• Viewpoint: Why do we need a point-of-care CD4 test for low-income countries?

      Zachariah, R; Reid, S D; Chaillet, P; Massaquoi, M; Schouten, E J; Harries, A D; Médecins sans Frontières, Operational Centre Brussels; CD4 Initiative, Institute for Global Health, UK; Clinton Health Access Initiative, Liberia; Department of HIV/AIDS, Ministry of Health, Malawi; Management Sciences for Health, Malawi; International Union against Tuberculosis and Lung Disease, France; London School of Hygiene and Tropical Medicine, UK (2010-11-02)
      In this paper, we discuss the reasons why we urgently need a point-of-care (POC) CD4 test, elaborate the problems we have experienced with the current technology which hampers CD4-count coverage and highlight the ideal characteristics of a universal CD4 POC test. It is high-time that CD4 technology is simplified and adapted for wider use in low-income countries to change the current paradigm of restricted access once and for all.
    • Village-based AIDS prevention in a rural district in Uganda.

      Schopper, D; Doussantousse, S; Ayiga, N; Ezatirale, G; Idro, W J; Homsy, J; Médecins Sans Frontières, Geneva, Switzerland. (Oxford Journals, 1995-06)
      OBJECTIVE: To design, implement and evaluate a village-based AIDS prevention programme in a rural district in north-western Uganda. A baseline KAP survey of the general population was carried out to design a district-wide information campaign and condom promotion programme. Eighteen months later the impact achieved was measured through a second KAP survey, using the same methodology. METHODS: Anonymous structured interviews were conducted in March 1991 and October 1992 with 1486 and 1744 randomly selected individuals age 15-49, respectively. RESULTS: At 18 months, 60% of respondents had participated in an information session in the past year (47% women, 71% men) and 42% had received a pamphlet about AIDS (26% women, 58% men). Knowledge about AIDS, high initially (94%), reached 98%. More respondents knew that the incubation period is longer than one year (from 29% to 40%), and were willing to take care of a PWA (from 60% to 77%). Knowledge about condoms increased from 26 to 63% in women and 57 to 91% in men. Ever use of condoms among persons having engaged in casual sex in the past year increased from 6 to 33% in women, and 27 to 48% in men. Fifty per cent of condom users criticized lack of regular access to condoms. CONCLUSIONS: This is the first documented example of the impact a village-based AIDS prevention programme can achieve in a rural African community. Critical areas to be improved were identified, such as: women must be given better access to information, more attention must be paid to explain the asymptomatic state of HIV infection in appropriate terms, and condom social marketing must be developed.
    • Viraemia and HIV-1 drug resistance mutations among patients receiving antiretroviral treatment in Mozambique.

      Maldonado, F; Biot, M; Roman, F; Masquelier, C; Anapenge, M; Bastos, R; Chuquela, H C; Arendt, V; Schmit, J; Zachariah, R; et al. (2008-09-17)
      This study was conducted among individuals taking first-line antiretroviral treatment (ART) for at least 12 months under programme conditions in Maputo, Mozambique in order to report on the level of detectable viraemia and the proportion and types of drug resistance mutations among those with detectable viral loads. HIV-1 RNA viral load levels (lower detection limit <50 copies/ml) were measured, and resistance mutations were sequenced. One hundred and forty-nine consecutive patients (69% females, median age 36 years) were included after a mean follow-up time of 23 months. One hundred and seven (72%; 95% CI 64-79) had undetectable viral load, while in 42 (28%, 95% CI 21-36) viral load was detectable (range 50-58884 copies/ml). From 15 patients with viral load >1000 copies/ml, 12 viruses were sequenced: eight were C subtypes and four were circulating recombinant forms (CRF08). Eight (5%; 95% CI 2-9) patients with detectable viral load had one or more major resistance mutations. Nucleoside reverse transcriptase inhibitor (NRTI) and non-NRTI mutations were observed. There were no major mutations for resistance to protease inhibitors. In Maputo, the level of detectable viraemia is reassuringly low. While embarking on ART scale-up, wider surveillance is warranted to monitor programme quality and limit the development of drug resistance, which remains a major potential challenge for the future of ART in Africa.
    • Viral load for HIV treatment failure management: a report of eight drug-resistant tuberculosis cases co-infected with HIV requiring second-line antiretroviral treatment in Mumbai, India

      Andries, Aristomo; Das, Mrinalini; Isaakidis, Petros; Saranchuk, Peter (American Society of Tropical Medicine and Hygiene, 2013-12)
    • Viral Load Monitoring as a Tool to Reinforce Adherence: A Systematic Review

      Bonner, Kimberly; Mezochow, Alyssa; Roberts, Teri; Ford, Nathan; Cohn, Jennifer; Access Campaign, Médecins Sans Frontières, Geneva, Switzerland. Kimberly.bonner@geneva.msf.org (Lippincott Williams & Wilkins, 2013-09-01)
      Viral load monitoring has been proposed as a tool to reinforce adherence, but outcomes have never been systematically assessed.
    • Viral load monitoring in resource-limited settings: a medical and public health priority.

