Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: a comparison of three prospective cohorts.

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/µL, respectively) than the HIV-infected control cohort (233 cells/µL) 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.

Epidemiology of HIV-Associated Lung Disease in the United States.

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.

Scale-up of HIV Viral Load Monitoring--Seven Sub-Saharan African Countries.

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.

Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America.

In May 2013, a revised and updated version of the Centers for Disease Control and Prevention/National Institutes of Health/HIV Medicine Association Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents was released online. These guidelines, since their inception in 1989, have been widely accessed in the United States and abroad. These guidelines have focused on the management of HIV/AIDS-related opportunistic infections that occur in the United States. In other parts of the world, the spectrum of complications may be different and the resources available for diagnosis and management may not be identical to those in the United States. The sections that have been most extensively updated are those on immune reconstitution inflammatory syndrome, tuberculosis, hepatitis B, hepatitis C, human papillomavirus, and immunizations. The guidelines will not be published in hard copy form. This document will be revised as needed throughout each year as new data become available.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

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.

Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America.

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.

What's new in the 2009 US guidelines for prevention and treatment of opportunistic infections among adults and adolescents with HIV?

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.

Cost-effectiveness of HIV treatment in resource-poor settings--the case of Côte d'Ivoire.

BACKGROUND: As antiretroviral therapy is increasingly used in settings with limited resources, key questions about the timing of treatment and use of diagnostic tests to guide clinical decisions must be addressed. METHODS: We assessed the cost-effectiveness of treatment strategies for a cohort of adults in Côte d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log copies per milliliter). Using a computer-based simulation model that incorporates the CD4 cell count and HIV RNA level as predictors of disease progression, we compared the long-term clinical and economic outcomes associated with no treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral therapy alone, and prophylaxis with antiretroviral therapy. RESULTS: Undiscounted gains in life expectancy ranged from 10.7 months with antiretroviral therapy and prophylaxis initiated on the basis of clinical criteria to 45.9 months with antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis alone. The incremental cost per year of life gained was 240 dollars (in 2002 U.S. dollars) for prophylaxis alone, 620 dollars for antiretroviral therapy and prophylaxis without CD4 testing, and 1,180 dollars for antiretroviral therapy and prophylaxis with CD4 testing, each compared with the next least expensive strategy. None of the strategies that used antiretroviral therapy alone were as cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis. Life expectancy was increased by 30% with use of a second line of antiretroviral therapy after failure of the first-line regimen. CONCLUSIONS: A strategy of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the use of clinical criteria alone or in combination with CD4 testing to guide the timing of treatment, is an economically attractive health investment in settings with limited resources.

Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/µL: A Stepped-Wedge, Cluster-Randomized Trial.

BACKGROUND: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS. METHODS: We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. RESULTS: We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-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 6-month mortality than patients with titers <1:160. CONCLUSIONS: We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.

Implementation and Operational Research: Impact of Nurse-Targeted Care on HIV Outcomes Among Immunocompromised Persons: A Before-After Study in Uganda.

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 antiretroviral therapy (ART) initiation and retention among severely immunocompromised HIV-infected persons. METHODS: The study included ART-naive patients with CD4 counts <100 cells per microliter 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, 1 additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation, and trace those who were lost 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 the likelihood of retention in the nurse counselor cohort (relative risk: 1.21, 95% CI: 1.09 to 1.34) compared with the routine care cohort was observed. CONCLUSIONS: 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.

Estimated Prevalence of Cryptococcus Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment.

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-naïve adults with a CD4+ count <100 cells/µL 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/µL were sampled and tested for CrAg using the IMMY® 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/µL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/µL and 100-200 cells/µL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/µL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/µL 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/µL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/µL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.

Clinical impact and cost-effectiveness of co-trimoxazole prophylaxis in patients with HIV/AIDS in Côte d'Ivoire: a trial-based analysis.

BACKGROUND: In 2000, WHO/UNAIDS recommended co-trimoxazole prophylaxis for persons at early stages of HIV infection (WHO stage > or = 2) in sub-Saharan Africa. OBJECTIVE: To assess the cost-effectiveness of alternative strategies for initiation of co-trimoxazole in Côte d'Ivoire. DESIGN: Cost-effectiveness analysis with an HIV simulation model using clinical and cost data from a randomized trial of co-trimoxazole in HIV-infected adults. METHODS: The study included HIV-infected patients in Côte d'Ivoire, with median age 33 years. Thirty-four percent were classified as WHO stage 2, 59% as stage 3, and 7% as stage 4. The mean CD4 cell count was 331 x 10(6) cells/l. The interventions were no prophylaxis, clinical criteria-based co-trimoxazole initiation (early: WHO stage > or = 2; late: WHO stage > or = 3), CD4-based co-trimoxazole initiation (< 500, < 200, < 50 x 10(6) CD4 cells/l). The outcome measures were life expectancy, lifetime costs, and incremental cost-effectiveness. RESULTS: The most effective strategy, initiation of co-trimoxazole prophylaxis at WHO stage > or = 2, increased undiscounted life expectancy by 5.2 months, discounted life expectancy by 4.4 months, and lifetime costs by US dollars 60, compared with no prophylaxis. Delaying prophylaxis initiation until WHO stage >or = 3 was less costly and less effective. All CD4-based strategies were dominated. The incremental cost-effectiveness of early versus late co-trimoxazole prophylaxis initiation was US dollars 200/year of life gained. Results were stable despite wide variations in plausible assumptions about bacterial resistance and the prophylaxis efficacy on co-trimoxazole-resistant strains. CONCLUSIONS: For HIV-infected adults in Côte d'Ivoire, co-trimoxazole prophylaxis is reasonably cost-effective and most effective if initiated when WHO stage > or = 2. Early co-trimoxazole prophylaxis will prevent complications prior to antiretroviral therapy initiation and should be considered an essential component of care for early HIV in sub-Saharan Africa.

Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America.

The National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, and CDC have developed guidelines for treatment of opportunistic infections (OIs) among adults and adolescents infected with human immunodeficiency virus (HIV). These guidelines are intended for clinicians and other health-care providers who care for HIV-infected adults and adolescents, including pregnant women; they complement companion guidelines for treatment of OIs among HIV-infected children and previously published guidelines for prevention of OIs in these populations. They include evidence-based guidelines for treatment of 28 OIs caused by protozoa, bacteria, fungi, and viruses, including certain OIs endemic in other parts of the world but that might be observed in patients in the United States. Each OI section includes information on epidemiology, clinical manifestations, diagnosis, treatment recommendations, monitoring and adverse events, management of treatment failure, prevention of recurrence, and special considerations in pregnancy. Tables address drugs and doses, drug toxicities, drug interactions, adjustment of drug doses in persons with reduced renal function, and data about use of drugs in pregnant women.

Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii pneumonia: using simulation modeling to inform clinical guidelines.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis. METHODS: A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/microL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/microL. Data were from randomized controlled trials and other published literature. RESULTS: For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/microL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY. CONCLUSIONS: Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/microL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone.

Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America.

In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children.

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general, treatment should be offered to persons who have <350 CD4+ T cells/mm3 or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replicatioing a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website ( http://www.hivatis.org ).

Assessment of the impact of cotrimoxazole prophylaxis on key outcomes among HIV-infected adults in low- and middle-income countries: a systematic review.

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.