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.

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.

Challenges from Tuberculosis Diagnosis to Care in Community-Based Active Case Finding among the Urban Poor in Cambodia: A Mixed-Methods Study.

BACKGROUND: While community-based active case finding (ACF) for tuberculosis (TB) holds promise for increasing early case detection among hard-to-reach populations, limited data exist on the acceptability of active screening. We aimed to identify barriers and explore facilitators on the pathway from diagnosis to care among TB patients and health providers. METHODS: Mixed-methods study. We administered a survey questionnaire to, and performed in-depth interviews with, TB patients identified through ACF from poor urban settlements in Phnom Penh, Cambodia. Additionally, we conducted focus group discussions and in-depth interviews with community and public health providers involved in ACF, respectively. RESULTS: Acceptance of home TB screening was strong among key stakeholders due to perceived reductions in access barriers and in direct and indirect patient costs. Privacy and stigma were not an issue. To build trust and facilitate communication, the participation of community representatives alongside health workers was preferred. Most health providers saw ACF as complementary to existing TB services; however, additional workload as a result of ACF was perceived as straining operating capacity at public sector sites. Proximity to a health facility and disease severity were the strongest determinants of prompt care-seeking. The main reasons reported for delays in treatment-seeking were non-acceptance of diagnosis, high indirect costs related to lost income/productivity and transportation expenses, and anticipated side-effects from TB drugs. CONCLUSIONS: TB patients and health providers considered home-based ACF complementary to facility-based TB screening. Strong engagement with community representatives was believed critical in gaining access to high risk communities. The main barriers to prompt treatment uptake in ACF were refusal of diagnosis, high indirect costs, and anticipated treatment side-effects. A patient-centred approach and community involvement were essential in mitigating barriers to care in marginalised communities.

Brief Report: Long-term Outcomes and Their Determinants in Patients on Antiretroviral Treatment in Ethiopia, 2005/6-2011/12: A Retrospective Cohort Study.

BACKGROUND: Antiretroviral treatment (ART) programs in many resource-limited settings have expanded treatment toward universal access. Ethiopia is one of the countries that has been scaling up ART toward universal access, but with very few data on long-term outcomes and their determinants. The objective of this study was to identify the level of long-term outcomes and their determinants in patients on ART in Ethiopia. METHODS: A retrospective cohort study was conducted in 3 health facilities (2 hospitals and 1 health center) between July and September, 2014. Loss to follow-up, death, attrition, and retention were the primary outcomes. Data were collected from patient registers and medical records for the period 2005/6-2011/12. RESULTS: A total of 11,731 patients were included in the study. The overall retention rate was 78 per 100 person-months. Retention rates were 82%, 74%, and 72% at 24, 60, and 84 months on ART, respectively. Retention was associated with male sex, adolescent age, marital status, advanced HIV disease, illiteracy, and peer-support services; however, long-term retention was associated independently with only male sex [with adjusted hazard ratio (aHR) 0.68 (0.56 to 0.77)], married patients [with aHR 0.62 (0.54 to 0.72)], and peer-support services [with aHR 1.62 (1.58 to 1.66)]. DISCUSSION AND CONCLUSIONS: ART programs have lost most of their patients during the first 24 months on ART. It is, therefore, imperative that HIV/ART programs ensure people are tested, linked to care, and initiated on ART early. ART programs should also design and implement interventions, including peer-support services, which are targeted to male, adolescent, unmarried, and illiterate patients.

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.

Bloodstream infection among adults in Phnom Penh, Cambodia: key pathogens and resistance patterns.

