• Risk factors and mortality associated with resistance to first line antiretroviral therapy: multicentric cross-sectional and longitudinal analyses

      Pinoges, Loretxu; Schramm, Birgit; Poulet, Elisabeth; Balkan, Suna; Szumilin, Elisabeth; Ferreyra, Cecilia; Pujades-Rodríguez, M (Lippincott Williams & Wilkins, 2015-01-12)
      Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management.
    • Risk Factors for High Early Mortality in Patients on Antiretroviral Treatment in a Rural District of Malawi.

      Zachariah, R; Fitzgerald, M; Massaquoi, M; Pasulani, O; Arnould, L; Makombe, S D; Harries, A D; Medecins sans Frontieres, Operational Research, Brussels Operational Center, Belgium. zachariah@internet.lu (2006-11-28)
      OBJECTIVES: Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. DESIGN AND SETTING: A cross-sectional analytical study set in Thyolo district, Malawi. METHODS: Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. RESULTS: A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P
    • Risk Factors for Mortality During Antiretroviral Therapy in Older Populations in Resource-Limited Settings

      O'Brien, D; Spelman, T; Greig, J; McMahon, J; Ssonko, C; Casas, E; Mesic, A; Du Cros, P; Ford, N (International AIDS Society, 2016-01-14)
      An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population.
    • Risk factors for mortality in AIDS-associated Kaposi sarcoma in a primary care antiretroviral treatment program in Malawi

      Chu, Kathryn; Misinde, Dalitso; Massaquoi, Moses; Pasulani, Olesi; Mwagomba, Beatrice; Ford, Nathan; Zachariah, Rony (2010-04)
    • Risk Factors for Unstructured Treatment Interruptions and Association with Survival in Low to Middle Income Countries

      McMahon, JH; Spelman, T; Ford, N; Greig, J; Mesic, A; Ssonko, C; Casas, EC; O'Brien, DP (BioMed Central, 2016-07-11)
      Antiretroviral therapy (ART) treatment interruptions lead to poor clinical outcomes with unplanned or unstructured TIs (uTIs) likely to be underreported. This study describes; uTIs, their risk factors and association with survival.
    • Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

      Ahoua, L; Guenther, G; Pinoges, L; Anguzu, P; Chaix, M L; Le Tiec, C; Balkan, S; Olson, D; Olaro, C; Pujades-Rodriguez, M; et al. (2009-06-03)
      ABSTRACT: BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/mL) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n=701) and 70% (n=369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/mL). Risk factors for virological failure (>1,000 copies/mL) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSIONS: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.
    • Risk of death among those awaiting treatment for HIV infection in Zimbabwe: adolescents are at particular risk

      Shroufi, Amir; Ndebele, Wedu; Nyathi, Mary; Gunguwo, Hilary; Dixon, Mark; Saint-Sauveur, Jean F; Taziwa, Fabian; Viñoles, Mari C; Ferrand, Rashida A (International AIDS Society, 2015-02-23)
      Mortality among HIV-positive adults awaiting antiretroviral therapy (ART) has previously been found to be high. Here, we compare adolescent pre-ART mortality to that of adults in a public sector HIV care programme in Bulawayo, Zimbabwe.
    • Routine immediate eye examination at the point of care for diagnosis of AIDS-related Cytomegalovirus Retinitis among patients with a CD4-count < 100 in Myanmar

      Ei, WLSS; Soe, KP; Hilbig, A; Murray, J; Heiden, D (Oxford University Press, 2019-06-14)
      A retrospective review of diagnosis of cytomegalovirus retinitis (CMVR) before and after introduction of routine immediate eye examination among AIDS patient in Myanmar with an absolute CD4 T cell count <100 cells/microliter demonstrated an increased detection of CMVR from 1.1% (14/1233) to 10.7% (65/608), an improvement of approximately ten-fold. Diagnosis of CMVR was achieved a mean of 2 days after clinic enrollment.
    • Safety of efavirenz in first-trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational cohorts.

      Ford, Nathan; Mofenson, Lynne; Kranzer, Katharina; Medu, Lanre; Frigati, Lisa; Mills, Edward J; Calmy, Alexandra; Médecins Sans Frontières, South Africa Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa cPediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA dLondon School of Hygiene and Tropical Medicine, London, UK eFaculty of Health Sciences, Simon Fraser University, Vancouver, Canada fRed Cross Children's hospital, Cape Town, South Africa gFaculty of Health Sciences, University of Ottawa, Canada hGeneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland. (2010-05-14)
      INTRODUCTION
    • Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis

      Ford, Nathan; Calmy, Alexandra; Mofenson, Lynne; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Médecins Sans Frontières, Geneva, Switzerland; Geneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland; Pediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA (Lippincott Williams & Wilkins, 2011-11-28)
      Evidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39).
    • Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

      Ford, Nathan; Lee, Janice; Andrieux-Meyer, Isabelle; Calmy, Alexandra; Médecins Sans Frontières, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; Service of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland (DovePress, 2011-04-28)
      The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2-4 events was lower for rilpivirine compared with efavirenz. Grade 3-4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs.
    • Safety, Feasibility, and Acceptability of the PrePex Device for Adult Male Circumcision in Malawi

