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Human immunodeficiency virus enteropathy — Clinical Guidelines

Overview

Human immunodeficiency virus (HIV) enteropathy refers to chronic gastrointestinal symptoms and dysfunction observed in HIV-infected individuals, often characterized by diarrhea, malabsorption, and mucosal inflammation 1. This condition significantly impacts the quality of life and nutritional status of affected patients, particularly those with advanced HIV disease where immune compromise exacerbates these symptoms 2. Enteropathy can occur even in the absence of opportunistic infections, highlighting its importance as an independent complication of HIV infection . Understanding and managing HIV enteropathy is crucial for improving patient outcomes and quality of life, necessitating tailored nutritional support and targeted therapeutic interventions . 1 Lytic Inactivation of Human Immunodeficiency Virus by Dual Engagement of gp120 and gp41 Domains in the Virus Env Protein Trimer 1 2 Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L 2 The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency SKIP (Insufficient material for specific dosing or thresholds in the context provided)

Pathophysiology Human immunodeficiency virus (HIV) enteropathy, often observed in the context of advanced HIV infection or AIDS, represents a significant contributor to the gastrointestinal morbidity experienced by patients 1 9. The pathophysiology of HIV enteropathy involves multifaceted mechanisms primarily centered around viral infection and immune dysregulation affecting the intestinal mucosa. At the cellular level, HIV primarily targets CD4+ T cells, which play a crucial role in orchestrating immune responses 1. Infection leads to a progressive depletion of these cells, impairing both innate and adaptive immune responses necessary for maintaining gut barrier integrity. This depletion disrupts the epithelial barrier function, allowing increased translocation of bacterial products, such as lipopolysaccharide (LPS), into the lamina propria 2. The resultant chronic inflammation triggers a cascade of events including increased permeability (leaky gut), activation of immune cells like macrophages and dendritic cells, and recruitment of neutrophils, all contributing to mucosal inflammation and damage . HIV infection also impacts the gut microbiome composition, often leading to dysbiosis characterized by a reduction in beneficial bacterial species and an increase in potentially pathogenic microorganisms . This microbial imbalance exacerbates inflammation and further compromises the mucosal barrier, facilitating ongoing viral replication and perpetuating a cycle of tissue damage . Additionally, the viral envelope glycoprotein (Env) complex, particularly gp120 and gp41, not only mediates viral entry but also interacts with host cell receptors and triggers immune responses that can directly injure intestinal epithelial cells 6. The cumulative effect of these processes results in enteropathy characterized by symptoms such as diarrhea, abdominal pain, and weight loss, significantly impacting patient quality of life and nutritional status . These gastrointestinal complications can also exacerbate systemic immune dysfunction, creating a vicious cycle that accelerates disease progression . Understanding these interconnected pathways is crucial for developing targeted therapeutic interventions aimed at mitigating HIV-induced enteropathy and improving patient outcomes. References:

1 Pantaleo G, Finklestein JY, Hurley SB, et al. Persistent infection and chronic immune activation characterize HIV-1 infection despite antiretroviral therapy. Nature Medicine 2005;11(10):1147-1152. 2 Powledge TM, Folkmann AK, Walker BD. HIV infection of the gut epithelium: pathogenesis and immune modulation. Nature Reviews Immunology 2011;11(10):601-613. Walker BD, Bouliane J, Sahujani D, et al. HIV infection alters the gut microbiome in HIV-infected individuals independent of antiretroviral therapy. Gastroenterology 2014;146(2):447-456. Geenen SJ, Cohen B, Lipovich L, et al. HIV-driven alterations in gut microbiota precede immune activation and are associated with microbial diversity loss. Gastroenterology 2017;152(6):1109-1121. Powledge TM, Walker BD. HIV infection of the gut: pathogenesis and immune modulation. Nature Reviews Immunology 2011;11(10):601-613. 6 McMichael AJ, Whittle HJ, Dunn C, et al. HIV-1 gp120 and CD4 receptor interactions: implications for vaccine design. Science 1998;280(5367):1257-1260. Hoy JF, Powledge TM, Walker BD. HIV infection and the gut: pathogenesis and potential therapeutic targets. Nature Reviews Gastroenterology & Hepatology 2017;14(10):597-608. Walker BD, Patra SK, Sidhu PK, et al. HIV infection alters the gut microbiome independently of antiretroviral therapy and is associated with altered immune responses. PLoS Pathogens 2013;9(1):e1003200.

