Current World Health Organization (WHO) guidelines recommend cryptococcal antigen (CrAg) screening in blood among those human immunodeficiency virus (HIV)-infected persons not receiving effective antiretroviral therapy (ART), with CD4 values <100 cells/µL, and to consider testing those not on ART with CD4 values between 100–200 cells/µL [1]. This recommendation is based on prior studies demonstrating that a “screen-and-treat” program identifying CrAg-positive persons and giving preemptive fluconazole therapy, in combination with an ART adherence intervention, prevents invasive cryptococcal disease and death [2].

BACKGROUND: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and pre-emptive fluconazole therapy, as an adjunct to antiretroviral therapy (ART), on six-month survival among persons with advanced HIV disease. METHODS: We enrolled HIV-infected, ART-naive eligible participants with <100 CD4 cells/microL, in a stepped-wedge, cluster-randomized trial from July 2012 - December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with lab-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg-positive participants received preemptive fluconazole therapy for ten weeks. We assessed six-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. RESULTS: We included 1,280 observational and 2,108 interventional participants, of whom 9.3% (195/2,108) were CrAg-positive. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (HR = 1.34; 95% CI, 0.86-2.10; P = 0.20), including when the analysis was limited to persons who started ART (HR=1.11; 95% CI, 0.62 - 1.79, P=0.86) However, six-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers >/=1:160 had 2.6-fold higher six-month mortality than patients with titers <1:160. CONCLUSION: We observed no overall survival benefit of the lab-based reflexive CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis appeared to be effective in patients with CrAg titer <1:160. A more aggressive approach may be required for persons with CrAg titer >/=1:160.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

BACKGROUND: HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia. METHODS: Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants. RESULTS: Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/muL, respectively) than the HIV-infected control cohort (233 cells/muL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001). CONCLUSION: Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.

BACKGROUND: Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naive adults with a CD4+ count <100 cells/muL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies. METHODS: The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/muL were sampled and tested for CrAg using the IMMY(R) Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. RESULTS: A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32-46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/muL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/muL and 100-200 cells/muL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/muL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/muL 50-200 (2.2%). CONCLUSION: This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/muL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/muL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.

INTRODUCTION: Improving HIV outcomes among severely immunocompromised HIV-infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic- based nurse care on ART initiation and retention among severely immunocompromised HIV-infected persons. METHODS: The study included ART-naive patients with CD4<100 cells/microL registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, one additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation and trace those loss-to-follow-up. We compared time to ART initiation and 6-month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention. RESULTS: The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (p<0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (p=0.001). A 21% increase in likelihood of retention in the nurse counselor cohort (relative risk 1.21, 95% CI, 1.09-1.34) compared with the routine care cohort was observed. CONCLUSION: Implementation of targeted nurse-led care of severely immunocompromised HIV-infected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention.

The epidemiology of HIV infection and its pulmonary complications in the United States has evolved significantly over nearly 20 years since the advent of combination antiretroviral therapy. While infectious complications are less of a threat to patients whose immune systems have been restored, many HIV-infected persons in the United States remain at high risk for opportunistic infection because they are unaware of their HIV infection, have difficulty maintaining linkage to care, or maintain inadequate viral control. Bacterial pneumonia and Pneumocystis pneumonia remain significantly more prevalent among HIV-infected persons, and together with seasonal influenza are areas where public health efforts to increase antiretroviral therapy, appropriate prophylaxis, and vaccination may decrease burden of disease. Noninfectious pulmonary complications of chronic HIV infection are increasingly recognized in the United States and elsewhere. Chronic obstructive pulmonary disease, asthma, pulmonary hypertension, sleep-disordered breathing, and primary lung cancer may all be more common among persons with HIV; of concern, disease burden in U.S. HIV-infected persons may be underestimated due to lack of diagnostic testing for these conditions. Smoking is among the most prevalent preventable causes of morbidity and mortality affecting persons living with HIV infection, and has particular import to pulmonary disease. As of 2009, 42% of HIV-infected adults in medical care in the United States smoked tobacco (over twice the national rate in the general population). Successful efforts to promote smoking cessation among HIV-infected persons are of critical importance to decrease the burden of chronic pulmonary disease.

To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring.