BACKGROUND: Bloodstream infections (BSI) cause important morbidity and mortality worldwide. In Cambodia, no surveillance data on BSI are available so far. METHODS: From all adults presenting with SIRS at Sihanouk Hospital Centre of HOPE (July 2007-December 2010), 20 ml blood was cultured. Isolates were identified using standard microbiological techniques; antibiotic susceptibilities were assessed using disk diffusion and MicroScan®, with additional E-test, D-test and double disk test where applicable, according to CLSI guidelines. RESULTS: A total of 5714 samples from 4833 adult patients yielded 501 clinically significant organisms (8.8%) of which 445 available for further analysis. The patients' median age was 45 years (range 15-99 y), 52.7% were women. HIV-infection and diabetes were present in 15.6% and 8.8% of patients respectively. The overall mortality was 22.5%. Key pathogens included Escherichia coli (n = 132; 29.7%), Salmonella spp. (n = 64; 14.4%), Burkholderia pseudomallei (n = 56; 12.6%) and Staphylococcus aureus (n = 53; 11.9%). Methicillin resistance was seen in 10/46 (21.7%) S. aureus; 4 of them were co-resistant to erythromycin, clindamycin, moxifloxacin and sulphamethoxazole-trimethoprim (SMX-TMP). We noted combined resistance to amoxicillin, SMX-TMP and ciprofloxacin in 81 E. coli isolates (62.3%); 62 isolates (47.7%) were confirmed as producers of extended spectrum beta-lactamase. Salmonella isolates displayed high rates of multidrug resistance (71.2%) with high rates of decreased ciprofloxacin susceptibility (90.0%) in Salmonella Typhi while carbapenem resistance was observed in 5.0% of 20 Acinetobacter sp. isolates. CONCLUSIONS: BSI in Cambodian adults is mainly caused by difficult-to-treat pathogens. These data urge for microbiological capacity building, nationwide surveillance and solid interventions to contain antibiotic resistance.

Rapid diagnostic tests for neurological infections in central Africa.

Infections are a leading cause of life-threatening neuropathology worldwide. In central African countries affected by endemic diseases such as human African trypanosomiasis, tuberculosis, HIV/AIDS, and schistosomiasis, delayed diagnosis and treatment often lead to avoidable death or severe sequelae. Confirmatory microbiological and parasitological tests are essential because clinical features of most neurological infections are not specific, brain imaging is seldom feasible, and treatment regimens are often prolonged or toxic. Recognition of this diagnostic bottleneck has yielded major investment in application of advances in biotechnology to clinical microbiology in the past decade. We review the neurological pathogens for which rapid diagnostic tests are most urgently needed in central Africa, detail the state of development of putative rapid diagnostic tests for each, and describe key technical and operational challenges to their development and implementation. Promising field-suitable rapid diagnostic tests exist for the diagnosis of human African trypanosomiasis and cryptococcal meningoencephalitis. For other infections-eg, syphilis and schistosomiasis-highly accurate field-validated rapid diagnostic tests are available, but their role in diagnosis of disease with neurological involvement is still unclear. For others-eg, tuberculosis-advances in research have not yet yielded validated tests for diagnosis of neurological disease.

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.

Azithromycin and ciprofloxacin resistance in Salmonella bloodstream infections in Cambodian adults.

BACKGROUND: Salmonella enterica is a frequent cause of bloodstream infection (BSI) in Asia but few data are available from Cambodia. We describe Salmonella BSI isolates recovered from patients presenting at Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia (July 2007-December 2010). METHODOLOGY: Blood was cultured as part of a microbiological prospective surveillance study. Identification of Salmonella isolates was performed by conventional methods and serotyping. Antibiotic susceptibilities were assessed using disk diffusion, MicroScan and E-test macromethod. Clonal relationships were assessed by Pulsed Field Gel Electrophoresis; PCR and sequencing for detection of mutations in Gyrase and Topoisomerase IV and presence of qnr genes. PRINCIPAL FINDINGS: Seventy-two Salmonella isolates grew from 58 patients (mean age 34.2 years, range 8-71). Twenty isolates were identified as Salmonella Typhi, 2 as Salmonella Paratyphi A, 37 as Salmonella Choleraesuis and 13 as other non-typhoid Salmonella spp. Infection with human immunodeficiency virus (HIV) was present in 21 of 24 (87.5%) patients with S. Choleraesuis BSI. Five patients (8.7%) had at least one recurrent infection, all with S. Choleraesuis; five patients died. Overall, multi drug resistance (i.e., co-resistance to ampicillin, sulphamethoxazole-trimethoprim and chloramphenicol) was high (42/59 isolates, 71.2%). S. Typhi displayed high rates of decreased ciprofloxacin susceptibility (18/20 isolates, 90.0%), while azithromycin resistance was very common in S. Choleraesuis (17/24 isolates, 70.8%). Two S. Choleraesuis isolates were extended spectrum beta-lactamase producer. CONCLUSIONS AND SIGNIFICANCE: Resistance rates in Salmonella spp. in Cambodia are alarming, in particular for azithromycin and ciprofloxacin. This warrants nationwide surveillance and revision of treatment guidelines.

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.

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.

Performance of abdominal ultrasound for diagnosis of tuberculosis in HIV-infected persons living in Cambodia.

