• A Drug Dosage Table is a Useful Tool to Facilitate Prescriptions of Antiretroviral Drugs for Children in Thailand.

      Ponnet, M; Frederix, K; Petdachai, W; Wilson, D; Eksaengsri, A; Zachariah, R; Médecins Sans Frontières, Bangkok, Thailand. (2005-06)
      Scaling up of antiretroviral treatment (ART) for children in countries like Thailand will require decentralization and management by non-specialist doctors. We describe (a) the formulation of a standardized drug dosage table to facilitate antiretroviral drug (ARV) prescriptions for children, (b) the acceptability of such a table among doctors and (c) the safety and efficacy of drug doses in the table. Acceptability was assessed using a questionnaire. Safety and efficacy were assessed on the basis of incidence of adverse effects and virological response to treatment, respectively. Of all doctors (n=18), 17 (94%) found that the table was practical to use, avoided miscalculations and made them more confident with prescriptions. Of 49 children prescribed ARVs, less than 5% had adverse side-effects. All ARV-naïve children achieved undetectable viral loads within six months of ART. In our setting, a standardized drug dosage table provided a simple and reliable tool that facilitated ARV prescriptions for children.
    • Acceptance of anti-retroviral therapy among patients infected with HIV and tuberculosis in rural Malawi is low and associated with cost of transport.

      Zachariah, R; Harries, A D; Manzi, M; Gomani, P; Teck, R; Philips, M; Firmenich, P; Medecins sans Frontieres, Medical Department (Operational Research), Brussels Operational Center, Brussels, Belgium. zachariah@internet.lu (Public Library of Science, 2006)
      BACKGROUND: A study was conducted among newly registered HIV-positive tuberculosis (TB) patients systematically offered anti-retroviral treatment (ART) in a district hospital in rural Malawi in order to a) determine the acceptance of ART b) conduct a geographic mapping of those placed on ART and c) examine the association between "cost of transport" and ART acceptance. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cross-sectional analysis was performed on routine program data for the period of February 2003 to July 2004. Standardized registers and patient cards were used to gather data. The place of residence was used to determine road distances to the Thyolo district hospital. Cost of transport from different parts of the district was based on the known cost for public transport to the road-stop closest to the patient's residence. Of 1,290 newly registered TB patients, 1,003(78%) underwent HIV-testing of whom 770 (77%) were HIV-positive. 742 of these individuals (pulmonary TB = 607; extra-pulmonary TB = 135) were considered eligible for ART of whom only 101(13.6%) accepted ART. Cost of transport to the hospital ART site was significantly associated with ART acceptance and there was a linear trend in association between cost and ART acceptance (chi(2) for trend = 25.4, P<0.001). Individuals who had to pay 50 Malawi Kwacha (1 United States Dollar = 100 Malawi Kwacha, MW) or less for a one-way trip to the Thyolo hospital were four times more likely to accept ART than those who had to pay over 100 MW (Adjusted Odds ratio = 4.0, 95% confidence interval: 2.0-8.1, P<0.001). CONCLUSIONS/SIGNIFICANCE: ART acceptance among TB patients in a rural district in Malawi is low and associated with cost of transport to the centralized hospital based ART site. Decentralizing the ART offer from the hospital to health centers that are closer to home communities would be an essential step towards reducing the overall cost and burden of travel.
    • Access to CD4 Testing for Rural HIV Patients: Findings from a Cohort Study in Zimbabwe

      Vogt, Florian; Tayler-Smith, Katie; Bernasconi, Andrea; Makondo, Eliphas; Taziwa, Fabian; Moyo, Buhlebenkosi; Havazvidi, Liberty; Satyanarayana, Srinath; Manzi, Marcel; Khogali, Mohammed; et al. (Public Library of Science, 2015-06-17)
      CD4 cell count measurement remains an important diagnostic tool for HIV care in developing countries. Insufficient laboratory capacity in rural Sub-Saharan Africa is frequently mentioned but data on the impact at an individual patient level are lacking. Urban-rural discrepancies in CD4 testing have not been quantified to date. Such evidence is crucial for public health planning and to justify new yet more expensive diagnostic procedures that could circumvent access constraints in rural areas.
    • Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - The IeDEA Southern Africa Collaboration.

