• Decreased risk of HIV-associated TB during antiretroviral therapy expansion in rural Eswatini from 2009 to 2016: a cohort and population-based analysis

      Kerschberger, B; Schomaker, M; Telnov, A; Vambe, D; Kisyeri, N; Sikhondze, W; Pasipamire, L; Ngwenya, SM; Rusch, B; Ciglenecki, I; et al. (John Wiley & Sons, 2019-07-16)
      This paper assesses patient- and population-level trends in TB notifications during rapid expansion of antiretroviral therapy in Eswatini which has an extremely high incidence of both TB and HIV. METHODS: Patient- and population-level predictors and rates of HIV-associated TB were examined in the Shiselweni region in Eswatini from 2009 to 2016. Annual population-level denominators obtained from projected census data and prevalence estimates obtained from population-based surveys were combined with individual-level TB treatment data. Patient- and population-level predictors of HIV-associated TB were assessed with multivariate logistic and multivariate negative binomial regression models. RESULTS: Of 11 328 TB cases, 71.4% were HIV co-infected and 51.8% were women. TB notifications decreased fivefold between 2009 and 2016, from 1341 to 269 cases per 100 000 person-years. The decline was sixfold in PLHIV vs. threefold in the HIV-negative population. Main patient-level predictors of HIV-associated TB were recurrent TB treatment (adjusted odds ratio [aOR] 1.40, 95% confidence interval [CI]: 1.19-1.65), negative (aOR 1.31, 1.15-1.49) and missing (aOR 1.30, 1.11-1.53) bacteriological status and diagnosis at secondary healthcare level (aOR 1.18, 1.06-1.33). Compared with 2009, the probability of TB decreased for all years from 2011 (aOR 0.69, 0.58-0.83) to 2016 (aOR 0.54, 0.43-0.69). The most pronounced population-level predictor of TB was HIV-positive status (adjusted incidence risk ratio 19.47, 14.89-25.46). CONCLUSIONS: This high HIV-TB prevalence setting experienced a rapid decline in TB notifications, most pronounced in PLHIV. Achievements in HIV-TB programming were likely contributing factors.
    • Delivering HIV Care in Challenging Operating Environments: The MSF Experience Towards Differentiated Models of Care for Settings with Multiple Basic Health Care Needs

      Ssonko, C; Gonzalez, L; Mesic, A; da Fonseca, M; Achar, J; Safar, N; Martin, B; Wong, S; Casas, E (International AIDS Society, 2017-07-21)
      Introduction: Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC). Methods: A descriptive analysis from CAR, DRC and RoSS programmes reviewing methodology and strategies of HIV care integration between 2010 and 2015 was performed. We describe HIV care models integrated within the provision of general health care and highlight best practices and challenges. Results: Services included provision of general health care, with out-patient care (range between countries 43,343 and 287,163 consultations/year in 2015) and in-patient care (range 1076–16,595 in 2015). By the end of 2015 antiretroviral therapy (ART) initiations reached 12–255 patients/year. A total of 1101 and 1053 patients were on ART in CAR and DRC, respectively. In RoSS 186 patients were on ART when conflict recommenced late in 2013. While ART initiation and monitoring were mostly clinically driven in the early phase of the programmes, DRC implemented CD4 monitoring and progressively HIV viral load (VL) monitoring during study period. Attacks to health care facilities in CAR and RoSS disrupted service provision temporarily. Programmatic challenges include: competing health priorities influencing HIV care and need to integrate within general health services. Differentiated care approaches that support continuity of care in these programmes include simplification of medical protocols, multi-month ART prescriptions, and community strategies such as ART delivery groups, contingency plans and peer support activities. Conclusions: The principles of differentiated HIV care for high-quality ART delivery can successfully be applied in challenging operating environments. However, success heavily depends on specific adaptations to each setting.
    • Demedicalizing AIDS prevention and treatment in Africa

      Ellman, Tom (Massachusetts Medical Society, 2015-01-22)
    • Demographic characteristics and opportunistic diseases associated with attrition during preparation for antiretroviral therapy in primary health centres in Kibera, Kenya.