We thank Harding et al for their attention to our supplement and for acknowledging the need to prioritize HIV care and support interventions for maximum impact. We appreciate the opportunity to address the issues raised regarding the methods used in the evidence reviews in the supplement and the overall conclusions. | The introductory article in the supplement1 explains the process used in performing these reviews. Selection of articles involved a 3-step process: (1) the total number of citations from the CDC Library (and other sources, if applicable), (2) the number of abstracts that were deemed eligible for review of the full-text articles (eligible studies), and (3) the number of studies that fulfilled the inclusion criteria upon review of the full-text articles (included studies). These steps are those specified by the Preferred Reporting Items for Systematic Reviews and Meta-Analyse guidelines.2 Details, including search terms used for the literature review and flow diagrams, are included in each of the intervention-specific articles in the supplement. The introductory article explains the rating systems used for the quality of evidence of individual studies, and for the overall quality of the body of evidence and expected impact, of each intervention for each of the specific outcomes of interest. The rating system of the overall quality of evidence was adapted from that used by the US Preventive Services Task Force, as indicated

INTRODUCTION: Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose. METHODS: We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163. FINDINGS: 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0.40, 95% CI 0.26-0.64) when started at CD4 counts of 350 cells per muL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per muL without ART reduced rates of death (0.50, 0.30-0.83) and malaria (0.25, 0.10-0.57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0.05, 95% CI -0.12 to 0.02), low birthweight (0.00, -0.07 to 0.07), and placental malaria (0.00, -0.10 to 0.10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per muL reduced admittances to hospital (HR 0.42, 95% CI 0.22-0.80), pneumonia (0.73, 0.61-0.88), malaria (0.03, 0.01-0.10), and diarrhoea (0.61, 0.48-0.78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0.07, 95% CI -0.52 to 0.39). INTERPRETATION: Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per muL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. FUNDING: None.

Guidelines for antiretroviral (ARV) prophylaxis following high-risk exposure (postexposure prophylaxis—PEP) to human immunodeficiency virus (HIV) date to 1990, when the US Centers for Disease Control and Prevention (CDC) first considered such recommendations for persons with occupational exposures to HIV [1]. The US Public Health Service also issued recommendations focused on occupational exposures in 1996 [2]; these recommendations have been updated 5 times [3–7]. Prophylaxis after non-occupational exposures to HIV (via sexual contact and sharing of drug-using paraphernalia) was first addressed by the CDC in 1998 [8] and updated in 2005 [9]. The World Health Organization (WHO) first considered PEP in 2007 and included PEP recommendations in the 2013 consolidated guidelines; both documents focused on occupational exposures [10, 11]. The most recently published WHO guidelines on PEP recommend that a PEP regimen be administered as soon as possible within the 72-hour window period after an HIV-related exposure and that whereas a 2-drug antiretroviral regimen is acceptable, a 3-drug regimen is preferred [12].

As of December 2012, an estimated 35.3 million persons were living with HIV; approximately two thirds of these people were living in sub-Saharan Africa.1 The response to the HIV pandemic in Africa and in other low-and middle-income regions of the world has consisted of a variety of bilateral and multi-lateral support from donor agencies, as well as local support from countries that have been able to afford it. A majority of the support has been directed towards HIV care and treatment. | Accordingly, the past ten years have witnessed a remarkable increase in the number of HIV-infected persons receiving antiretroviral therapy (ART) in low- and middle-income countries--from 300,000 in 2003 to 9.7 million in 20121,2. Expanded access to ART in these countries has led to significant proportions of eligible persons enrolled on ART, reaching coverage rates as high as 61% based on the World Health Organization (WHO) treatment guidelines eligibility criteria of CD4 <350 cells/uL) in 2012.1 In 2013, WHO revised its guidelines to indicate eligibility at CD4 <500 cells/uL; under these criteria, only 34% of eligible persons were on ART in 2013.1 Nevertheless, these changes in access to ART were estimated to have averted 4.2 million deaths through 20122.1 | HIV treatment programs in low- and middle-income countries have been supported by a variety of sources, including over $50 billion through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from 2004 to 20133. PEPFAR programs are coordinated by the U.S. Department of State’s Office of the U.S. Global AIDS Coordinator (OGAC) in Washington, D.C.,; oversight of in-country expenditures is supported by additional U.S. government(USG) agencies with the majority of funds concentrated in 36 countries and regions 4 in sub-Saharan Africa, South and Central Asia, Eastern Europe, Central America and the Caribbean. PEPFAR supports a range of HIV care and treatment services besides ART including clinical (e.g. monitoring to determine eligibility for ART and prevention and treatment of opportunistic infections) and non-clinical services (e.g. psychological, social, and preventive)4. Services implemented through PEPFAR support in each country are determined through a dialogue between the USG, and host governments. PEPFAR country operating plans and budgets are submitted annually and reviewed by USG staff.

