Community-Based ART Service Delivery for Key Populations in Sub-Saharan Africa: Scoping Review of Outcomes Along the Continuum of HIV Care.

HIV positive key population (KP) often face health system and social barriers to HIV care. KP include sex workers, men who have sex with men, persons who inject drugs, transgender people, and people in prisons and other closed settings. Community-based ART service delivery (CBART) has the potential to increase access to antiretroviral treatment (ART) and enhance retention in care. This scoping review summarized the evidence on the effect of CBART along the continuum of HIV care among KP in sub-Saharan Africa. We searched Pubmed, Web of Science, Google scholar, and NGO websites for articles published between 2010 and April 2020. We synthesized the involvement of KP community members or lay providers in medical task provision, and outcomes along the continuum of HIV care. Of 3,330 records identified, 66 were eligible for full test screening, out of which 12 were included in the review. CBART for KP was provided through: (a) community drop-in-centres, (b) community drop-in-centres plus mobile team, or (c) community-based health centres. KP were engaged as peer educators and they provided services such as community mobilisation activities for HIV testing and ART, ART adherence counselling, and referral for ART initiation. Across the KP-CBART studies, outcomes in terms of ART uptake, adherence to ART, retention in care and viral suppression were at least as good as those obtained for KP attending facility-based care. KP-CBART was as effective as facility-based care. To achieve the UNAIDS 95-95-95 target in sub-Saharan Africa, national programmes should scale-up KP-CBART to complement facility-based care.

Scaling up antiretroviral treatment and improving patient retention in care: lessons from Ethiopia, 2005-2013.

BACKGROUND: Antiretroviral treatment (ART) was provided to more than nine million people by the end of 2012. Although ART programs in resource-limited settings have expanded treatment, inadequate retention in care has been a challenge. Ethiopia has been scaling up ART and improving retention (defined as continuous engagement of patients in care) in care. We aimed to analyze the ART program in Ethiopia. METHODS: A mix of quantitative and qualitative methods was used. Routine ART program data was used to study ART scale up and patient retention in care. In-depth interviews and focus group discussions were conducted with program managers. RESULTS: The number of people receiving ART in Ethiopia increased from less than 9,000 in 2005 to more than 439, 000 in 2013. Initially, the public health approach, health system strengthening, community mobilization and provision of care and support services allowed scaling up of ART services. While ART was being scaled up, retention was recognized to be insufficient. To improve retention, a second wave of interventions, related to programmatic, structural, socio-cultural, and patient information systems, have been implemented. Retention rate increased from 77% in 2004/5 to 92% in 2012/13. CONCLUSION: Ethiopia has been able to scale up ART and improve retention in care in spite of its limited resources. This has been possible due to interventions by the ART program, supported by health systems strengthening, community-based organizations and the communities themselves. ART programs in resource-limited settings need to put in place similar measures to scale up ART and retain patients in care.

How to improve patient retention in an antiretroviral treatment program in Ethiopia: a mixed-methods study.

BACKGROUND: Patient retention, defined as continuous engagement of patients in care, is one of the crucial indicators for monitoring and evaluating the performance of antiretroviral treatment (ART) programs. It has been identified that suboptimal patient retention in care is one of the challenges of ART programs in many settings. ART programs have, therefore, been striving hard to identify and implement interventions that improve their suboptimal levels of retention. The objective of this study was to develop a framework for improving patient retention in care based on interventions implemented in health facilities that have achieved higher levels of retention in care. METHODS: A mixed-methods study, based on the positive deviance approach, was conducted in Ethiopia in 2011/12. Quantitative data were collected to estimate and compare the levels of retention in care in nine health facilities. Key informant interviews and focus group discussions were conducted to identify a package of interventions implemented in the health facilities with relatively higher or improving levels of retention. RESULTS: Retention in care in the Ethiopian ART program was found to be variable across health facilities. Among hospitals, the poorest performer had 0.46 (0.35, 0.60) times less retention than the reference; among health centers, the poorest performers had 0.44 (0.28, 0.70) times less retention than the reference. Health facilities with higher and improving patient retention were found to implement a comprehensive package of interventions: (1) retention promoting activities by health facilities, (2) retention promoting activities by community-based organizations, (3) coordination of these activities by case manager(s), and (4) patient information systems by data clerk(s). On the contrary, such interventions were either poorly implemented or did not exist in health facilities with lower retention in care. A framework to improve retention in care was developed based on the evidence found by applying the positive deviance approach. CONCLUSION: A framework for improving retention in care of patients on ART was developed. We recommend that health facilities implement the framework, monitor and evaluate their levels of retention in care, and, if necessary, adapt the framework to their own contexts.

Nontuberculous mycobacterial disease in patients with HIV in Southeast Asia.