      Tayler-Smith, K; Zachariah, R; Manzi, M; Kizito, W; Vandenbulcke, A; Dunkley, S; von Rege, D; Reid, T; Arnould, L; Suleh, A; et al. (2011-05)
      Using routine data from HIV-positive adult patients eligible for antiretroviral therapy (ART), we report on routinely collected demographic characteristics and opportunistic diseases associated with pre-ART attrition (deaths and loss to follow-up). Among 2471 ART eligible patients, enrolled between January 2005 and November 2008, 446 (18%) were lost to attrition pre-ART. Adjusted risk factors significantly associated with pre-ART attrition included age <35 years (Odds Ratio, OR 1.4, 95% Confidence Interval, CI 1.1-1.8), severe malnutrition (OR 1.5, 95% CI 1.1-2.0), active pulmonary tuberculosis (OR 1.6, 95% CI 1.1-2.4), severe bacterial infections including severe bacterial pneumonia (OR 1.9, 95% CI 1.2-2.8) and prolonged unexplained fever (>1 month), (OR 2.6, 95% CI 1.3-5.2). This study highlights a number of clinical markers associated with pre-ART attrition that could serve as 'pointers' or screening tools to identify patients who merit fast-tracking onto ART and/or closer clinical attention and follow-up.
    • Demystifying antiretrovial therapy in resource-poor settings

      Coetzee, D; Boulle, A; Kasper, T; Francoise, L; Hilderbrand, K (Essential Drugs Monitor, 2008-04-04)
    • Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

      Kaida, Angela; Matthews, Lynn T; Ashaba, Scholastic; Tsai, Alexander C; Kanters, Steve; Robak, Magdalena; Psaros, Christina; Kabakyenga, Jerome; Boum, Yap; Haberer, Jessica E; et al. (Lippincott Williams & Wilkins, 2014-12-01)
      Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown.
    • Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in sub-Saharan Africa

      Kosack, C; Shanks, L; Beelaert, G; Benson, T; Savane, A; Ng'ang'a, A; Andre, B; Zahinda, J; Fransen, K; Page, A (American Society for Microbiology, 2017-07-26)
      Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counselling sites in sub-Saharan Africa (Guinea, Conakry; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroun; Baraka, Democratic Republic of Congo). A total of 2780 samples, including 1306 HIV-positive, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDT) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of sensitivity and specificity of ≥99%. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms varied from 75.8%-100% using strategies recommended for high-prevalence settings; 98.7%-100% using strategies recommended for low-prevalence settings; and 98.1%-100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high prevalence strategy, options were often very limited due to sub-optimal performance of individual RDTs and to shared false-reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.
    • Development of dual-class antiretroviral drug resistance in a child coinfected with HIV and tuberculosis: a case report from KwaZulu-Natal, South Africa.

      Murphy, R A; France, H; Sunpath, H; Gordon, M L; Marconi, V; Kuritzkes, D R; McIntosh, K; Massachusetts General Hospital, and Brigham and Women's Hospital, Boston, MA, USA. richard.murphy@newyork.msf.org (Published by Oxford University Press, 2009-02)
      The treatment of concurrent HIV and tuberculosis (TB) in children <3 years of age has not been well-studied and is complicated by potential drug-drug interactions. The recommended antiretroviral therapy (ART) in coinfected children in South Africa consists of full-strength ritonavir, lamivudine and stavudine. We report on a child initiated on this regimen, during concurrent TB treatment, who promptly developed an adverse reaction, virologic failure and dual-class antiretroviral drug resistance, compromising subsequent salvage ART.
    • Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

      Harries, Anthony D; Zachariah, Rony; van Oosterhout, Joep J; Reid, Steven D; Hosseinipour, Mina C; Arendt, Vic; Chirwa, Zengani; Jahn, Andreas; Schouten, Erik J; Kamoto, Kelita; et al. (2010-01)
      Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings.
    • Diagnostic value of the urine lipoarabinomannan assay in HIV-positive, ambulatory patients with CD4 below 200 cells/μl in 2 low-resource settings: A prospective observational study.

      Huerga, H; Mathabire Rucker, SC; Cossa, L; Bastard, M; Amoros, I; Manhica, I; Mbendera, K; Telnov, A; Szumilin, E; Sanchez-Padilla, E; et al. (Public Library of Science, 2019-04-30)
      BACKGROUND: Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB. METHODS AND FINDINGS: We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results. CONCLUSIONS: LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.
    • Did the 2014 Ebola Outbreak in Liberia Affect HIV Testing, Linkage to Care and ART Initiation?