      Davies, Mary-Ann; Boulle, Andrew; Eley, Brian; Moultrie, Harry; Technau, Karl; Rabie, Helena; van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Egger, Matthias; et al. (2011-08-11)
      Objectives  To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART). Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment. Results  Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008). Conclusion  Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.
    • Adapting a community-based ART delivery model to the patients' needs: a mixed methods research in Tete, Mozambique

      Rasschaert, Freya; Decroo, Tom; Remartinez, Daniel; Telfer, Barbara; Lessitala, Faustino; Biot, Marc; Candrinho, Baltazar; Van Damme, Wim (BioMed Central, 2014-04)
      To improve retention in antiretroviral therapy (ART), lessons learned from chronic disease care were applied to HIV care, providing more responsibilities to patients in the care of their chronic disease. In Tete--Mozambique, patients stable on ART participate in the ART provision and peer support through Community ART Groups (CAG). This article analyses the evolution of the CAG-model during its implementation process.
    • 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.
    • Adherence to antiretroviral therapy: supervision or support?

      Mills, Edward J; Lester, Richard; Ford, Nathan; Faculty of Health Sciences, University of Ottawa, Ottawa, Canada; Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada; Médecins Sans Frontiers, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa (Elsevier, 2012-02)
      We are entering a new phase in the strategic use of antiretroviral drugs. In addition to dramatically reducing HIV/AIDS-related morbidity and mortality, these drugs have recently shown an important effect in reducing HIV incidence and transmission.
    • Adherence to HIV post-exposure prophylaxis in victims of sexual assault: a systematic review and meta-analysis

      Chacko, Liza; Ford, Nathan; Sbaiti, Mariam; Siddiqui, Ruby; Imperial College London, St Mary's Hospital, London, UK; Médecins Sans Frontières, Doctors without Borders (MSF-UK), London, UK; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa (BMJ Publishing Group, 2012-02-13)
      ObjectiveTo assess adherence to post-exposure prophylaxis (PEP) for the prevention of HIV infection in victims of sexual assault.MethodsThe authors carried out a systematic review, random effects meta-analysis and meta-regression of studies reporting adherence to PEP among victims of sexual violence. Seven electronic databases were searched. Our primary outcome was adherence; secondary outcomes included defaulting, refusal and side effects.Results2159 titles were screened, and 24 studies matching the inclusion criteria were taken through to analysis. The overall proportion of patients adhering to PEP (23 cohort studies, 2166 patients) was 40.3% (95% CI 32.5% to 48.1%), and the overall proportion of patients defaulting from care (18 cohorts, 1972 patients) was 41.2% (95% CI 31.1% to 51.4%). Adherence appeared to be higher in developing countries compared with developed countries.ConclusionsAdherence to PEP is poor in all settings. Interventions are needed to support adherence.
    • 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.
    • AIDS Review

      Harries, A D; Zachariah, R (2010-01)
    • AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa.

      Chu, Kathryn M; Mahlangeni, Gcina; Swannet, Sarah; Ford, Nathan P; Boulle, Andrew; Van Cutsem, Gilles; Médecins Sans Frontières, Braamfontein, Johannesburg, South Africa. kathryn.chu@joburg.msf.org (2010-07)
      BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality. Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential.
    • AIDS: patent rights versus patient's rights.

      Chirac, P; von Schoen-Angerer, T; Kasper, T; Ford, N; Médecins Sans Frontières, Paris, France. (Elsevier, 2000-08-05)
    • Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome

      Monaco, CL; Gootenberg, DB; Zhao, G; Handley, SA; Ghebremichael, MS; Lim, ES; Lankowski, A; Baldridge, MT; Wilen, CB; Flagg, M; et al. (Elsevier - We regret that this article is behind a paywall., 2016-03-09)
      Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.
    • Antiretroviral drug supply challenges in the era of scaling up ART in Malawi

      Schouten, Erik J; Jahn, Andreas; Ben-Smith, Anne; Makombe, Simon D; Harries, Anthony D; Aboagye-Nyame, Francis; Chimbwandira, Frank (2011)
    • Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression

      Musinguzi, N; Castillo-Mancilla, J; Morrow, M; Byakwaga, H; Mawhinney, S; Burdo, TH; Boum, Y; Muzoora, C; Bwana, BM; Siedner, MJ; et al. (Lippincott, Williams & Wilkins, 2019-12-01)
      Background: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. Setting: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. Methods: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8+ T-cell activation (HLA-DR+/CD38+ coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. Results: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR+/CD8+ (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. Conclusions: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.
    • Antiretroviral therapy and early mortality in South Africa.