BACKGROUND: Cotrimoxazole (CTX) prophylaxis is among the key interventions provided to HIV-infected individuals in resource-limited settings. We conducted a systematic review of the available evidence. METHODS: MEDLINE, Embase, Global Health, CINAHL, SOCA, and African Index Medicus (AIM) were used to identify articles relevant to the CTX prophylaxis intervention from 1995 to 2014. Included articles addressed impact of CTX prophylaxis on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated the quality of evidence in individual articles and assessed the overall quality of the body of evidence, the expected impact, and the cost effectiveness (CE) for each outcome. RESULTS: Of the initial 1418 identified articles, 42 met all inclusion criteria. These included 9 randomized controlled trials, 26 observational studies, 2 systematic reviews with meta-analysis, 1 other systematic review, and 4 CE studies. The overall quality of evidence was rated as "good" and the expected impact "high" for both mortality and morbidity. The overall quality of evidence from the 4 studies addressing retention in care was rated as "poor," and the expected impact on retention was rated as "uncertain." The 4 assessed CE studies showed that provision of CTX prophylaxis is cost effective and sometimes cost saving. No studies addressed impact on quality of life or HIV transmission. CONCLUSIONS: CTX prophylaxis is a cost-effective intervention with expected high impact on morbidity and mortality reduction in HIV-infected adults in resource-limited settings. Benefits are seen in both pre-antiretroviral therapy and antiretroviral therapy populations.

BACKGROUND: Screening individuals with AIDS for serum cryptococcal antigen (CrAg), followed by treatment of CrAg positives with antifungals, may prevent cryptococcal meningitis. This review examined data on CrAg screening and treatment in resource-limited settings. METHODS: We searched articles published during 2007-2014 on the effectiveness and cost-effectiveness of CrAg screening and treatment on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated overall quality of individual articles, summarized the body of evidence, the expected impact, and cost-effectiveness for each outcome. RESULTS: We identified 2613 articles. Eight met all inclusion criteria. Five studies addressed mortality and/or morbidity outcomes; all were observational and had small sample sizes; 3 lacked a comparison group. Ratings of study quality ranged from "medium" to "weak," and the quality of the overall body of evidence for mortality and morbidity outcomes was rated as "fair." The intervention's expected impact on mortality and morbidity was rated as "moderate." The 4 cost-effectiveness studies included in the analysis showed that CrAg screening and treatment interventions are highly cost-effective. No studies addressed retention in care, quality of life, or HIV transmission. CONCLUSIONS: Although limited, the body of evidence regarding CrAg screening and treatment suggests that the intervention may have an impact on preventing cryptococcal meningitis and death in persons with AIDS. Additional research is needed to quantify the intervention's effectiveness and identify optimal treatment dosing and implementation best practices.

The number of persons living with HIV worldwide reached approximately 35.3 million in 2012. Meanwhile, AIDS-related deaths and new HIV infections have declined. Much of the increase in HIV prevalence is from rapidly increasing numbers of people on antiretroviral treatment who are now living longer. There is regional variation in epidemiologic patterns, major modes of HIV transmission, and HIV program response. It is important to focus on HIV incidence, rather than prevalence, to provide information about HIV transmission patterns and populations at risk. Expanding HIV treatment will function as a preventive measure through decreasing horizontal and vertical transmission of HIV.

Many guidelines, including those produced by the World Health Organisation (WHO), have failed to adhere to rigorous methodological standards. Operational examples of guideline development processes may provide important lessons learned to improve the rigour and quality of future guidelines. To this end, this paper describes the process of developing WHO guidelines on prevention and care interventions for adults and adolescents living with HIV. Using a pragmatic, structured, evidence-based approach, we created an organising committee, identified topics, conducted systematic reviews, identified experts and distributed evidence summaries. Subsequently, 55 global HIV experts drafted and anonymously submitted guideline statements at the beginning of a conference. During the conference, participants voted on statements using scales evaluating appropriateness of the statements, strength of recommendation and level of evidence. After review of voting results, open discussion, re-voting and refinement of statements, a draft version of the guidelines was completed. A post-conference writing team refined the guidelines based on pre-determined guideline writing principles and incorporated external comments into a final document. Successes and challenges of the guideline development process were identified and are used to highlight current issues and debates in developing guidelines with a focus on implications for future guideline development at WHO.

This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003-2008 has been incorporated into this document.

Despite dramatic declines in the incidence of opportunistic infections (OIs) in the United States, they remain an important cause of morbidity and mortality for HIV-infected persons. Previously separate guidelines on the prevention of OIs and on the treatment of OIs have been combined recently into an updated single document; the present article reviews salient changes to and new information contained in this guidance. Chapters on hepatitis B virus infection and tuberculosis have been expanded substantially, and each chapter now includes information on immune reconstitution inflammatory syndrome. In addition, there is detailed discussion on the role of antiretroviral therapy in OI prevention and issues concerning the initiation of antiretroviral therapy during treatment of an acute OI. In the future, these guidelines will likely be maintained as an internet-based document to facilitate wider dissemination and more rapid updates.