• Lamivudine monotherapy as a holding regimen for HIV-positive children.

      Patten, G; Bernheimer, J; Fairlie, L; Rabie, H; Sawry, S; Technau, K; Eley, B; Davies, MA (Public Library of Science, 2018-10-11)
      BACKGROUND: In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes. METHODS: We describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART. FINDINGS: We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3-14.6), duration on cART was 3.6 years (IQR 2.0-5.9) and median CD4 count was 605.5 cells/μL (IQR 427-901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7-55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3-73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART. INTERPRETATION: Most patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.
    • (The Lancet)red: a missed opportunity.

      Calmy, A; Pascual, F; Shettle, S; de la Vega, F G; Ford, N (Elsevier, 2006-09-23)
    • The Last and First Frontier--Emerging Challenges for HIV Treatment and Prevention in the First week of Life With Emphasis on Premature and Low Birth Weight Infants

      Cotton, MF; Holgate, S; Nelson, A; Rabie, H; Wedderburn, C; Mirochnick, M (International AIDS Society, 2015-12-02)
      There is new emphasis on identifying and treating HIV in the first days of life and also an appreciation that low birth weight (LBW) and preterm delivery (PTD) frequently accompany HIV-related pregnancy. Even in the absence of HIV, PTD and LBW contribute substantially to neonatal and infant mortality. HIV-exposed and -infected infants with these characteristics have received little attention thus far. As HIV programs expand to meet the 90-90-90 target for ending the HIV pandemic, attention should focus on newborn infants, including those delivered preterm or of LBW.
    • Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique.

      Decroo, T; Panunzi, I; das Dores, C; Maldonado, F; Biot, M; Ford, N; Chu, K; South African Medical Unit, Médecins Sans Frontières, Johannesburg, South Africa. kathyrn.chu@joburg.msf.org. (2009-05-06)
      ABSTRACT: As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care.In Tete City, Mozambique, patients on antiretrovirals were rapidly down referred from a provincial hospital to four urban clinics in large numbers without careful planning, resulting in a number of patients being lost to follow-up.We outline some key lessons learned to support down referral, including the need to improve process management, clinic infrastructure, monitoring systems, and patient preparation. Down referral can be avoided by initiating patients' antiretroviral treatment at clinic level from the outset.
    • Lessons learned: Retrospective assessment of outcomes and management of patients with advanced HIV disease in a semi-urban polyclinic in Epworth, Zimbabwe.

      Blankley, S; Gashu, T; Ahmad, B; Belaye, AK; Ringtho, L; Mesic, A; Zizhou, S; Casas, EC (Public Library of Science, 2019-04-10)
      HIV continues to be one of the leading causes of infectious death worldwide and presentation with advanced HIV disease is associated with increased morbidity and mortality. Recommendations for the management of advanced HIV disease include prompt screening and treatment of opportunistic infections, rapid initiation of ART and intensified adherence support. We present treatment outcomes of a cohort of patients presenting with advanced HIV disease in a semi-urban Zimbabwean polyclinic. Retrospective cohort analysis of adult patients enrolled for care at Epworth polyclinic, Zimbabwe between 2007 and end June 2016. Treatment outcomes at 6 and 12 months were recorded. Multivariate logistical regression analysis was undertaken to identify risk factors for presentation with advanced HIV Disease (CD4 count less than 200 cells/mm3 or WHO stage 3 or 4) and risks for attrition at 12 months. 16,007 anti-retroviral therapy naive adult patients were included in the final analysis, 47.4% of whom presented with advanced HIV disease. Patients presenting with advanced HIV disease had a higher mortality rate at 12 months following enrollment compared to early stage patients (5.11% vs 0.45%). Introduction of a package of differentiated care for patients with a CD4 count of less than 100 cells/mm3 resulted in diagnosis of cryptococcal antigenaemia in 7% of patients and a significant increase in the diagnosis of TB, although there was no significant difference in attrition at 6 or 12 months for these patients compared to those enrolled prior to the introduction of the differentiated care. The burden of advanced HIV disease remained high over the study period in this semi-urban polyclinic in Zimbabwe. Introduction of a package of differentiated care for those with advanced HIV disease increased the diagnosis of opportunistic infections and represents a model of care which can be replicated in other polyclinics in the resource constrained Zimbabwean context.
    • Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies

      Johnson, Leigh F; Mossong, Joel; Dorrington, Rob E; Schomaker, Michael; Hoffmann, Christopher J; Keiser, Olivia; Fox, Matthew P; Wood, Robin; Prozesky, Hans; Giddy, Janet; et al. (Public Library of Science, 2013-04-09)
      Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.
    • Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda

      Mills, Edward J; Bakanda, Celestin; Birungi, Josephine; Chan, Keith; Ford, Nathan; Cooper, Curtis L; Nachega, Jean B; Dybul, Mark; Hogg, Robert S; University of Ottawa, Ottawa, Ontario, Canada; The AIDS Support Organization, Kampala, Uganda; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada; Medecins Sans Frontieres, Geneva, Switzerland; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town and Stellenbosch University, Cape Town, South Africa; The Ottawa Hospital, Ottawa, Ontario, Canada; Simon Fraser University, Burnaby, British Columbia, Canada; O’Neill Institute for National and Global Health Law, Georgetown University, Washington, DC (American College of Physicians, 2011-07-18)
      Little is known about the effect of combination antiretroviral therapy (cART) on life expectancy in sub-Saharan Africa.
    • Life in the Time of Antiretrovirals in South Africa

      Furin, J; Isaakidis, P (Elsevier, 2016-12-09)
    • Lived experiences of palliative care among people living with HIV/AIDS: a qualitative study from Bihar, India.

      Nair, M; Kumar, P; Mahajan, R; Harshana, A; Richardson, K; Moreto-Planas, L; Burza, S (BMJ Publishing Group, 2020-10-05)
      Objectives: This study aimed to assess the lived experiences of palliative care among critically unwell people living with HIV/AIDS (PLHA), caregivers and relatives of deceased patients. It also aimed to understand the broader palliative care context in Bihar. Design: This was an exploratory, qualitative study which used thematic analysis of semistructured, in-depth interviews as well as a focus group discussion. Setting: All interviews took place in a secondary care hospital in Patna, Bihar which provides holistic care to critically unwell PLHA. Participants: We purposively selected 29 participants: 10 critically unwell PLHA, 5 caregivers of hospitalised patients, 7 relatives of deceased patients who were treated in the secondary care hospital and 7 key informants from community-based organisations. Results: Critically ill PLHA emphasised the need for psychosocial counselling and opportunities for social interaction in the ward, as well as a preference for components of home-based palliative care, even though they were unfamiliar with actual terms such as 'palliative care' and 'end-of-life care'. Critically unwell PLHA generally expressed preference for separate, private inpatient areas for end-of-life care. Relatives of deceased patients stated that witnessing patients' deaths caused trauma for other PLHA. Caregivers and relatives of deceased patients felt there was inadequate time and space for grieving in the hospital. While both critically ill PLHA and relatives wished that poor prognosis be transparently disclosed to family members, many felt it should not be disclosed to the dying patients themselves. Conclusions: Despite expected high inpatient fatality rates, PLHA in Bihar lack access to palliative care services. PLHA receiving end-of-life care in hospitals should have a separate dedicated area, with adequate psychosocial counselling and activities to prevent social isolation. Healthcare providers should make concerted efforts to inquire, understand and adapt their messaging on prognosis and end-of-life care based on patients' preferences.
    • Long-term clinical, immunological and virological outcomes of patients on antiretroviral therapy in southern Myanmar

      Bermúdez-Aza, EH; Shetty, S; Ousley, J; Kyaw, NTT; Soe, TT; Soe, K; Mon, PE; Tun, KT; Ciglenecki, I; Cristofani, S; et al. (Public Library of Science, 2018-02-08)
      To study the long-term clinical, immunological and virological outcomes among people living with HIV on antiretroviral therapy (ART) in Myanmar.
    • Long-term virologic responses to antiretroviral therapy among HIV-positive patients entering adherence clubs in Khayelitsha, Cape Town, South Africa: a longitudinal analysis