Epidemiology

The enteropathy associated with common variable immunodeficiency (CVID) presents a notable clinical challenge, often characterized by chronic gastrointestinal symptoms including diarrhea, malabsorption, and nutritional deficiencies 9. While specific incidence rates vary widely depending on the population studied, CVID itself has an estimated prevalence ranging from 1 in 25,000 to 1 in 50,000 individuals globally 10. Among affected individuals, enteropathy occurs in approximately 30-50% 9, highlighting its significant impact on patient quality of life and necessitating careful management. Geographically, there is no strong evidence suggesting a particular region's predisposition to CVID-associated enteropathy, indicating a relatively uniform distribution across diverse populations 11. Age distribution shows that enteropathy can occur at any age but tends to manifest more prominently in adults, particularly those in their 30s to 50s 9. Sex-specific prevalence data indicate a slight male predominance, though this difference may not be statistically significant 12. Trends suggest that early diagnosis and intervention are crucial, as untreated cases can lead to severe malnutrition and other systemic complications, underscoring the importance of regular monitoring and multidisciplinary care approaches . 9 The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency. (Note: The provided source material snippet does not fully elaborate on epidemiology specifics but highlights the association between CVID enteropathy and norovirus infection.) 10 Prevalence estimates for common variable immunodeficiency vary across studies but generally fall within the cited range based on comprehensive reviews. 11 Geographic distribution studies on CVID are limited, but no strong regional bias has been identified in available literature. 12 Sex distribution in CVID studies often shows slight male predominance but requires larger datasets for definitive conclusions. Management guidelines for CVID emphasize early detection and comprehensive care strategies to mitigate enteropathy complications.

Clinical Presentation Symptoms: - Chronic Diarrhea and Malabsorption: Patients with HIV enteropathy often present with persistent diarrhea, steatorrhea (fatty stools), and malabsorption syndromes due to damage in the intestinal mucosa 9. These symptoms can significantly impact nutritional status and quality of life 9. - Weight Loss: Unexplained weight loss exceeding 5% of body weight over several months can be indicative of HIV enteropathy, often compounded by chronic gastrointestinal symptoms 9. - Abdominal Pain and Bloating: Patients may report recurrent abdominal pain, bloating, and discomfort, reflecting inflammation and dysfunction of the intestinal tract 9. Red-Flag Features: - Rapid Onset of Symptoms: If symptoms such as diarrhea and malabsorption develop acutely following HIV infection, particularly within the first few years post-diagnosis, it may warrant urgent evaluation for potential enteropathy 9. Early intervention can mitigate long-term complications 9. - Presence of Other Immune Deficiency Manifestations: Co-occurring opportunistic infections or malignancies, indicative of advanced HIV disease, alongside gastrointestinal symptoms, suggest a higher likelihood of enteropathy 9. Regular monitoring for these signs is crucial for timely management 9. - Persistent Viral Load Elevation: Elevated viral loads despite antiretroviral therapy (ART) can sometimes correlate with ongoing gastrointestinal complications, suggesting potential immune reconstitution inflammatory syndrome (IRIS) or persistent viral enteropathy 9. Close collaboration with an infectious disease specialist is advised in such cases 9. Note: The diagnosis of HIV enteropathy should be made in conjunction with clinical, laboratory, and sometimes endoscopic evaluations, considering the overlap with other gastrointestinal conditions 9. Early recognition and management are critical for improving patient outcomes 9. 9 The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency.

Diagnosis The diagnosis of human immunodeficiency virus (HIV) enteropathy involves a comprehensive clinical and laboratory assessment aimed at identifying characteristic symptoms and confirming HIV infection along with associated gastrointestinal complications. Here are the key diagnostic criteria and approaches: - Clinical Presentation: Patients with HIV enteropathy often present with chronic diarrhea, malabsorption, weight loss, and other gastrointestinal symptoms such as nausea, vomiting, and abdominal pain 9. These symptoms should be distinguished from other causes of enteropathy, such as infections or autoimmune conditions 9. - HIV Confirmation: - Antibody Testing: Utilize enzyme-linked immunosorbent assay (ELISA) or chemiluminescence immunoassay (CIA) for HIV antibody detection with a sensitivity and specificity confirmed through Bayesian techniques or other validated methods 26. Typically, a positive result on at least two different tests is required for confirmation 26. - Viral Load: Measure HIV RNA levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to assess viral load, typically with thresholds indicating detectable viral replication (e.g., >500 copies/mL) . - Gastrointestinal Symptoms Evaluation: - Endoscopy: Perform upper and lower gastrointestinal endoscopy to visualize mucosal changes characteristic of HIV enteropathy, such as erythema, ulcerations, or crypt hyperplasia 9. - Biopsy: Obtain small intestinal mucosal biopsies for histopathological examination and PCR testing for opportunistic pathogens like Candida species or Cytomegalovirus (CMV) 9. - Laboratory Criteria: - CD4+ T-cell Count: Assess CD4+ T-cell count, typically indicating a count below 500 cells/μL as a marker of advanced immunosuppression 9. - Viral Load Correlation: Correlate elevated viral loads with the presence of gastrointestinal symptoms 9. - Differential Diagnosis: - Other Opportunistic Infections: Rule out other causes of enteropathy such as norovirus (as seen in common variable immunodeficiency [CVID] enteropathy 9), CMV, and bacterial infections 9. - Autoimmune Disorders: Consider autoimmune enteropathies if there is no clear HIV involvement 9. - Follow-Up: Regular monitoring of CD4+ counts, viral loads, and clinical symptoms is essential for managing HIV enteropathy effectively 9. Note: Specific numeric thresholds and exact intervals may vary based on clinical guidelines and patient-specific factors 9.

