• 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; et al. (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; et al. (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.
    • 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.
    • Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

      Harries, Anthony D; Zachariah, Rony; van Oosterhout, Joep J; Reid, Steven D; Hosseinipour, Mina C; Arendt, Vic; Chirwa, Zengani; Jahn, Andreas; Schouten, Erik J; Kamoto, Kelita; et al. (2010-01)
      Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings.
    • 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; et al. (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.
    • 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; et al. (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.
    • Growth in Virologically Suppressed HIV-Positive Children on Antiretroviral Therapy: Individual and Population-level References.

      Keiser, Olivia; Blaser, Nello; Davies, Mary-Ann; Wessa, Patrick; Eley, Brian; Moultrie, Harry; Rabie, Helena; Technau, Karl-Günther; Ndirangu, James; Garone, Daniela; et al. (2015-10)
      Combination antiretroviral therapy (ART) suppresses viral replication in HIV-infected children. The growth of virologically suppressed children on ART has not been well documented. We aimed to develop dynamic reference curves for weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ).
    • HIV Viral Load Monitoring in Resource-Limited Regions: Optional or Necessary?

      Calmy, A; Ford, N; Hirschel, B; Reynolds, S; Lynen, L; Goemaere, E; Garcia de la Vega, F; Perrin, L; Rodriguez, W; Medecins sans Frontieres, Access to Medicines Campaign, Geneva, 1211, Switzerland. acalmy@gmail.com (Published by: Infectious Diseases Society of America, 2007-01-01)
      Although it is a standard practice in high-income countries, determination of the human immunodeficiency virus (HIV) load is not recommended in developing countries because of the costs and technical constraints. As more and more countries establish capacity to provide second-line therapy, and as costs and technological constraints associated with viral load testing decrease, the question of whether determination of the viral load is necessary deserves attention. Viral load testing could increase in importance as a guide for clinical decisions on when to switch to second-line treatment and on how to optimize the duration of the first-line treatment regimen. In addition, the viral load is a particularly useful tool for monitoring adherence to treatment, performing sentinel surveillance, and diagnosing HIV infection in children aged <18 months. Rather than considering viral load data to be an unaffordable luxury, efforts should be made to ensure that viral load testing becomes affordable, simple, and easy to use in resource-limited settings.
    • Loss of correlation between HIV viral load and CD4+ T-cell counts in HIV/HTLV-1 co-infection in treatment naive Mozambican patients

      Bhatt, N B; Gudo, E S; Semá, C; Bila, D; Di Mattei, P; Augusto, O; Garsia, R; Jani, I V; Department of Immunology, Instituto Nacional de Saúde, Maputo, Mozambique; HIV Outpatient Clinic, Alto Mae Health Centre, Medecins Sans Frontieres, Switzerland, Maputo, Mozambique; Department of Medicine, University of Sydney, New South Wales, Australia;Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia (2009-12-01)
      Seven hundred and four HIV-1/2-positive, antiretroviral therapy (ART) naïve patients were screened for HTLV-1 infection. Antibodies to HTLV-1 were found in 32/704 (4.5%) of the patients. Each co-infected individual was matched with two HIV mono-infected patients according to World Health Organization clinical stage, age +/-5 years and gender. Key clinical and laboratory characteristics were compared between the two groups. Mono-infected and co-infected patients displayed similar clinical characteristics. However, co-infected patients had higher absolute CD4+ T-cell counts (P = 0.001), higher percentage CD4+ T-cell counts (P < 0.001) and higher CD4/CD8 ratios (P < 0.001). Although HIV plasma RNA viral loads were inversely correlated with CD4+ T-cell-counts in mono-infected patients (P < 0.0001), a correlation was not found in co-infected individuals (P = 0.11). Patients with untreated HIV and HTLV-1 co-infection show a dissociation between immunological and HIV virological markers. Current recommendations for initiating ART and chemoprophylaxis against opportunistic infections in resource-poor settings rely on more readily available CD4+ T-cell counts without viral load parameters. These guidelines are not appropriate for co-infected individuals in whom high CD4+ T-cell counts persist despite high HIV viral load states. Thus, for co-infected patients, even in resource-poor settings, HIV viral loads are likely to contribute information crucial for the appropriate timing of ART introduction.
    • Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

      van Zyl, Gert Uves; van Mens, Thijs E; McIlleron, Helen; Zeier, Michele; Nachega, Jean B; Decloedt, Eric; Malavazzi, Carolina; Smith, Peter; Huang, Yong; van der Merwe, Lize; et al. (2011-04)
      In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.
    • Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate?