RATIONALE: Although nontuberculous mycobacteria (NTM) are widely documented as a cause of illness among HIV-infected people in the developed world, studies describing the prevalence of NTM disease among HIV-infected people in most resource-limited settings are rare. OBJECTIVES: To evaluate the prevalence of mycobacterial disease in HIV-infected patients in Southeast Asia. METHODS: We enrolled people with HIV from three countries in Southeast Asia and collected pulmonary and extrapulmonary specimens to evaluate the prevalence of mycobacterial disease. We adapted American Thoracic Society/Infectious Disease Society of America guidelines to classify patients into NTM pulmonary disease, NTM pulmonary disease suspects, NTM disseminated disease, and no NTM categories. MEASUREMENTS AND MAIN RESULTS: In Cambodia, where solid media alone was used, NTM was rare. Of 1,060 patients enrolled in Thailand and Vietnam, where liquid culture was performed, 124 (12%) had tuberculosis and 218 (21%) had NTM. Of 218 patients with NTM, 66 (30%) were classified as NTM pulmonary disease suspects, 9 (4%) with NTM pulmonary disease, and 10 (5%) with NTM disseminated disease. The prevalence of NTM disease was 2% (19 of 1,060). Of 51 patients receiving antiretroviral therapy (ART), none had NTM disease compared with 19 (2%) of 1,009 not receiving ART. CONCLUSIONS: Although people with HIV frequently have sputum cultures positive for NTM, few meet a strict case definition for NTM disease. Consistent with previous studies, ART was associated with lower odds of having NTM disease. Further studies of NTM in HIV-infected individuals in tuberculosis-endemic countries are needed to develop and validate case definitions.

Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

BACKGROUND: Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district). METHODS: Retention rates at six-month intervals are reported separately among (1) patients since ART initiation and (2) patients who had been on ART for at least 12 months, according to the site of ART initiation and follow-up, using the Kaplan Meier method. 'Retention' was defined as being alive on ART or transferred out, while 'attrition' was defined as dead, lost to follow-up or stopped ART. RESULTS: In Thyolo and Buhera, a total of 12,004 and 9,721 patients respectively were included in the analysis. The overall retention among the patients since ART initiation was 84%, 80% and 77% in Thyolo and 88%, 84% and 82% in Buhera at 6, 12 and 18 months, respectively. In both programmes the largest drop in ART retention was found during the initial 12 months on ART, mainly related to a high mortality rate in the health centres in Thyolo and a high loss to follow-up rate in the hospital in Buhera. Among the patients who had been on ART for at least 12 months, the retention rates leveled out, with 97%, 95% and 94% in both Thyolo and Buhera, at 18, 24 and 30 months respectively. Loss to follow-up was identified as the main contributor to attrition after 12 months on treatment in both programmes. CONCLUSIONS: To better understand the reasons of attrition and adapt the ART delivery care models accordingly, it is advisable to analyse short and long term retention separately, in order to adapt intervention strategies accordingly. During the initial months on ART more medical follow-up, especially for symptomatic patients, is required to reduce mortality. Once stable on ART, however, the ART care delivery should focus on regular drug refill and adherence support to reduce loss to follow up. Hence, innovative life-long retention strategies, including use of new communication technologies, community based interventions and drug refill outside the health facilities are required.

Melioidosis, phnom penh, Cambodia.

We describe 58 adult patients with melioidosis in Cambodia (2007-2010). Diabetes was the main risk factor (59%); 67% of infections occurred during the rainy season. Bloodstream infection was present in 67% of patients, which represents 12% of all bloodstream infections. The case-fatality rate was 52% and associated with inappropriate empiric treatment.

Time of administration of rabies immunoglobulins and adequacy of antibody response upon post-exposure prophylaxis: a descriptive retrospective study in Belgium.