BACKGROUND: In resource-limited settings, abdominal ultrasound is often used to assist the diagnosis of tuberculosis (TB) in people with HIV (PLHIV), although data on performance characteristics are missing. METHODS: Cross-sectional study of PLHIV in Cambodia receiving a standardized TB diagnostic evaluation, including history, physical examination, chest radiography, microscopy and culture of various specimens, and abdominal ultrasound. Patients with at least one specimen culture positive for Mycobacterium tuberculosis were classified as having TB. RESULTS: TB was diagnosed in 37 (18%) of 212 PLHIV. Abdominal ultrasound was abnormal in 15 of 37 (41%) patients with TB compared with 14 of 175 (8%) without TB (P < 0.01). Predictors of TB disease included multiple enlarged (1.2 cm or greater) abdominal lymph nodes on ultrasound (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 1.8-22.4), abnormal chest radiography (OR, 6.8; CI, 2.7-17.0), anorexia (OR, 4.6; CI, 1.8-11.7), and CD4 less than 200 cells/mm (OR, 3.3; CI, 1.2-9.1). Having multiple enlarged abdominal lymph nodes on ultrasound was 97.1% (CI, 93.5%-99.1%) specific for TB with a positive likelihood ratio of 11.4 (CI, 4.3-30.3). CONCLUSIONS: Abdominal ultrasound is a useful diagnostic test for TB disease in PLHIV, increasing the posttest probability of TB when multiple enlarged abdominal lymph nodes are visualized. Its wider use may accelerate access to TB treatment, potentially reducing mortality in PLHIV.

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.

Fever after a stay in the tropics: clinical spectrum and outcome in HIV-infected travelers and migrants.

OBJECTIVE: To investigate the epidemiology and clinical spectrum of fever in HIV-infected returning travelers and migrants. METHODS: From April 2000 to December 2006, we explored prospectively, at our referral travel/HIV clinics, the etiology and outcome of febrile illnesses developing within 3 months after a stay in the tropics. For this study, we compared the morbidity profile between HIV-infected individuals and all other cases tested HIV negative. RESULTS: Of the 1850 adults (15 years and older) evaluated for 1921 fever episodes, 93 (5%) had HIV infection, including 5 presenting with primary infection. HIV prevalence was 2% in western travelers or expatriates, 11% in travelers "visiting friends and relatives," and 24% in foreign visitors/migrants. Fever episodes (n = 104) occurring in the HIV-infected individuals were mainly due to opportunistic infections (23%, including tuberculosis), respiratory tract infections (20%), sexually transmitted infections (9%), and noninfectious diseases (7%). All these conditions were more frequently diagnosed than in HIV-negative travelers (1035 fever episodes), although tropical infections (mostly malaria) were proportionally less prevalent. Morbidity (rate and duration of hospitalization) was more considerable in HIV-infected patients than in HIV-negative individuals. CONCLUSIONS: HIV infection was frequent in returning travelers and migrants presenting with fever at our setting and affected strongly the diagnostic spectrum and overall morbidity.

Prevention and treatment of the immune reconstitution inflammatory syndrome.

PURPOSE OF REVIEW: The immune reconstitution inflammatory syndrome occurs in a proportion of HIV-infected patients initiated on combination antiretroviral therapy and results from dysregulated inflammatory responses driven by the recovering immune system. Infective forms may manifest as the unmasking of preexisting untreated opportunistic infections or the paradoxical clinical deterioration of appropriately treated opportunistic infections. The prevention and treatment of this condition is the focus of much research attention, which is the scope of this review. RECENT FINDINGS: Approaches to prevention are informed by studies that have reported on risk factors, particularly those that are modifiable. Two key ongoing research issues are optimal screening for opportunistic infections prior to combination antiretroviral therapy in order to prevent unmasking forms and the optimal timing of combination antiretroviral therapy in patients on treatment for an opportunistic infection, balancing the risk of paradoxical immune reconstitution inflammatory syndrome that is associated with early initiation with the risk of advancing immunosuppression associated with delaying. In most cases of immune reconstitution inflammatory syndrome combination antiretroviral therapy has been continued. A variety of additional management strategies have been used including corticosteroids, nonsteroidal anti-inflammatory drugs, drainage procedures and surgery. The advantages and disadvantages of different management strategies are discussed. SUMMARY: No controlled clinical trials regarding the prevention or treatment of immune reconstitution inflammatory syndrome have been completed. There is a need for such studies in order to guide clinicians in their approach to this condition.