      Kehoe, K; Boulle, A; Tsondai, PR; Euvrard, J; Davies, MA; Cornell, M (Wiley, 2020-05-14)
      Introduction In South Africa, an estimated 4.6 million people were accessing antiretroviral therapy (ART) in 2018. As universal Test and Treat is implemented, these numbers will continue to increase. Given the need for lifelong care for millions of individuals, differentiated service delivery models for ART services such as adherence clubs (ACs) for stable patients are required. In this study, we describe long‐term virologic outcomes of patients who have ever entered ACs in Khayelitsha, Cape Town. Methods We included adult patients enrolled in ACs in Khayelitsha between January 2011 and December 2016 with a recorded viral load (VL) before enrolment. Risk factors for an elevated VL (VL >1000 copies/mL) and confirmed virologic failure (two consecutive VLs >1000 copies/mL one year apart) were estimated using Cox proportional hazards models. VL completeness over time was assessed. Results Overall, 8058 patients were included in the analysis, contributing 16,047 person‐years of follow‐up from AC entry (median follow‐up time 1.7 years, interquartile range [IQR]:0.9 to 2.9). At AC entry, 74% were female, 46% were aged between 35 and 44 years, and the median duration on ART was 4.8 years (IQR: 3.0 to 7.2). Among patients virologically suppressed at AC entry (n = 8058), 7136 (89%) had a subsequent VL test, of which 441 (6%) experienced an elevated VL (median time from AC entry 363 days, IQR: 170 to 728). Older age (adjusted hazard ratio [aHR] 0.64, 95% confidence interval [CI] 0.46 to 0.88), more recent year of AC entry (aHR 0.76, 95% CI 0.68 to 0.84) and higher CD4 count (aHR 0.67, 95% CI 0.54 to 0.84) were protective against experiencing an elevated VL. Among patients with an elevated VL, 52% (150/291) with a repeat VL test subsequently experienced confirmed virologic failure in a median time of 112 days (IQR: 56 to 168). Frequency of VL testing was constant over time (82 to 85%), with over 90% of patients remaining virologically suppressed. Conclusions This study demonstrates low prevalence of elevated VLs and confirmed virologic failure among patients who entered ACs. Although ACs were expanded rapidly, most patients were well monitored and remained stable, supporting the continued rollout of this model.
    • 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.
    • Loss to follow up from isoniazid preventive therapy among adults attending HIV voluntary counseling and testing sites in Uganda.

      Namuwenge, P M; Mukonzo, J K; Kiwanuka, N; Wanyenze, R; Byaruhanga, R; Bissell, K; Zachariah, R; Makerere University School of Public Health P.O. Box 7072 Kampala Uganda; AIDS Information Centre headquarters, P.O. Box 10446 Kampala, Uganda. (2012-02)
      Among HIV-infected adults attending non-governmental organization voluntary counseling and testing (VCT) sites in Uganda that provide a nine-month course of isoniazid preventive treatment (IPT), we report on loss to follow-up (LTFU) and its associated risk factors. The design was a retrospective cohort study of program data spanning a three year period (2006-2008). A total of 586 IPT patients were enrolled of whom 335 (57.1%) were females with a mean age of 34 years. Of those starting IPT, 341 (58.1%) were lost to follow-up, 197 (33.6%) completed IPT, 29 (4.9%) were discontinued and 19 (3.2%) died. The return rates at one, three, five and seven months were 78.0% (457), 62.1% (364), 52.9% (310) and 33.6% (197) respectively. Being less than 30 years of age, widowed, separated, or divorced were found to be associated with a higher risk of loss to follow-up. Sudden improvement in retention on IPT was observed between the years 2006 and 2007, although causes of the improvement are poorly understood hence the need for more research. At non-governmental VCT sites in Uganda, six out of ten individuals enrolled on IPT are lost to follow-up and efforts to reduce this attrition including systems strengthening might play a critical role in the success of IPT programs.
    • Low Incidence of Renal Dysfunction Among HIV-Infected Patients on a Tenofovir-Based First Line Antiretroviral Treatment Regimen in Myanmar