      Jacobs, G; Bhat, P; Owiti, P; Edwards, J; Tweya, H; Najjemba, R (International Union Against Tuberculosis and Lung Disease, 2017-06-21)
      Setting: Health facilities providing human immunodeficiency virus (HIV) testing, care and treatment in Liberia. Objective: To evaluate individuals aged ⩾15 years who were tested, diagnosed and enrolled into HIV care before (2013), during (2014) and after the Ebola outbreak (2015). Design: A cross-sectional descriptive study. Results: A median of 6930 individuals aged ⩾15 years per county were tested for HIV before the Ebola outbreak; this number declined by 35% (2444/6930) during the outbreak. HIV positivity remained similar before (7028/207 314, 3.4%) and during the outbreak (4146/121 592, 3.5%). During Ebola, HIV testing declined more in highly affected counties (68 035/127 468, 47%) than in counties that were less affected (16 444/23 955, 31%, P < 0.001). Compared to the pre-Ebola period, HIV testing in less-affected counties recovered more quickly during the post-outbreak period, with a 19% increase in testing, while medium and highly affected counties remained at respectively 38% and 48% below pre-outbreak levels. Enrolment for HIV care increased during and after the outbreak compared to the pre-Ebola period. Conclusion: HIV testing and diagnosis were significantly limited during the Ebola outbreak, with the most severe effects occurring in highly affected counties. However, enrolment for HIV care and treatment were resilient throughout the outbreak. Pro-active measures are needed to sustain HIV testing rates in future epidemics.
    • Dilution Testing Using Rapid Diagnostic Tests in a HIV Diagnostic Algorithm: a Novel Alternative for Confirmation Testing in Resource Limited Settings

      Shanks, L; Siddiqui, MR; Abebe, A; Piriou, E; Pearce, N; Ariti, C; Masiga, J; Muluneh, L; Wazome, J; Ritmeijer, K; et al. (BioMed Central, 2015-05-14)
      Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results.
    • Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

      Ford, Nathan; Nachega, Jean B; Engel, Mark E; Mills, Edward J; Médecins Sans Frontières, Cape Town, Western Cape, South Africa. (2009-11-30)
      BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None.
    • Distribution of antiretroviral treatment through self-forming groups of patients in Tete province, Mozambique

      Decroo, Tom; Telfer, Barbara; Biot, Marc; Maïkéré, Jacob; Dezembro, Sergio; Cumba, Luisa Isabel; Dores, Carla das; Chu, Kathryn; Ford, Nathan; Medecins Sans Frontieres, Tete, Mozambique; Medecins Sans Frontieres, Maputo, Mozambique; Provincial Health Department, Tete, Mozambique; Medecins Sans Frontieres, Cape Town, South Africa; Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD; and Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa (2010-11-13)
      BACKGROUND
    • Do patents prevent access to drugs for HIV in developing countries?

      Boelaert, M; Lynen, L; Van Damme, W; Colebunders, R (2002-02-20)
    • Does HIV status affect the Aetiology, Bacterial Resistance Patterns and Recommended Empiric Antibiotic Treatment in adult patients with bloodstream infection in Cambodia?

      Phe, Thong; Vlieghe, Erika; Reid, Tony; Harries, Anthony D; Lim, Kruy; Thai, Sopheak; De Smet, Birgit; Veng, Chhunheng; Kham, Chun; Ieng, Sovann; et al. (2013-01-07)
      OBJECTIVE: The microbiologic causes of bloodstream infections (BSI) may differ between HIV-positive and HIV-negative patients and direct initial empiric antibiotic treatment (i.e. treatment before culture results are available). We retrospectively assessed community-acquired BSI episodes in adults in Cambodia according to HIV status for spectrum of bacterial pathogens, antibiotic resistance patterns and appropriateness of empiric antibiotics. METHODS: Blood cultures were systematically performed in patients suspected of BSI in a referral hospital in Phnom Penh, Cambodia. Data were collected between 1 January 2009 and 31 December 2011. RESULTS: A total of 452 culture-confirmed episodes of BSI were recorded in 435 patients, of whom 17.9% and 82.1% were HIV-positive and HIV-negative, respectively. Escherichia coli accounted for one-third (n = 155, 32.9%) of 471 organisms, with similar rates in both patient groups. Staphylococcus aureus and Salmonella cholereasuis were more frequent in HIV-positive vs. HIV-negative patients (17/88 vs. 38/383 (P = 0.02) and 10/88 vs. 5/383 (P < 0.001)). Burkholderia pseudomallei was more common in HIV-negative than in HIV-positive patients (39/383 vs. 2/88, P < 0.001). High resistance rates among commonly used antibiotics were observed, including 46.6% ceftriaxone resistance among E. coli isolates. Empiric antibiotic treatments were similarly appropriate in both patient groups but did not cover antibiotic-resistant E. coli (both patient groups), S. aureus (both groups) and B. pseudomallei (HIV-negative patients). CONCLUSION: The present data do not warrant different empiric antibiotic regimens for HIV-positive vs. HIV-negative patients in Cambodia. The overall resistance rates compromise the appropriateness of the current treatment guidelines.
    • Dried blood spots are a useful tool for quality assurance of rapid HIV testing in Kigali, Rwanda.