      Ford, Nathan; Roberts, Teri; Calmy, Alexandra; Medecins Sans Frontieres, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town; HIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, Geneva, Switzerland. (2012-08-24)
    • Viral Load Monitoring of Antiretroviral Therapy, cohort viral load and HIV transmission in Southern Africa: A Mathematical Modelling Analysis

      Estill, Janne; Aubrière, Cindy; Egger, Matthias; Johnson, Leigh; Wood, Robin; Garone, Daniela; Gsponer, Thomas; Wandeler, Gilles; Boulle, Andrew; Davies, Mary-Ann; et al. (2012-03-20)
      In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.
    • Viral load testing in a resource-limited setting: quality control is critical.

      Greig, Jane; du Cros, Philipp; Klarkowski, Derryck; Mills, Clair; Jørgensen, Steffen; Harrigan, P Richard; O'Brien, Daniel P; Manson Unit, Médecins Sans Frontières, London, UK. jane.greig@london.msf.org. (2011-05)
      ABSTRACT:
    • Viral Load Versus CD4⁺ Monitoring and 5-Year Outcomes of Antiretroviral Therapy in HIV-Positive Children in Southern Africa: a Cohort-Based Modelling Study

      Salazar-Vizcaya, L; Keiser, O; Karl, T; Davies, MA; Haas, Andreas D; Blaser, N; Cox, V; Eley, B; Rabie, H; Moultrie, H; et al. (Lippincott Williams & Wilkins, 2014-10-23)
      Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring.
    • Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen.

      Keene, CM; Griesel, R; Zhao, Y; Gewabe, Z; Sayed, K; Hill, A; Cassidy, T; Ngwenya, O; Jackson, A; van Zyl, G; et al. (Gower Academic Journals, 2021-07-15)
      Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design: Single arm, prospective, interventional study. Setting: Two primary care clinics in Khayelitsha, South Africa. Participants: Sixty adult patients with two viral loads greater than 1000 copies/ml. Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction. Primary outcome: Proportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4+ cell count was 248 cells/μl, viral load 10 580 copies/ml and 48 of 54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51 of 60 [85%, 95% confidence interval (CI) 73-93%] were virologically suppressed, six had viral load 50-100 copies/ml, one had viral load 100-1000 copies/ml, one no viral load in window, and one switched because of tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29 of 35 (83%, 95% CI 66-93%) with resistance to tenofovir and XTC, 11 of 13 (85%, 95% CI 55-98%) with resistance to XTC, and six of six (100%, 95% CI 54-100%) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/ml). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.
    • Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

      Davies, Mary-Ann; Moultrie, Harry; Eley, Brian; Rabie, Helena; Van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Technau, Karl; Keiser, Olivia; Egger, Matthias; et al. (Lippincott Williams & Wilkins, 2011-03-01)
      With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.
    • Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

      Nyakato, P; Schomaker, M; Sipambo, N; Technau, KG; Fatti, G; Rabie, H; Tanser, F; Eley, B; Euvrard, J; Wood, R; et al. (Lippincott, Williams & Wilkins, 2021-01-21)
      Background and objectives: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with nonperinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. Design: A retrospective cohort study Methods: We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. Results: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a nonnucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. Conclusions: As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
    • Vital status of pre-ART and ART patients defaulting from care in rural Malawi

      McGuire, Megan; Munyenyembe, Tamika; Szumilin, Elisabeth; Heinzelmann, Annette; Le Paih, Mickael; Bouithy, Nenette; Pujades-Rodríguez, Mar; Médecins Sans Frontières, Chiradzulu, Malawi; Médecins Sans Frontières, Paris, France; Epicentre, Paris, France (2010-04-29)
      OBJECTIVES: To ascertain the outcome of pre-Antiretroviral therapy (ART) and ART patients defaulting from care and investigate reasons for defaulting. METHODS: Patients defaulting from HIV care in Chiradzulu between July 2004 and September 2007 were traced at last known home address. Deaths and moves were recorded, and patients found alive were interviewed. Defaulting was defined as missed last appointment by more than 1 month among patients of unknown vital status. RESULTS: A total of 1637 individuals were traced (54%-88% of eligible), 981 pre-ART and 656 ART patients. Of 694 pre-ART patients found, 49% had died (51% of adults and 38% of children), a median of 47 days after defaulting, and 14% had moved away. Of 451 ART patients found, 54% had died (54% of adults and 50% of children), a median of 52 days after defaulting, and 20% had moved away. Overall, 221 patients were interviewed (90% of those found alive), 42% had worked outside the district in the previous year; 49% of pre-ART and 19% of ART patients had not disclosed their HIV status to other household members. Main reasons for defaulting were stigma (43%), care dissatisfaction (34%), improved health (28%) and for ART discontinuation, poor understanding of disease or treatment (56%) and drug side effects (42%). CONCLUSION: This study in a rural African HIV programme reveals the dynamics related to health service access and use, and it provides information to correct programme mortality estimates for adults and children.
    • Voluntary Community Human Immunodeficiency Virus Testing, Linkage, and Retention in Care Interventions in Kenya: Modeling the Clinical Impact and Cost-effectiveness