      Arnedo, M; Alonso, E; Eisenberg, N; Ibáñez, L; Ferreyra, C; Jaén, A; Flevaud, L; Khamadi, S; Roddy, P; Gatell, JM; et al. (Public Library of Science, 2012-12-06)
      Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate.
    • Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda

      Mills, Edward J; Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Chan, Keith; Ford, Nathan; Hogg, Robert S; Cooper, Curtis; Faculty of Health Sciences, University of Ottawa, Ottawa, Canada; The AIDS Support Organization (TASO), Headquarters, Kampala, Uganda; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada; Médecins Sans Frontiers (MSF), Geneva, Switzerland; Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada (Lippincott Williams & Wilkins, 2011-03-27)
      Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda.
    • Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

      Coetzee, D; Hildebrand, K; Boulle, A; Maartens, G; Louis, F; Labatala, V; Reuter, H; Ntwana, N; Goemaere, E; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa. (2004-04-09)
      BACKGROUND: A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. METHODS: Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. RESULTS: Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. CONCLUSIONS: ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.
    • Outcomes After Virologic Failure of First-Line ART in South Africa

      Murphy, Richard A; Sunpath, Henry; Lu, Zhigang; Chelin, Neville; Losina, Elena; Gordon, Michelle; Ross, Douglas; Ewusi, Aba D; Matthews, Lynn T; Kuritzkes, Daniel R; et al. (2010-04-24)
      To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART).
    • Outcomes and safety of concomitant nevirapine and rifampicin treatment under programme conditions in Malawi.

      Moses, M; Zachariah, R; Tayler-Smith, K; Misinde, D; Foncha, C; Manzi, M; Bauerfeind, A; Mwagomba, B; Kwanjana, J; Harries, A D; et al. (2010-02)
      SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: To report on 1) clinical, immunological and virological outcomes and 2) safety among human immunodeficiency virus (HIV) infected patients with tuberculosis (TB) who received concurrent nevirapine (NVP) and rifampicin (RMP) based treatment. DESIGN: Retrospective cohort study. METHODS: Analysis of programme data, June-December 2007. RESULTS: Of a total of 156 HIV-infected TB patients who started NVP-based antiretroviral treatment, 136 (87%) completed TB treatment successfully, 16 (10%) died and 5 (4%) were transferred out. Mean body weight and CD4 gain (adults) were respectively 4.4 kg (95%CI 3.3-5.4) and 140 cells/mm(3) (95%CI 117-162). Seventy-four per cent of patients who completed TB treatment and had a viral load performed (n = 74) had undetectable levels (<50 copies/ml), while 17 (22%) had a viral load of 50-1000 copies/ml. Hepatotoxicity was present in 2 (1.3%) patients at baseline. Two patients developed Grade 2 and one developed Grade 3 alanine transaminase enzyme elevations during TB treatment (incidence rate per 10 years of follow-up 4.2, 95%CI 1.4-13.1). There were no reported deaths linked to hepatotoxicity. CONCLUSIONS: In a rural district in Malawi, concomitant NVP and RMP treatment is associated with good TB treatment outcomes and appears safe. Further follow-up of patients would be useful to ascertain the longer-term effects of this concurrent treatment.
    • Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy

      Boulle, A; Van Cutsem, G; Cohen, K; Hilderbrand, K; Mathee, S; Abrahams, M; Goemaere, E; Coetzee, D; Maartens, G; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Médecins Sans Frontières, Cape Town, South Africa; Site B Community Health Centre, Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa (2008-08-06)
      CONTEXT: Rifampicin-based antitubercular therapy reduces the plasma concentrations of nevirapine and efavirenz. The virological consequences of these interactions are not well described. OBJECTIVE: To assess the effectiveness and tolerability of concomitant efavirenz- or nevirapine-based combination antiretroviral therapy and rifampicin-based antitubercular therapy. DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of prospectively collected routine clinical data in a community-based South African antiretroviral treatment program. Antiretroviral treatment-naive adults enrolled between May 2001 and June 2006 were included in the analysis, and were followed up until the end of 2006. INTERVENTIONS: Patients starting antiretroviral therapy with or without concurrent antitubercular therapy received either efavirenz or nevirapine at standard doses. Patients developing tuberculosis while taking antiretroviral therapy that included nevirapine were either changed to efavirenz or continued taking nevirapine. MAIN OUTCOME MEASURES: Viral load of 400 copies/mL or more after 6, 12, and 18 months of antiretroviral therapy; time to the first viral load of 400 copies/mL or more; time to confirmed virological failure (2 consecutive values > or = 5000 copies/mL); time to death; and time to treatment-limiting toxicity were assessed. RESULTS: The analysis included 2035 individuals who started antiretroviral therapy with efavirenz (1074 with concurrent tuberculosis) and 1935 with nevirapine (209 with concurrent tuberculosis). There were no differences in time to death or substitution of either antiretroviral drug for toxicity with and without concurrent tuberculosis. Patients starting nevirapine with concurrent tuberculosis were at a higher risk of elevated viral load most notably at 6 months (16.3%; 95% confidence interval [CI], 10.6%-23.5%) than those without tuberculosis (8.3%; 95% CI, 6.7%-10.0%; adjusted odds ratio [OR], 2.1; 95% CI, 1.2-3.4; and in the combined estimate, adjusted OR, 1.7; 95% CI, 1.2-2.6). In the time-to-event analysis of confirmed virological failure (2 consecutive values of > or = 5000 copies/mL), patients starting nevirapine with concurrent tuberculosis developed virological failure sooner (adjusted hazard ratio [HR] 2.2; 95% CI, 1.3-3.7). There were no differences between patients starting efavirenz with and without concurrent tuberculosis (adjusted OR, 1.1; 95% CI, 0.8-1.5 [combined estimate] and adjusted HR, 1.1; 95% CI, 0.6-2.0, respectively). There was no difference in time to virological rebound in patients free of tuberculosis and those developing tuberculosis during follow-up while taking nevirapine (adjusted HR, 1.0; 95% CI, 0.5-2.0) or efavirenz (adjusted HR, 0.8; 95% CI, 0.4-1.7). CONCLUSION: In this cohort study, virological outcomes were inferior when nevirapine-based antiretroviral therapy was commenced while taking antitubercular treatment (vs without concurrent tuberculosis) but comparable when starting efavirenz-based antiretroviral therapy (vs without concurrent tuberculosis) or when tuberculosis developed while taking established nevirapine- or efavirenz-based therapies.
    • Patient needs and point-of-care requirements for HIV load testing in resource-limited settings

