• 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.
    • Clinical screening for HIV in a health centre setting in urban Kenya: an entry point for voluntary counselling, HIV testing and early diagnosis of HIV infection?

      Arendt, V; Mossong, J; Zachariah, R; Inwani, C; Farah, B; Robert, I; Waelbrouck, A; Fonck, K; Médecins Sans Frontières, Mission Kenya, Brussels Operational Centre, Brussels, Belgium. (2007-01)
      A study was conducted among patients attending a public health centre in Nairobi, Kenya in order to (a) verify the prevalence of HIV, (b) identify clinical risk factors associated with HIV and (c) determine clinical markers for clinical screening of HIV infection at the health centre level. Of 304 individuals involved in the study,107(35%) were HIV positive. A clinical screening algorithm based on four clinical markers, namely oral thrush, past or present TB, past or present herpes zoster and prurigo would pick out 61 (57%) of the 107 HIV-positive individuals. In a resource-poor setting, introducing a clinical screening algorithm for HIV at the health centre level could provide an opportunity for targeting voluntary counselling and HIV testing, and early access to a range of prevention and care interventions.
    • Conceptions of Agency and Constraint for HIV-Positive Patients and Healthcare Workers to Support Long-Term Engagement With Antiretroviral Therapy Care in Khayelitsha, South Africa

      Stern, E; Colvin, C; Gxabagxaba, N; Schutz, C; Burton, R; Meintjes, G (Taylor & Francis, 2017-03-01)
      In the context of the optimism around antiretroviral therapy (ART) as prevention of HIV/AIDS, addressing the barriers to long-term ART adherence is critical. This is particularly important given the tendency to individualise or use a blame discourse when exploring why HIV-infected patients "fail" to adequately adhere to ART, and not sufficiently exploring contextual reasons for poor adherence that may require varying solutions. This study took place at three clinics and one hospital in Khayelitsha, South Africa, to document the contextual factors that challenged ART adherence in this community. Interviews were conducted with 20 HIV-infected patients who had defaulted on their ART and were subsequently admitted to Khayelitsha hospital for clinical complications, and 9 ART service providers including doctors, nurses and HIV counsellors. Interviews assessed the reasons patients defaulted on ART and explored ways this could be prevented. Data from both groups were analysed collectively using thematic analysis. While the interviews revealed a landscape of environmental risks threatening adherence to ART, all patients managed to overcome the identified barriers at some point in their treatment phase, indicating the fluidity of patients' needs and decision making. Patients reported that distrustful relationships with service providers could inhibit their understanding of ART and/or interrupt their follow-up at clinics. Patients described their rationale and agency underlying non-adherence, such as testing their bodies' physical limits without ART medication. The study speaks to the need to appreciate contextual social and structural barriers related to ART adherence, and how these are negotiated differently by specific sub-groups, to support an appropriate response. It is imperative to not solely emphasise loss to follow-up but also assess patients' subjective trajectory of their ART journey, decision making and agency with adhering to ART, their relations with healthcare workers, and how these dynamics are intertwined with broader constraints in health systems.
    • Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

      Fenner, Lukas; Brinkhof, Martin W G; Keiser, Olivia; Weigel, Ralf; Cornell, Morna; Moultrie, Harry; Prozesky, Hans; Technau, Karl; Eley, Brian; Vaz, Paula; Pascoe, Margaret; Giddy, Janet; Van Cutsem, Gilles; Wood, Robin; Egger, Matthias; Davies, Mary-Ann; Institute of Social and Preventive Medicine, University of Bern, Switzerland. lfenner@ispm.unibe.ch (2010-08-15)
      BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.
    • HIV Prevalence and Demographic Risk Factors in Blood Donors.