Background: Data on rabies post-exposure prophylaxis (PEP) and the use of human rabies immunoglobulins (HRIG) in Belgium are scarce. The main objective of this study was to evaluate the timely administration of HRIG after rabies exposure. The secondary objective was to evaluate the adequate antibody response following PEP.Methods: We reviewed all medical records from July 2017 to June 2018 of patients seeking care at, or referred to, the Institute of Tropical Medicine and the University Hospital, Antwerp for the administration of human rabies immunoglobulins following potential rabies exposure abroad or in Belgium.A timely response was defined as starting HRIG with a delay of ≤48 h and rabies vaccination in the first 7 days after exposure.Adequate antibody response was defined as a titer of >5.0 IU/mL in case of bat-related exposure and >3.0 IU/mL in case of exposure to other animals. Titers were measured 10 days after the last PEP vaccine dose, using the rapid fluorescent focus inhibition test (RFFIT).Results: Of the 92 cases treated with HRIG, 75 were evaluated.The majority of injuries were acquired in Asia (n = 26,34%) and in Western Europe (n = 18, 24%), of which 17 in Belgium. The five most frequently recorded countries overseas were Indonesia (n = 13), Thailand (n = 7), Morocco (n = 4), Peru (n = 3) and Costa Rica (n = 3). Administration of immunoglobulins was related to injuries by dogs (36%), monkeys (25%) or bats (22%).A timely response was observed in 16 (21,33%) and in 55 (73,33%) of subjects receiving HRIG (≤48 h) or rabies vaccine (<7days) respectively. The mean time between exposure and the first administered dose of rabies vaccine and HRIG was 7.7 and 8.7 days, respectively. The mean delay for HRIG administration was 9.6 days and 6 days for abroad and inland risks, respectively.In 15 of 16 (94%) bat-related cases the antibody titer after full PEP was >5.0 IU/ml. In 38 of 47 (81%) cases related to other animals the RFFIT titer was >3.0 IU/ml. All low-responders received additional rabies injections.Conclusion: This study showed a substantial time delay between the animal-related risk and the administration of HRIG, in particular when the injury occurred abroad. More targeted communication about the risks of rabies and preventable measures may reduce this delay.Furthermore, the antibody response was inadequate in some cases following full PEP administration according to the Belgian recommendation.

Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

BACKGROUND: About 20-30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation. PRESENTATION OF THE HYPOTHESIS: We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS. TESTING THE HYPOTHESIS: Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS. IMPLICATIONS OF THE HYPOTHESIS: If the role of vitamin D in IRIS is confirmed, we would be able to screen patients at risk for IRIS by screening for vitamin D deficiency. After confirmation by means of a clinical trial, vitamin D supplementation could be a cheap and safe way to reduce the incidence of IRIS.

Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings.

The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important early complication of antiretroviral therapy (ART) in resource-limited settings, especially in patients with tuberculosis. However, there are no consensus case definitions for IRIS or tuberculosis-associated IRIS. Moreover, previously proposed case definitions are not readily applicable in settings where laboratory resources are limited. As a result, existing studies on tuberculosis-associated IRIS have used a variety of non-standardised general case definitions. To rectify this problem, around 100 researchers, including microbiologists, immunologists, clinicians, epidemiologists, clinical trialists, and public-health specialists from 16 countries met in Kampala, Uganda, in November, 2006. At this meeting, consensus case definitions for paradoxical tuberculosis-associated IRIS, ART-associated tuberculosis, and unmasking tuberculosis-associated IRIS were derived, which can be used in high-income and resource-limited settings. It is envisaged that these definitions could be used by clinicians and researchers in a variety of settings to promote standardisation and comparability of data.

HIV viral load monitoring in resource-limited regions: optional or necessary?

Although it is a standard practice in high-income countries, determination of the human immunodeficiency virus (HIV) load is not recommended in developing countries because of the costs and technical constraints. As more and more countries establish capacity to provide second-line therapy, and as costs and technological constraints associated with viral load testing decrease, the question of whether determination of the viral load is necessary deserves attention. Viral load testing could increase in importance as a guide for clinical decisions on when to switch to second-line treatment and on how to optimize the duration of the first-line treatment regimen. In addition, the viral load is a particularly useful tool for monitoring adherence to treatment, performing sentinel surveillance, and diagnosing HIV infection in children aged <18 months. Rather than considering viral load data to be an unaffordable luxury, efforts should be made to ensure that viral load testing becomes affordable, simple, and easy to use in resource-limited settings.

Co-trimoxazole prophylaxis in tropical countries in the era of highly active antiretroviral therapy: do we know enough?

Co-trimoxazole prophylaxis in HIV-infected persons is beyond doubt one of the cheapest and most important interventions, next to antiretroviral therapy (ART), to improve survival. However, many questions, ranging from programme coverage and public health impact to individual tolerance and compliance, remain unanswered. Together with the need for more research to identify optimal ART regimens for resource-poor settings, research regarding optimal chemoprophylaxis against opportunistic infections should also remain high on the agenda.

A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries.

Monitoring the efficacy of antiretroviral treatment in developing countries is difficult because these countries have few laboratory facilities to test viral load and drug resistance. Those that exist are faced with a shortage of trained staff, unreliable electricity supply, and costly reagents. Not only that, but most HIV patients in resource-poor countries do not have access to such testing. We propose a new model for monitoring antiretroviral treatment in resource-limited settings that uses patients' clinical and treatment history, adherence to treatment, and laboratory indices such as haemoglobin level and total lymphocyte count to identify virological treatment failure, and offers patients future treatment options. We believe that this model can make an accurate diagnosis of treatment failure in most patients. However, operational research is needed to assess whether this strategy works in practice.

