• Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries.

      Greig, Jane; Casas, Esther C; O'Brien, Daniel P; Mills, Edward J; Ford, Nathan; Médecins Sans Frontières, London, UK. jane.greig@london.msf.org (2012-07-31)
      Recent studies have highlighted the increased risk of adverse outcomes among older patients on antiretroviral therapy (ART). We report on the associations between older age and adverse outcomes in HIV/AIDS antiretroviral programmes across 17 programmes in sub-Saharan Africa.
    • CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multicohort analysis from South Africa

      Hoffmann, Christopher J; Schomaker, Michael; Fox, Matthew P; Mutevedzi, Portia; Giddy, Janet; Prozesky, Hans; Wood, Robin; Garone, Daniela B; Egger, Matthias; Boulle, Andrew; et al. (Lippincott Williams & Wilkins, 2013-05-01)
      In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.
    • CD4 Testing at Clinics to Assess Eligibility for Antiretroviral Therapy

      Lumala, R; van den Akker, T; Metcalf, CA; Diggle, E; Zamadenga, B; Mbewa, K; Akkeson, A (College of Medicine, University of Malawi, 2012-06-01)
      In 2011, the Ministry of Health raised the CD4 threshold for antiretroviral therapy (ART) eligibility from <250 cells/µl and <350 cells/µl, but at the same time only 8.8% of facilities in Malawi with HIV services provided CD4 testing. We conducted a record review at 10 rural clinics in Thyolo District to assess the impact of introducing CD4 testing on identifying patients eligible for ART.
    • 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.
    • Cost and cost-effectiveness of switching from d4T or AZT to a TDF-based first-line regimen in a resource-limited setting in rural Lesotho

      Jouquet, Guillaume; Bygrave, Helen; Kranzer, Katharina; Ford, Nathan; Gadot, Laurent; Lee, Janice; Hilderbrand, Katherine; Goemaere, Eric; Vlahakis, Natalie; Trivino, Laura; et al. (Lippincott Williams & Wilkins, 2011-11-01)
      Latest World Health Organization guidelines recommend shifting away from Stavudine (d4T)-based regimens due to severe side effects. However, widespread replacement of d4T by Tenofovir (TDF) or Zidovudine (AZT) is hampered by cost concerns.
    • Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

      Singh, Ashika; Sunpath, Henry; Green, Taryn N; Padayachi, Nagavelli; Hiramen, Keshni; Lie, Yolanda; Anton, Elizabeth D; Murphy, Richard; Reeves, Jacqueline D; Kuritzkes, Daniel R; et al. (Lippincott Williams & Wilkins, 2011-11-01)
      Drug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy.
    • Evaluation of a 5-year programme to prevent mother-to-child transmission of HIV infection in Northern Uganda

      Ahoua, Laurence; Ayikoru, Harriet; Gnauck, Katherine; Odaru, Grace; Odar, Emmanuel; Ondoa-Onama, Christine; Pinoges, Loretxu; Balkan, Suna; Olson, David; Pujades-Rodríguez, Mar; et al. (2010-07-13)
      Prevention of mother-to-child transmission (PMTCT) is essential in HIV/AIDS control. We analysed 2000-05 data from mother-infant pairs in our PMTCT programme in rural Uganda, examining programme utilization and outcomes, HIV transmission rates and predictors of death or loss to follow-up (LFU). Out of 19,017 women, 1,037 (5.5%) attending antenatal care services tested HIV positive. Of these, 517 (50%) enrolled in the PMTCT programme and gave birth to 567 infants. Before tracing, 303 (53%) mother-infant pairs were LFU. Reasons for dropout were infant death and lack of understanding of importance of follow-up. Risk of death or LFU was higher among infants with no or incomplete intrapartum prophylaxis (OR = 1.90, 95% CI 1.07-3.36) and of weaning age <6 months (OR 2.55, 95% CI 1.42-4.58), and lower in infants with diagnosed acute illness (OR 0.30, 95% CI 0.16-0.55). Mother-to-child HIV cumulative transmission rate was 8.3%, and 15.5% when HIV-related deaths were considered. Improved tracking of HIV-exposed infants is needed in PMTCT programmes where access to early infant diagnosis is still limited.
    • High rates of active hepatitis B and C co-infections in HIV-1 infected Cameroonian adults initiating antiretroviral therapy