      Zachariah, R; Harries, A D; Nkhoma, W; Arendt, V; Spielmann M P; Buhendwa, L; Chingi, C; Mossong, J; Medecins Sans Frontieres, Luxembourg, Blantyre, Malawi. (2002-02)
      OBJECTIVES: To estimate HIV prevalence in various blood donor populations, to identity sociodemographic risk factors associated with prevalent HIV and to assess the feasibility of offering routine voluntary counselling services to blood donors. DESIGN: Cross-sectional study. SETTING: Thyolo district, Malawi. METHODS: Data analysis involving blood donors who underwent voluntary counselling and HIV testing between January 1998 and July 2000. RESULTS: Crude HIV prevalence was 22%, while the age standardised prevalence (>15 years) was 17%. Prevalence was lowest among rural donors, students and in males of the age group 15-19 years. There was a highly significant positive association of HIV prevalence with increasing urbanisation. Significant risk factors associated with prevalence for both male and female donors included having a business-related occupation, living in a semi-urban or urban area and being in the age group 25-29 years for females and 30-34 years for males. All blood donors were pre-test counselled and 90% were post test counselled in 2000. CONCLUSIONS: HIV prevalence in blood donors was alarmingly high, raising important concerns on the potential dangers of HIV transmission through blood transfusions. Limiting blood transfusions, use of a highly sensitive screening test, and pre-donation selection of donors is important. The experience also shows that it is feasible to offer pre and post test counselling services for blood donors as an entry point for early diagnosis of asymptomatic HIV infection and, broader preventive strategies including the potential of early access to drugs, for the prevention of opportunistic infections.
    • Motives, sexual behaviour, and risk factors associated with HIV in individuals seeking voluntary counselling and testing in a rural district of Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Buhendwa, L; Chingi, C; Medecins sans Frontieres, Thyolo, Malawi. zachariah@internet.lu (2003-04)
      A study was conducted among individuals seeking voluntary HIV counselling and testing (VCT) in order to (a) describe their motives and source(s) of information, (b) describe their sexual behaviour; and (c) identify risk factors associated with HIV infection. Of 723 individuals who sought VCT, the most common reason (50%) was recent knowledge of HIV/AIDS and a desire to know their HIV status. The majority (77%) underwent VCT after being encouraged by others who knew their status. Ninety five per cent reported sexual encounters, with 337 (49%) engaging in unprotected sex. HIV prevalence was 31% and an HIV-positive status was associated with being female, being over 25 years of age and/or being a farmer. There is a demand for VCT, and the service provides an opportunity for intensive education about HIV/AIDS prevention on a one-to-one basis. It could also be an entry point to prevention and care for those who are infected.
    • Population Differences in Death Rates in HIV-Positive Patients with Tuberculosis.

      Ciglenecki, I; Glynn, J R; Mwinga, A; Ngwira, B; Zumla, A; Fine, P E M; Nunn, A; Médecins Sans Frontières, Geneva, Switzerland. iza_ciglenecki@yahoo.com (International Union Against TB and Lung Disease, 2007-10)
      SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality.
    • Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

      Micol, Romain; Buchy, Philippe; Guerrier, Gilles; Duong, Veasna; Ferradini, Laurent; Dousset, Jean-Philippe; Guerin, Philippe J; Balkan, Suna; Galimand, Julie; Chanroeun, Hak; Lortholary, Olivier; Rouzioux, Christine; Fontanet, Arnaud; Leruez-Ville, Marianne; Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Laboratoire de Virologie, Universite Rene Descartes, Hopital Necker-Enfants Malades, Paris, France; Unite de virologie, Institut Pasteur du Cambodge, Phnom Penh, Cambodia; Medecins Sans Frontieres, Hopital Prea Bath Norodom Sihanouk, Phnom Penh, Cambodia; Medecins Du Monde, Hopital Kosamak, Phnom Penh, Cambodia; Epicentre, Paris, France; Medecins Sans Frontieres, Paris, France; Service des Maladies Infectieuses et Tropicales, Hopital Calmette, Phnom Penh, Cambodia; Universite Rene Descartes, Service des Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker–Pasteur, Hopital Necker–Enfants Malades, Paris, France (2009-08-01)
      BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality.
    • 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
    • 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).
    • Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort.