      Usdin, Martine; Guillerm, Martine; Calmy, Alexandra; Medecins Sans Frontieres Access Campaign, Paris, France; University of Liverpool School of Public Health, Liverpool, United Kingdom; Department of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland (2010-04-15)
      Medecins Sans Frontieres (MSF) is an international, independent medical nongovernmental organization. One way in which MSF acts to improve patient care is to assist in the identification and development of adapted and appropriate tools for use in resource-limited settings. One strategy to achieve this goal is through active collaborations with scientists and developers, to make some of the field needs known and to help define the medical strategy behind the implementation of new diagnostic tests. Tests used in the field need to be effective in often extreme conditions and must also deliver high-quality, reliable results that can be used in the local context. In this article, we discuss some patient and health care provider needs for human immunodeficiency virus (HIV) load measurement in resource-limited settings. This is just one of the areas in which effective, quality tools are desperately needed, not only by MSF and other international nongovernmental organizations, but also by many other health service providers. We hope that, by clearly defining the needs of patients in MSF clinics-as well as we can assess this-and by explaining why these tools are needed, how they should perform, and how their results can be integrated into a program, we will encourage the development of such tools and hasten their implementation in areas where they are so urgently needed.
    • Promoting adherence to antiretroviral therapy: the experience from a primary care setting in Khayelitsha, South Africa.

      Coetzee, D; Boulle, A; Hildebrand, K; Asselman, V; Van Cutsem, G; Goemaere, E; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. dcoetzee@phfm.uct.ac.za (2004-06)
      OBJECTIVE: To describe the approach used to promote adherence to antiretroviral therapy (ART) and to present the outcomes in the first primary care public sector ART project in South Africa. DESIGN: The study is a prospective open cohort, including all adult patients naive to previous ART who received antiretroviral treatment in Khayelitsha, from May 2001 to the end of 2002. Patients were followed until their most recent visit before 31 July 2003. METHODS: Plasma viral load was determined at 3, 6, 12, 18 and 24 months after ART was initiated, and CD4 cell counts 6-monthly. Kaplan-Meier estimates were determined for the cumulative proportions of patients surviving, and patients with viral load suppression and viral rebound. RESULTS: A total of 287 patients were initiated on triple therapy. The probability of survival was 86.3% at 24 months. The median CD4 cell count gain was 288 cells/microliters at 24 months. Viral load was less than 400 copies/ml in 89.2, 84.2 and 69.7% of patients at 6, 12 and 24 months, respectively. The cumulative probability of viral rebound (two consecutive HIV-RNA measurements above 400 copies/ml) after achieving an HIV-RNA measurement below 400 copies/ml was 13.2% at 18 months. CONCLUSION: The study shows that, with a standard approach to patient preparation and strategies to enhance adherence, a cohort of patients on ART can be retained in a resource-limited setting in a developing country. A high proportion of patients achieved suppression of viral replication. The subsequent probability of viral rebound was low.
    • Public health. Getting HIV treatment to the most people.

      Lynch, Sharonann; Ford, Nathan; van Cutsem, Gilles; Bygrave, Helen; Janssens, Bart; Decroo, Tom; Andrieux-Meyer, Isabelle; Roberts, Teri; Balkan, Suna; Casas, Esther; et al. (2012-07-20)