Guillard, B; Sar, B; Vong, S; Fernandez, M; Fox, L; Delfraissy, J-F; Goldfeld, A E; Pneumology Unit, Internal Medicine Department, Bicêtre Hospital, Assistance Publique–Hôpitaux de Paris, Le Kremlin-Bicêtre, France. xavier.blanc@bct.aphp.fr (2011-10-20)
      Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
    • Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

      Fenner, Lukas; Brinkhof, Martin W G; Keiser, Olivia; Weigel, Ralf; Cornell, Morna; Moultrie, Harry; Prozesky, Hans; Technau, Karl; Eley, Brian; Vaz, Paula; Pascoe, Margaret; Giddy, Janet; Van Cutsem, Gilles; Wood, Robin; Egger, Matthias; Davies, Mary-Ann; Institute of Social and Preventive Medicine, University of Bern, Switzerland. lfenner@ispm.unibe.ch (2010-08-15)
      BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.
    • Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

      Janssens, B; Raleigh, B; Soeung, S; Akao, K; Te, V; Gupta, J; Vun, M; Ford, N; Nouhin, J; Nerrienet, E; Médecins Sans Frontières, Phnom Penh, Cambodia. b.janssens@bigfoot.com (2007-11)
      OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.
    • Evaluation of a 5-year programme to prevent mother-to-child transmission of HIV infection in Northern Uganda

      Ahoua, Laurence; Ayikoru, Harriet; Gnauck, Katherine; Odaru, Grace; Odar, Emmanuel; Ondoa-Onama, Christine; Pinoges, Loretxu; Balkan, Suna; Olson, David; Pujades-Rodríguez, Mar; Epicentre, Paris, France; Medecins Sans Frontieres, Kampala, Uganda; Arua Regional District Hospital, Ministry of Health, Arua, Uganda; Medecins Sans Frontieres, Paris, France (2010-07-13)
      Prevention of mother-to-child transmission (PMTCT) is essential in HIV/AIDS control. We analysed 2000-05 data from mother-infant pairs in our PMTCT programme in rural Uganda, examining programme utilization and outcomes, HIV transmission rates and predictors of death or loss to follow-up (LFU). Out of 19,017 women, 1,037 (5.5%) attending antenatal care services tested HIV positive. Of these, 517 (50%) enrolled in the PMTCT programme and gave birth to 567 infants. Before tracing, 303 (53%) mother-infant pairs were LFU. Reasons for dropout were infant death and lack of understanding of importance of follow-up. Risk of death or LFU was higher among infants with no or incomplete intrapartum prophylaxis (OR = 1.90, 95% CI 1.07-3.36) and of weaning age <6 months (OR 2.55, 95% CI 1.42-4.58), and lower in infants with diagnosed acute illness (OR 0.30, 95% CI 0.16-0.55). Mother-to-child HIV cumulative transmission rate was 8.3%, and 15.5% when HIV-related deaths were considered. Improved tracking of HIV-exposed infants is needed in PMTCT programmes where access to early infant diagnosis is still limited.