      Boulle, A; Orrell, C; Kaplan, R; Van Cutsem, G; McNally, M; Hilderbrand, K; Myer, L; Egger, M; Coetzee, D; Maartens, G; Wood, R; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. andrew.boulle@uct.ac.za (International Medical Press, 2007)
      INTRODUCTION: The patterns and reasons for antiretroviral therapy (ART) drug substitutions are poorly described in resource-limited settings. METHODS: Time to and reason for drug substitution were recorded in treatment-naive adults receiving ART in two primary care treatment programmes in Cape Town. The cumulative proportion of patients having therapy changed because of toxicity was described for each drug, and associations with these changes were explored in multivariate models. RESULTS: Analysis included 2,679 individuals followed for a median of 11 months. Median CD4+ T-cell count at baseline was 85 cells/microl. Mean weight was 59 kg, mean age was 32 years and 71% were women. All started non-nucleoside reverse transcriptase inhibitor-based ART (60% on efavrienz) and 75% started on stavudine (d4T). After 3 years, 75% remained in care on-site, of whom 72% remained on their initial regimen. Substitutions due to toxicity of nevirapine (8% by 3 years), efavirenz (2%) and zidovudine (8%) occurred early. Substitutions on d4T occurred in 21% of patients by 3 years, due to symptomatic hyperlactataemia (5%), lipodystrophy (9%) or peripheral neuropathy (6%), and continued to accumulate over time. Those at greatest risk of hyperlactataemia or lipodystrophy were women on ART > or =6 months, weighing > or =75 kg at baseline. DISCUSSION: A high proportion of adult patients are able to tolerate their initial ART regimen for up to 3 years. In most instances treatment-limiting toxicities occur early, but continue to accumulate over time in patients on d4T. Whilst awaiting other treatment options, the risks of known toxicities could be minimized through early identification of patients at the highest risk.
    • Targeting CD4 testing to a clinical subgroup of patients could limit unnecessary CD4 measurements, premature antiretroviral treatment and costs in Thyolo District, Malawi.

      Zachariah, R; Teck, R; Ascurra, O; Humblet, P; Harries, A D; Médecins sans Frontières, Medical Department (Operational Research HIV-TB), Brussels Operational Center, 94 Rue Dupre, Brussels, Belgium. zachariah@internet.lu (Elsevier, 2006-01)
      Malawi offers antiretroviral treatment (ART) to all HIV-positive adults who are clinically classified as being in WHO clinical stage III or IV without 'universal' CD4 testing. This study was conducted among such adults attending a rural district hospital HIV/AIDS clinic (a) to determine the proportion who have CD4 counts >or=350 cells/microl, (b) to identify risk factors associated with such CD4 counts and (c) to assess the validity and predictive values of possible clinical markers for CD4 counts >or=350 cells/microl. A CD4 count >or=350 cells/microl was found in 36 (9%) of 401 individuals who are thus at risk of being placed prematurely on ART. A body mass index (BMI) >22 kg/m(2), the absence of an active WHO indicator disease at the time of presentation for ART, and a total lymphocyte count >1,200 cells/microl were significantly associated with such a CD4 count. The first two of these variables could serve as clinical markers for selecting subgroups of patients who should undergo CD4 testing. In a resource-limited district setting, assessing the BMI and checking for active opportunistic infections are routine clinical procedures that could be used to target CD4 measurements, thereby minimising unnecessary CD4 measurements, unnecessary (too early) treatment and costs.
    • Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa.

      Fenner, Lukas; Reid, Stewart E; Fox, Matthew P; Garone, Daniela; Wellington, Maureen; Prozesky, Hans; Zwahlen, Marcel; Schomaker, Michael; Wandeler, Gilles; Kancheya, Nzali; Boulle, Andrew; Wood, Robin; Henostroza, German; Egger, Matthias; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. lfenner@ispm.unibe.ch (2013-02)
      To investigate the incidence of selected opportunistic infections (OIs) and cancers and the role of a history of tuberculosis (TB) as a risk factor for developing these conditions in HIV-infected patients starting antiretroviral treatment (ART) in Southern Africa.