      Laurent, C; Bourgeois, A; Mpoudi-Ngolé, E; Kouanfack, C; Ciaffi, L; Nkoué, N; Mougnutou, R; Calmy, A; Koulla-Shiro, S; Ducos, J; et al. (2009-07-29)
      OBJECTIVES: To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV-infected patients initiating antiretroviral therapy in Cameroon. METHODS: Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti-hepatitis B core (anti-HBc), anti-HCV and - if HBsAg or anti-HCV result was positive or indeterminate - for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6-13.5]. The median HBV viral load was 2.47 x 10(7) IU/mL [interquartile range (IQR) 3680-1.59 x 10(8); range 270 to >2.2 x 10(8)]. Twenty-one patients (12.4%, 95% CI 7.9-18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400-2.06 x 10(6); range 640-5.5 x 10(6)). No patient was co-infected with HBV and HCV. In multivariate analysis, HCV co-infection was associated with greater age [>or=45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49-40.55, P<0.001] and abnormal serum alanine aminotransferase level [>or=1.25 x upper limit of normal (ULN) vs. <1.25 x ULN, OR 7.81, 95% CI 1.54-39.66, P=0.01]; HBV co-infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32-14.17, P=0.02). CONCLUSIONS: These high rates of active HBV and HCV co-infections in HIV-positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV-endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.
    • 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.
    • HIV prevention, care, and treatment in two prisons in Thailand.

      Wilson, D; Ford, N; Ngammee, V; Chua, A; Kyaw, M K K; Médecins Sans Frontières, Bangkapi, Bangkok, Thailand. (Public Library of Science, 2007-06)
    • 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.
    • 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.
    • 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.
    • Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate?

      Arnedo, M; Alonso, E; Eisenberg, N; Ibáñez, L; Ferreyra, C; Jaén, A; Flevaud, L; Khamadi, S; Roddy, P; Gatell, JM; et al. (Public Library of Science, 2012-12-06)
      Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate.
    • Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

      Cornell, Morna; Technau, Karl; Fairall, Lara; Wood, Robin; Moultrie, Harry; van Cutsem, Gilles; Giddy, Janet; Mohapi, Lerato; Eley, Brian; MacPhail, Patrick; et al. (2009-09)
      OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.
    • A national survey of the impact of rapid scale-up of antiretroviral therapy on health-care workers in Malawi: effects on human resources and survival.

      Makombe, S D; Jahn, A; Tweya, H; Chuka, S; Yu, J K L; Hochgesang, M; Aberle-Grasse, J; Pasulani, O; Schouten, E J; Kamoto, K; et al. (WHO, 2007-11)
      OBJECTIVE: To assess the human resources impact of Malawis rapidly growing antiretroviral therapy (ART) programme and balance this against the survival benefit of health-care workers who have accessed ART themselves. METHODS: We conducted a national cross-sectional survey of the human resource allocation in all public-sector health facilities providing ART in mid-2006. We also undertook a survival analysis of health-care workers who had accessed ART in public and private facilities by 30 June 2006, using data from the national ART monitoring and evaluation system. FINDINGS: By 30 June 2006, 59 581 patients had accessed ART from 95 public and 28 private facilities. The public sites provided ART services on 2.4 days per week on average, requiring 7% of the clinician workforce, 3% of the nursing workforce and 24% of the ward clerk workforce available at the facilities. We identified 1024 health-care workers in the national ART-patient cohort (2% of all ART patients). The probabilities for survival on ART at 6 months, 12 months and 18 months were 85%, 81% and 78%, respectively. An estimated 250 health-care workers lives were saved 12 months after ART initiation. Their combined work-time of more than 1000 staff-days per week was equivalent to the human resources required to provide ART at the national level. CONCLUSION: A large number of ART patients in Malawi are managed by a small proportion of the health-care workforce. Many health-care workers have accessed ART with good treatment outcomes. Currently, staffing required for ART balances against health-care workers lives saved through treatment, although this may change in the future.
    • Outcomes After Virologic Failure of First-Line ART in South Africa

      Murphy, Richard A; Sunpath, Henry; Lu, Zhigang; Chelin, Neville; Losina, Elena; Gordon, Michelle; Ross, Douglas; Ewusi, Aba D; Matthews, Lynn T; Kuritzkes, Daniel R; et al. (2010-04-24)
      To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART).
    • 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.
    • Preventing HIV-1: lessons from Mwanza and Rakai.

      Matthys, F; Boelaert, M (Elsevier, 1999-05-01)
    • Sustainable HIV Treatment in Africa Through Viral-Load-Informed Differentiated Care

      Phillips, A; Shroufi, A; Vojnov, L; Cohn, J; Roberts, T; Ellman, T; Bonner, K; Rousseau, C; Garnett, G; Cambiano, V; et al. (Nature Publishing Group, 2015-12-03)
      There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.