      Boulle, A; Bock, P; Osler, M; Cohen, K; Channing, L; Hilderbrand, K; Mothibi, E; Zweigenthal, V; Slingers, N; Cloete, K; et al. (Wolrd Health Organization, 2008-09)
      OBJECTIVE: To describe province-wide outcomes and temporal trends of the Western Cape Province antiretroviral treatment (ART) programme 5 years since inception, and to demonstrate the utility of the WHO monitoring system for ART. METHODS: The treatment programme started in 2001 through innovator sites. Rapid scaling-up of ART provision began early in 2004, located predominantly in primary-care facilities. Data on patients starting ART were prospectively captured into facility-based registers, from which monthly cross-sectional activity and quarterly cohort reports were aggregated. Retention in care, mortality, loss to follow-up and laboratory outcomes were calculated at 6-monthly durations on ART. FINDINGS: By the end of March 2006, 16 234 patients were in care. The cohort analysis included 12 587 adults and 1709 children. Women accounted for 70% of adults enrolled. After 4 and 3 years on ART respectively, 72.0% of adults (95% confidence interval, CI: 68.0-75.6) and 81.5% (95% CI: 75.7-86.1) of children remained in care. The percentage of adults starting ART with CD4 counts less than 50 cells/microl fell from 51.3% in 2001 to 21.5% in 2005, while mortality at 6 months fell from 12.7% to 6.6%, offset in part by an increase in loss to follow-up (reaching 4.7% at 6 months in 2005). Over 85% of adults tested had viral loads below 400 copies/ml at 6-monthly durations until 4 years on ART. CONCLUSION: The location of care in primary-care sites in this programme was associated with good retention in care, while the scaling-up of ART provision was associated with reduced early mortality.
    • Antiretroviral therapy for HIV prevention: many concerns and challenges, but are there ways forward in sub-Saharan Africa?

      Zachariah, R; Harries, A D; Philips, M; Arnould, L; Sabapathy, K; O'Brien, D P; Ferreyra, C; Balkan, S; Médecins Sans Frontières, Medical Department (Operational Research), Brussels Operational Centre, Belgium. (2010-01-28)
      Scientists from the WHO have presented a theoretical mathematical model of the potential impact of universal voluntary HIV testing and counselling followed by immediate antiretroviral therapy (ART). The results of the model suggests that, in a generalised epidemic as severe as that in sub-Saharan Africa (SSA), HIV incidence may be reduced by 95% in 10 years and that this approach may be cost effective in the medium term. This offers a 'ray of hope' to those who have thus far only dreamed of curbing the HIV/AIDS epidemic in SSA, as until now the glaring truth has been pessimistic. When it comes to ART, approximately 7 of 10 people who clinically need ART still do not receive it. From an epidemic point of view, for every person placed on ART an estimated four to six others acquire HIV. The likelihood of achieving the targets of the Millennium Development Goals for 2015 and universal ART access by 2010 are thus extremely low. A new window of opportunity may have now opened, but there are many unanswered feasibility and acceptability issues. In this paper, we highlight four key operational challenges linked to acceptability and feasibility and discuss possible ways forward to address them.
    • Antiretroviral Therapy in Primary Health Care: Experience of the Khayelitsha Programme in South Africa

      MSF South Africa, Dept of Public Health at University of Cape Town; Provincial Administration of the Western Cape, South Africa; World Health Organization (WHO, 2003)
    • Antiretroviral Therapy outcomes among adolescents and youth in rural Zimbabwe

      Bygrave, Helen; Mtangirwa, Judith; Ncube, Kwenzakwenkosi; Ford, Nathan; Kranzer, Katharina; Munyaradzi, Dhodho; Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa. Helen.bygrave@joburg.msf.org (2012-12-20)
      Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.