      Kohler, PK; Tippett Barr, BA; Kangʼombe, A; Hofstee, C; Kilembe, F; Galagan, S; Chilongozi, D; Namate, D; Machaya, M; Kabwere, K; et al. (Lippincott Williams & Wilkins, 2016-06-01)
      Nonsurgical adult male circumcision devices present an alternative to surgery where health resources are limited. This study aimed to assess the safety, feasibility, and acceptability of the PrePex device for adult male circumcision in Malawi.
    • SAMBA HIV semi-quantitative test, a new point-of-care viral load monitoring assay for resource-limited settings

      Ritchie, Allyson V; Ushiro-Lumb, Ines; Edemaga, Daniel; Joshi, Hrishikesh A; De Ruiter, Annemiek; Szumilin, Elisabeth; Jendrulek, Isabelle; McGuire, Megan; Goel, Neha; Sharma, Pia I; et al. (2014-07-16)
      Routine viral load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA Semi-Q Test in London, Malawi, and Uganda. The SAMBA HIV-1 Semi-Q Test can distinguish between patients with VL above or below 1000 copies/ml. The SAMBA Semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA Semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0. Testing of 96 2-10 fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda, respectively, yielded an overall accuracy for SAMBA Semi-Q of 99% (95% CI 93.8 - 99.9%) and 96.9% (95% CI 94.9 - 98.3%) respectively compared to Roche. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cut-off of 1000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral load of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control defined as either <1000 copies/ml (SAMBA cut-off) or <5000 copies/ml (WHO 2010 criterion). This study suggests that SAMBA Semi-Q has adequate concurrency with the gold standard measurements for viral load measurement. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings.
    • Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges

      Roberts, T; Cohn, J; Bonner, K; Hargreaves, S (Oxford University Press, 2016-04-15)
      Despite immense progress in antiretroviral therapy (ART) scale-up, many people still lack access to basic standards of care, with our ability to meet the Joint United Nations Programme on HIV/AIDS 90-90-90 treatment targets for HIV/AIDS dependent on dramatic improvements in diagnostics. The World Health Organization recommends routine monitoring of ART effectiveness using viral load (VL) testing at 6 months and every 12 months, to monitor treatment adherence and minimize failure, and will publish its VL toolkit later this year. However, the cost and complexity of VL is preventing scale-up beyond developed countries and there is a lack of awareness among clinicians as to the long-term patient benefits and its role in prolonging the longevity of treatment programs. With developments in this diagnostic field rapidly evolving-including the recent improvements for accurately using dried blood spots and the imminent appearance to the market of point-of-care technologies offering decentralized diagnosis-we describe current barriers to VL testing in resource-limited settings. Effective scale-up can be achieved through health system and laboratory system strengthening and test price reductions, as well as tackling multiple programmatic and funding challenges.
    • Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries.

      Zachariah, R; Harries, A D; Luo, C; Bachman, G; Graham, S M; Médecins Sans Frontières, Medical department (Operational Research), Brussels Operational Center, Brussels, Belgium. zachariah@internet.lu (Elsevier, 2007-10)
      Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available antibiotic that substantially reduces HIV-related morbidity and mortality in both adults and children. Prophylaxis with co-trimoxazole is a recommended intervention of proven benefit that could serve not only as an initial step towards improving paediatric care in young children with limited access to antiretroviral treatment, but also as an important complement to antiretroviral therapy in resource-limited settings. Despite co-trimoxazole's known clinical benefits, the potential operational benefits, and favourable recommendations by WHO, UNAIDS, and UNICEF, its routine use in developing countries--particularly sub-Saharan Africa--has remained limited. Out of an estimated 4 million children in need of co-trimoxazole prophylaxis (HIV-exposed and HIV-infected), only 4% are currently receiving this intervention. We discuss some of the major barriers preventing the scale-up of co-trimoxazole prophylaxis for children in countries with a high prevalence of HIV and propose specific actions required to tackle these challenges.
    • Screening and treating cervical cancer in HIV-positive women in Cambodia.

      Raguenaud, Marie-Eve; Isaakidis, Petros; Ping, Chutema; Reid, Tony (2009-08-15)
    • Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in Southern Africa: analysis of cohort studies at antiretroviral treatment programmes

      Ballif, M; Zürcher, K; Reid, SE; Boulle, A; Fox, MP; Prozesky, HW; Chimbetete, C; Zwahlen, M; Egger, M; Fenner, L (BMJ Publishing Group, 2018-01-11)
      Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa.
    • Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

      Pujades-Rodriguez, M; O'Brien, D; Humblet, P; Calmy, A; Epicentre, Paris, France; Médecins Sans Frontières, Paris, France; Campaign for Access to Essential Medicines, Geneva, Switzerland (2008-07-11)
      OBJECTIVES: To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. DESIGN/METHODS: We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. RESULTS: Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. CONCLUSION: The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.