• 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; Mwale, M; Msunguma, W; Reed, J; Chimbwandira, F (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; Allain, Jean-Pierre; Lee, Helen H (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.
    • Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

      Khan, Samsuddin; Das, Mrinalini; Andries, Aristomo; Deshpande, Alaka; Mansoor, Homa; Saranchuk, Peter; Isaakidis, Petros (Co-Action Publishing, 2014-07-30)
      There are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care.
    • Self-transfer and mortality amongst adults lost to follow-up in ART programmes in low and middle-income countries: systematic review and meta-analysis

      Wilkinson, Lynne S; Skordis-Worrall, Jolene; Ajose, Olawale; Ford, Nathan (Wiley-Blackwell, 2014-11-22)
      To ascertain estimates of adult patients, recorded as lost to follow-up (LTFU) within antiretroviral treatment (ART) programmes, who have self-transferred care, died or truly stopped ART in low- and middle-income countries.
    • Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa.

      Boulle, Andrew; Van Cutsem, Gilles; Hilderbrand, Katherine; Cragg, Carol; Abrahams, Musaed; Mathee, Shaheed; Ford, Nathan; Knight, Louise; Osler, Meg; Myers, Jonny; Goemaere, Eric; Coetzee, David; Maartens, Gary; School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Cape Town, South Africa. andrew.boulle@uct.ac.za (2010-02-20)
      OBJECTIVES: We report on outcomes after 7 years of a community-based antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death registry linkages to correct for mortality under-ascertainment. DESIGN: This is an observational cohort study. METHODS: Since inception, patient-level clinical data have been prospectively captured on-site into an electronic patient information system. Patients with available civil identification numbers who were lost to follow-up were matched with the national death registry to ascertain their vital status. Corrected mortality estimates weighted these patients to represent all patients lost to follow-up. CD4 cell count outcomes were reported conditioned on continuous virological suppression. RESULTS: Seven thousand, three hundred and twenty-three treatment-naive adults (68% women) started ART between 2001 and 2007, with annual enrolment increasing from 80 in 2001 to 2087 in 2006. Of 9.8% of patients lost to follow-up for at least 6 months, 32.8% had died. Corrected mortality was 20.9% at 5 years (95% confidence interval 17.9-24.3). Mortality fell over time as patients accessed care earlier (median CD4 cell count at enrolment increased from 43 cells/microl in 2001 to 131 cells/microl in 2006). Patients who remained virologically suppressed continued to gain CD4 cells at 5 years (median 22 cells/microl per 6 months). By 5 years, 14.0% of patients had failed virologically and 12.2% had been switched to second-line therapy. CONCLUSION: At a time of considerable debate about future global funding of ART programmes in resource-poor settings, this study has demonstrated substantial and durable clinical benefits for those able to access ART throughout this period, in spite of increasing loss to follow-up.
    • Severe hyperlactataemia complicating stavudine first-line antiretroviral therapy in South Africa.

      Stead, D; Osler, M; Boulle, A; Rebe, K; Meintjes, G; GF Jooste Hospital, Cape Town, South Africa. davestead@mweb.co.za (2008-11)
      BACKGROUND: In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T. METHODS: GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate. RESULTS: In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL. CONCLUSIONS: This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.
    • Sexually transmitted infections among prison inmates in a rural district of Malawi.

      Zachariah, R; Harries, A D; Chantulo, A; Yadidi, A E; Nkhoma, W; Maganga, O; Mission (Malawi), Medecins sans Frontieres-Luxembourg, 70 rue de Gasperich, L-1617, Luxembourg. zachariah@internet.lu (Elsevier, 2008-02-14)
      As part of a comprehensive human immunodeficiency virus (HIV) prevention strategy targeting high-risk groups, sexually transmitted infection (STI) clinics are offered to all prisoners in Thyolo district, southern Malawi. Prison inmates are not, however, allowed access to condoms as it is felt that such an intervention might encourage homosexuality which is illegal in Malawi. A study was conducted between January 2000 and December 2001 in order to determine the prevalence, incidence, and patterns of STIs among male inmates of 2 prisons in this rural district. A total of 4229 inmates were entered into the study during a 2-year period. Of these, 178 (4.2%) were diagnosed with an STI. This included 83 (46%) inmates with urethral discharge, 60 (34%) with genital ulcer disease (GUD), and 35 (20%) inmates with epididymo-orchitis. Fifty (28%) STIs were considered incident cases acquired within the prisons (incidence risk 12 cases/1000 inmates/year). GUD was the most common STI in this group comprising 52% of all STI. This study shows that a considerable proportion of STIs among inmates are acquired within prison. In a setting of same-sex inmates, this suggests inter-prisoner same-sex sexual activity. The findings have implications for HIV transmission and might help in developing more rational policies on STI control and condom access within Malawi prisons.
    • Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

      Rasschaert, Freya; Koole, Olivier; Zachariah, Rony; Lynen, Lut; Manzi, Marcel; Van Damme, Wim; Institute of Tropical Medicine, Nationale straat 155, Antwerpen 2000, Belgium. frasschaert@itg.be (2012-12)
      Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district).
    • Similar mortality and reduced loss to follow-up in integrated compared with vertical programs providing antiretroviral treatment in sub-saharan Africa.

      Greig, Jane; O'Brien, Daniel P; Ford, Nathan; Spelman, Tim; Sabapathy, Kalpana; Shanks, Leslie; Manson Unit, Médecins sans Frontières, Saffron Hill, London, UK. jane.greig@london.msf.org (2012-04-15)
      Vertical HIV programs have achieved good results but may not be feasible or appropriate in many resource-limited settings. Médecins sans Frontières has treated HIV in vertical programs since 2000 and over time integrated HIV treatment into general health care services using simplified protocols. We analyzed the survival probability among patients receiving antiretroviral therapy (ART) from 2003 to 2010 in integrated versus vertical programs in 9 countries in sub-Saharan Africa.
    • Simplifying and adapting antiretroviral treatment in resource-poor settings: a necessary step to scaling-up.

      Calmy, A; Klement, E; Teck, R; Berman, D; Pécoul, B; Ferradini, L (Wolters Kluwer, 2004-12-03)