Demographic and clinical characteristics of HIV-infected inpatients and outpatients at a Cambodian hospital.

A retrospective cross-sectional survey of 299 HIV-infected inpatients and outpatients was conducted between March 1999 and June 2000 in Phnom Penh, Cambodia, to define patient demographics and risk factors for HIV-1 infection, and to compare whether symptoms and opportunistic infections (OIs) differ by gender and site of patient care. The population represented one third of HIV-infected patients regularly receiving care at the Sihanouk Hospital Center of HOPE. Over one quarter (26%) of the men were soldiers and 27% were farmers or laborers. Eighty-nine percent of the men had visited sex workers, 29% of men and women had unsafe injections in the past, and 18% of women reported a spouse who was HIV-positive. Eighty percent of patients presented with weight loss more than 10% from baseline. Seventy-two percent of patients were diagnosed with two or more concurrent OIs or conditions. Oral candidiasis (p = <0.001), abdominal lymphadenitis (p = 0.03), and two or more concurrent OIs (p = <0.001) were diagnosed more often among men than women. Multivariate logistic regression shows that patients who presented with weight loss more than 10% from baseline are more likely to have one or more OIs or conditions. The results of this survey suggest that the primary risk factor for HIV-infected men presenting to this care facility was visiting sex workers. The pattern of OIs and other HIV-associated conditions indicated that the majority of patients delayed seeking care at the hospital. HIV physicians in Cambodia should be aware of the likelihood for multiple OIs or conditions when patients present weight loss more than 10% from baseline.

Remote consultations and HIV/AIDS continuing education in low-resource settings.

BACKGROUND: Telemedicine is a way to support physicians working in resource-poor settings, providing remote consultations and continuing medical education on HIV/AIDS care. METHODS: A hybrid E-mail/web support telemedicine service was created in 2003 at the Institute of Tropical Medicine, Antwerp, Belgium, with a discussion forum hosting more than 170 healthcare professionals from 40 different countries, generally resource constrained. Interesting posts and recurring questions from this discussion forum have been elaborated as case studies or frequently asked questions, available on the website for consultation. Education and support are also provided through interactive quizzes, user-friendly guidelines, and policy documents with a particular focus on HIV/AIDS care in developing countries. RESULTS: From April 2003 to March 2005, 342 questions were sent from over 17 countries in Africa, Asia, and South America. The vast majority of these questions (93%) were patient-oriented, with only 7% being general questions. Of the patient-oriented questions, 49% were related to antiretroviral therapy, and 44% were related to the diagnosis and treatment of opportunistic infections. CONCLUSIONS: Telemedicine is a cheap and effective method of providing clinical support and continuing education to healthcare workers treating HIV-positive patients in resource-poor settings.

Management of Kaposi's sarcoma in resource-limited settings in the era of HAART.

The introduction of highly active antiretroviral therapy (HAART) has changed the natural history of AIDS-associated Kaposi's sarcoma (KS). Although the use of HAART remains limited in low-resource settings, there are global initiatives to make these drugs available to several millions of HIV-infected persons. While there are multiple reports of KS regression during HAART with or without chemotherapy, there is little documentation on KS management in resource-limited settings. In this paper we review current KS treatments available worldwide and discuss the implications of the increased access to antiretrovirals for KS treatment strategies in resource-limited settings.

Comparison of albendazole regimen for prophylaxis of strongyloides hyperinfection in nephrotic syndrome patients on long-term steroids in Cambodia.

Nephrotic syndrome patients on long-term steroids face the risk of having heavy uncomplicated strongyloidiasis or death from its extreme form, the strongyloides hyperinfection. The risk can be minimized if we eradicate the parasite first. We compare a once daily and twice daily albendazole regimen in preventing this potentially fatal complication in 122 patients with nephrotic syndrome.

Severe dyshidrosis in two patients with HIV infection shortly after starting highly active antiretroviral treatment.

The use of highly active antiretroviral therapy (HAART) is the gold-standard treatment for HIV infected patients. We here describe two HIV positive patients whose histories are suggestive for dyshidrosis as an immune reconstitution inflammatory syndrome (IRIS). Several factors have been associated with the exacerbation of dyshidrosis lesions but no direct relationship with HAART has been reported until now.

Telemedicine for HIV/AIDS Care in Low Resource Settings.

Telemedicine is a way to support health care delivery in remote areas. With our telemedicine project the Institute of Tropical Medicine, Antwerp, Belgium, intended to facilitate the introduction of antiretroviral therapy (ART) for patients affected by Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) in developing countries, providing training, distance support and education to healthcare providers working in those settings.