      Kyaw, Nang Thu Thu; Harries, Anthony D; Chinnakali, Palanivel; Antierens, Annick; Soe, Kyi Pyar; Woodman, Mike; Das, Mrinalini; Shetty, Sharmila; Zuu, Moe Khine Lwin; Htwe, Pyae Sone; et al. (Public Library of Science, 2015)
      Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction.
    • 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.
    • Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

      Murphy, R A; Sunpath, H; Taha, B; Kappagoda, S; Maphasa, K T M; Kuritzkes, D R; Smeaton, L; Doctors Without Borders USA, New York, USA; McCord Hospital, South Africa; Harvard Medical School, Massachusetts, USA; Division of Infectious Disease and Geographic Medicine, California, USA; Zoe-Life, South Africa; Section of Retroviral Therapeutics, Massachusetts, USA; Centre for Biostatistics in AIDS Research, Massachusetts, USA (2010-07-01)
      A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival.
    • Malawi's contribution to "3 by 5": achievements and challenges

      Libamba, Edwin; Makombe, Simon D; Harries, Anthony D; Schouten, Erik J; Yu, Joseph Kwong-Leung; Pasulani, Olesi; Mhango, Eustice; Aberle-Grasse, John; Hochgesang, Mindy; Limbambala, Eddie; et al. (2007-02-01)
      PROBLEM: Many resource-poor countries have started scaling up antiretroviral therapy (ART). While reports from individual clinics point to successful implementation, there is limited information about progress in government institutions at a national level. APPROACH: Malawi started national ART scale-up in 2004 using a structured approach. There is a focus on one generic, fixed-dose combination treatment with stavudine, lamivudine and nevirapine. Treatment is delivered free of charge to eligible patients with HIV and there is a standardized system for recruiting patients, monthly follow-up, registration, monitoring and reporting of cases and outcomes. All treatment sites receive quarterly supervision and evaluation. LOCAL SETTING: In January 2004, there were nine public sector facilities delivering ART to an estimated 4 000 patients. By December 2005, there were 60 public sector facilities providing free ART to 37,840 patients using national standardized systems. Analysis of quarterly cohort treatment outcomes at 12 months showed 80% of patients were alive, 10% dead, 9% lost to follow-up and 1% had stopped treatment. LESSONS LEARNED: Achievements were the result of clear national ART guidelines, implementing partners working together, an intensive training schedule focused on clinical officers and nurses, a structured system of accrediting facilities for ART delivery, quarterly supervision and monitoring, and no stock-outs of antiretroviral drugs. The main challenges are to increase the numbers of children, pregnant women and patients with tuberculosis being started on ART, and to avert high early mortality and losses to follow-up. The capacity of the health sector to cope with escalating case loads and to scale up prevention alongside treatment will determine the future success of ART delivery in Malawi.
    • Management of BU-HIV co-infection

      O'Brien, D P; Ford, N; Vitoria, M; Christinet, V; Comte, E; Calmy, A; Stienstra, Y; Eholie, S; Asiedu, K (2014-06-20)
      Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking.
    • [Management of HIV/AIDS patients in Kompong Cham, Cambodia]

      Allemand-Sourrieu, J; Gazin, P; Moreau, J; Programme MSF-France de traitement du sida au Cambodge. allemandjulie@yahoo.fr (2007-02)
      In 2003 the NGO Médecins sans Frontières started an anti-viral drug treatment program for HIV/AIDS patients in the regional hospital of Kompong Cham, Cambodia. In 2005 a total of 1100 adults and 149 children were on the active list. Sixty percent of new patients were at WHO stages 3 or 4. Compliance with HAART was high after 24 months. Access to second-line regimens is discussed.