      Chaillet, P; Zachariah, R; Harries, K; Rusanganwa, E; Harries, A D; Médecins sans Frontières, Medical Department, Brussels Operational Center, Belgium. (Published by Elsevier, 2009-06)
      A study was conducted in two primary health facilities in Kigali, Rwanda, to determine whether dried blood spots (DBS) used for quality control of HIV testing would give comparable results with serum after being stored for a period of 14 days and 30 days at ambient temperature. DBS and serum specimens were collected from patients undergoing HIV testing. ELISA performed on serum at baseline (gold standard) was compared with DBS results. The study included a total of 491 patients, comprising 92 (19%) males and 399 (81%) females with a median age of 27 years. A total of 148 individuals (30%) were HIV-positive. The average ambient temperature under which DBS specimens were stored at the health facilities was 23 degrees C (range 18-25 degrees C). The kappa statistic at 14 days and 30 days was 0.99 (99.4% agreement) and 0.98 (99.2% agreement), respectively, signifying almost 'perfect agreement (P<0.001)' with the gold standard. In a resource-limited sub-Saharan African country embarking on scaling-up of HIV testing, DBS stored at ambient conditions for up to 1 month were found to be a useful and robust tool to perform quality control of rapid HIV testing at the health centre level.
    • Driving a decade of change: HIV/AIDS, patents and access to medicines for all

      Hoen, Ellen 't; Berger, Jonathan; Calmy, Alexandra; Moon, Suerie; Medicines Patent Pool Initiative, UNITAID Secretariat, Geneva, Switzerland; SECTION27, Braamfontein, Johannesburg, South Africa; HIV Unit, Division of Infectious Disease, Geneva University Hospital, Geneva, Switzerland; Médecins Sans Frontières Campaign for Access to Essential Medicines, Geneva, Switzerland; Sustainability Science Program, Center for International Development, Kennedy School of Government, Harvard University, Cambridge, MA, USA (BioMed Central, 2011-03-27)
      Since 2000, access to antiretroviral drugs to treat HIV infection has dramatically increased to reach more than five million people in developing countries. Essential to this achievement was the dramatic reduction in antiretroviral prices, a result of global political mobilization that cleared the way for competitive production of generic versions of widely patented medicines.Global trade rules agreed upon in 1994 required many developing countries to begin offering patents on medicines for the first time. Government and civil society reaction to expected increases in drug prices precipitated a series of events challenging these rules, culminating in the 2001 World Trade Organization's Doha Declaration on the Agreement on Trade-Related Aspects of Intellectual Property Rights and Public Health. The Declaration affirmed that patent rules should be interpreted and implemented to protect public health and to promote access to medicines for all. Since Doha, more than 60 low- and middle-income countries have procured generic versions of patented medicines on a large scale.Despite these changes, however, a "treatment timebomb" awaits. First, increasing numbers of people need access to newer antiretrovirals, but treatment costs are rising since new ARVs are likely to be more widely patented in developing countries. Second, policy space to produce or import generic versions of patented medicines is shrinking in some developing countries. Third, funding for medicines is falling far short of needs. Expanded use of the existing flexibilities in patent law and new models to address the second wave of the access to medicines crisis are required.One promising new mechanism is the UNITAID-supported Medicines Patent Pool, which seeks to facilitate access to patents to enable competitive generic medicines production and the development of improved products. Such innovative approaches are possible today due to the previous decade of AIDS activism. However, the Pool is just one of a broad set of policies needed to ensure access to medicines for all; other key measures include sufficient and reliable financing, research and development of new products targeted for use in resource-poor settings, and use of patent law flexibilities. Governments must live up to their obligations to protect access to medicines as a fundamental component of the human right to health.
    • 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.