      Luong Nguyen, LB; Yazdanpanah, Y; Maman, D; Wanjala, S; Vandenbulcke, A; Price, J; Parker, RA; Hennequin, W; Mendiharat, P; Freedberg, KA (Oxford University Press, 2018-05-08)
      In southwest Kenya, the prevalence of human immunodeficiency virus (HIV) infection is about 25%. Médecins Sans Frontières has implemented a voluntary community testing (VCT) program, with linkage to care and retention interventions, to achieve the Joint United Nations Program on HIV and AIDS (UNAIDS) 90-90-90 targets by 2017. We assessed the effectiveness and cost-effectiveness of these interventions.
    • Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

      Zachariah, R; Spielmann M P; Chinji, C; Gomani, P; Arendt, V; Hargreaves, N J; Salaniponi, F M L; Harries, A D; Medecins Sans Frontieres-Luxembourg, Blantyre, Malawi. zachariah@internet.Lu (2003-05-02)
      OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions.
    • "We Are Part of a Family". Benefits and Limitations of Community ART Groups (CAGs) in Thyolo, Malawi: a Qualitative Study

      Pellecchia, U; Baert, S; Nundwe, S; Bwanali, A; Zamadenga, B; Metcalf, CA; Bygrave, H; Daho, S; Ohler, L; Chibwandira, B; et al. (International AIDS Society, 2017-03-28)
      In 2012 Community ART Groups (CAGs), a community-based model of antiretroviral therapy (ART) delivery were piloted in Thyolo District, Malawi as a way to overcome patient barriers to accessing treatment, and to decrease healthcare workers' workload. CAGs are self-formed groups of patients on ART taking turns to collect ART refills for all group members from the health facility. We conducted a qualitative study to assess the benefits and challenges of CAGs from patients' and healthcare workers' (HCWs) perspectives.
    • "We give them threatening advice…": expectations of adherence to antiretroviral therapy and their consequences among adolescents living with HIV in rural Malawi

      Burns, R; Magalasi, D; Blasco, P; Szumilin, E; Pasquier, E; Schramm, B; Wringe, A (Wiley, 2020-03-02)
      Introduction Many adolescents living with HIV in sub‐Saharan Africa struggle to achieve optimal adherence to antiretroviral therapy (ART), but few studies have investigated how their treatment‐taking decisions are influenced by their social interactions with providers, caregivers and community leaders. This study aims to explore the narratives that define expectations of adherence to ART among adolescents living with HIV in a rural Malawian setting. Methods Overall, 45 in‐depth interviews were conducted in 2016 with adolescents living with HIV, caregivers, health workers and community leaders, and four group sessions using participatory tools were undertaken with adolescents. Interviews and group sessions were audio‐recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. Results Adolescents were given strict behavioural codes around optimal treatment adherence, which were often enforced through encouragement, persuasian and threats. In HIV clinics, some staff supported adolescents with broader concerns relating to living with HIV, but other measures to address sub‐optimal adherence in HIV clinics were perceived by patients as punitive, including pill‐counts and increased frequency of clinic visits. Community leaders felt responsible for young peoples' health, sometimes attempting to influence their treatment‐taking by threatening to withdraw services, or to publically “out” those deemed to be non‐adherent. At home, discussions with adolescents about HIV were often limited to dose reminders, and some caretakers resorted to physical punishment to ensure adherence. While some adolescents complied with strictly‐enforced adherence rules, others demonstrated resistance by hiding missed doses, secretly throwing away drugs, or openly refusing to take them. Conclusions The potential of young people to adhere to their ART may be undermined by restrictive messages and punitive approaches to enforce and control their engagement with treatment at home, in the clinic and in the wider community. Interventions should focus on creating safe spaces for adolescents to speak frankly about the adherence challenges that they face and support for caregivers including home‐based interventions.
    • Weight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir.

      van Griensven, J; Zachariah, R; Rasschaert, F; Atté, E F; Reid, T; Médecins Sans Frontières, 7089 Kigali, Rwanda. (2009-02-01)
      This cohort study was conducted amongst female patients manifesting lipoatrophy while receiving stavudine-containing first-line antiretroviral treatment regimens at two urban health centres in Rwanda. The objectives were to assess weight evolution after stavudine substitution and to describe any significant difference in weight evolution when zidovudine or tenofovir/abacavir was used for substitution. All adult patients on stavudine-containing first-line regimens who developed lipoatrophy (diagnosed using a lipodystrophy case definition study-based questionnaire) and whose treatment regimen was changed were included (n=114). In the most severe cases stavudine was replaced with tenofovir or abacavir (n=39), and in the remainder with zidovudine (n=75). For patients changed to zidovudine a progressive weight loss was seen, while those on tenofovir/abacavir showed a progressive weight increase from six months. The between-group difference in weight evolution was significant from nine months (difference at 12 months: 2.3kg, P=0.02). These differences were confirmed by follow-up lipoatrophy scores. In multivariate analysis, substitution with tenofovir/abacavir remained significantly associated with weight gain. This is the first study in Africa assessing weight gain as a proxy for recovery after stavudine substitution due to lipoatrophy, providing supporting evidence that tenofovir/abacavir is superior to zidovudine. The weight loss with zidovudine might justify earlier substitution and access to better alternatives like tenofovir/abacavir.
    • Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries

      Madec, Yoann; Szumilin, Elisabeth; Genevier, Christine; Ferradini, Laurent; Balkan, Suna; Pujades, Mar; Fontanet, Arnaud; Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Medecins Sans Frontieres, Paris, France; Medecins Sans Frontieres, Nairobi, Kenya; Infectious Diseases Department, Khmero-Soviet Friendship Hospital, Phnom Penh, Cambodia; Epicentre, Paris, France (2009-04-27)
      BACKGROUND: In developing countries, access to laboratory tests remains limited, and the use of simple tools such as weight to monitor HIV-infected patients treated with antiretroviral therapy should be evaluated. METHODS: Cohort study of 2451 Cambodian and 2618 Kenyan adults who initiated antiretroviral therapy between 2001 and 2007. The prognostic value of weight gain at 3 months of antiretroviral therapy on 3-6 months mortality, and at 6 months on 6-12 months mortality, was investigated using Poisson regression. RESULTS: Mortality rates [95% confidence interval (CI)] between 3 and 6 months of antiretroviral therapy were 9.9 (7.6-12.7) and 13.5 (11.0-16.7) per 100 person-years in Cambodia and Kenya, respectively. At 3 months, among patients with initial body mass index less than or equal to 18.5 kg/m (43% of the study population), mortality rate ratios (95% CI) were 6.3 (3.0-13.1) and 3.4 (1.4-8.3) for those with weight gain less than or equal to 5 and 5-10%, respectively, compared with those with weight gain of more than 10%. At 6 months, weight gain was also predictive of subsequent mortality: mortality rate ratio (95% CI) was 7.3 (4.0-13.3) for those with weight gain less than or equal to 5% compared with those with weight gain of more than 10%. CONCLUSION: Weight gain at 3 months is strongly associated with survival. Poor compliance or undiagnosed opportunistic infections should be investigated in patients with initial body mass index less than or equal to 18.5 and achieving weight gain less than or equal to 10%.
    • Weight loss after the first year of stavudine-containing antiretroviral therapy and its association with lipoatrophy, virological failure, adherence and CD4 counts at primary health care level in Kigali, Rwanda.

      van Griensven, Johan; Zachariah, Rony; Mugabo, Jules; Reid, Tony; Médecins Sans Frontières, Operational Centre Brussels, Medical Department, Duprestraat 94, 1090 Brussels, Belgium. jvgrie@yahoo.com (2010-12)
      This study was conducted among 609 adults on stavudine-based antiretroviral treatment (ART) for at least one year at health center level in Kigali, Rwanda to (a) determine the proportion who manifest weight loss after one year of ART (b) examine the association between such weight loss and a number of variables, namely: lipoatrophy, virological failure, adherence and on-treatment CD4 count and (c) assess the validity and predictive values of weight loss to identify patients with lipoatrophy. Weight loss after the first year of ART was seen in 62% of all patients (median weight loss 3.1 kg/year). In multivariate analysis, weight loss was significantly associated with treatment-limiting lipoatrophy (adjusted effect/kg/year -2.0 kg, 95% confidence interval -0.6;-3.4 kg; P<0.01). No significant association was found with virological failure or adherence. Higher on-treatment CD4 cell counts were protective against weight loss. Weight loss that was persistent, progressive and/or chronic was predictive of lipoatrophy, with a sensitivity and specificity of 72% and 77%, and positive and negative predictive values of 30% and 95%. In low-income countries, measuring weight is a routine clinical procedure that could be used to filter out individuals with lipoatrophy on stavudine-based ART, after alternative causes of weight loss have been ruled out.