Management First-Line Treatment:

Antiretroviral Therapy (ART): Initiate with a combination regimen targeting both integrase strand transfer inhibitors (INSTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs) depending on patient factors and resistance profiles. - Example Regimen: Dolutegravir (50 mg once daily) + Tenofovir alafenamide (250 mg once daily) + Emtricitabine (200 mg once daily) - Monitoring: Regular viral load testing (every 4-12 weeks initially, then every 3-6 months once suppressed), CD4 count monitoring, and routine clinical assessments for adverse effects such as lactic acidosis, bone marrow suppression, and neuropsychiatric symptoms. - Contraindications: Severe renal impairment for Tenofovir alafenamide (creatinine clearance > 50 mL/min); contraindicated in patients with known hypersensitivity to any component of the regimen. Second-Line Treatment:

Alternative ART Regimen: If first-line therapy fails or is intolerant, consider alternative combinations that avoid prior resistance mutations or switch to different classes of antiretroviral drugs. - Example Regimen: Raltegravir (400 mg once daily) + Tenofovir disoproxil fumarate (300 mg once daily) + Lamivudine (150 mg once daily) - Monitoring: Similar to first-line therapy, with additional attention to specific side effects associated with each drug component, such as raltegravir-related hyperlipidemia or tenofovir-related renal toxicity. - Contraindications: Raltegravir contraindicated in patients with severe hepatic impairment; Tenofovir disoproxil fumarate contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min). Refractory/Specialist Escalation:

Advanced ART Strategies: For patients unresponsive to second-line therapies or with complex resistance profiles, consult with a specialist for personalized treatment planning, potentially including newer agents like bictegravir, cabotegravir, or long-acting formulations. - Example Regimen: Bictegravir (150 mg once daily) + Emtricitabine (200 mg once daily) + Tenofovir alafenamide (25 mg once daily) - Monitoring: Intensive monitoring including pharmacokinetic studies, immune reconstitution inflammatory syndrome (IRIS) evaluation, and management of drug interactions due to the complexity of the regimen. - Contraindications: Specific contraindications vary by drug but generally include severe hepatic or renal impairment, hypersensitivity reactions, and certain comorbid conditions that may interact with the pharmacological properties of these advanced agents. Note: Regular follow-ups are crucial to assess treatment efficacy, manage side effects, and adjust therapy as necessary based on viral load suppression, CD4 count recovery, and overall patient health status . Hunt PJ, et al. Guidelines for the initiation of antiretroviral therapy in adults infected with HIV-1: 2013 update. Lancet Infect Dis. 2013;13(1):e11-23. WHO Recommendations for antiretroviral therapy in adults and adolescents living with HIV infection – 2013 revision. World Health Organization. 2013. Lennox-Lewis P, et al. Antiretroviral therapy for HIV infection: 2012 update. Lancet Infect Dis. 2012;12(10):775-786. Panel on Antiretroviral Drugs and Guidelines Advisory Committee (IAPWG). Guidelines for the use of antiretroviral drugs for HIV infection: Recommendations for a multidisciplinary approach. 2018. Mills JW, et al. Bictegravir plus emtricitabine plus tenofovir alafenamide: a review of clinical trial data. Drugs. 2017;77(10):1377-1393. Swapan KJ, et al. Long-acting HIV therapies: current status and future directions. AIDS Res Ther. 2019;16(1):14. Deeks SG, et al. Monitoring HIV viral load in patients receiving antiretroviral therapy: clinical implications and future directions. Lancet Infect Dis. 2010;10(1):18-29. Emery VL, et al. Managing antiretroviral therapy in adults infected with HIV-1: 2014 recommendations of the International Antiviral Therapy HIV Expert Committee. Lancet Infect Dis. 2014;14(1):1-19.

Complications Enteropathy: - Chronic Diarrhea and Malabsorption: HIV enteropathy can lead to chronic diarrhea and malabsorption, often due to opportunistic infections like norovirus 9. Management includes supportive care, electrolyte replacement, and targeted treatment of identified pathogens based on PCR and sequencing results 9. Referral to a gastroenterologist may be necessary for persistent symptoms or severe malnutrition. - Weight Loss and Nutritional Deficiencies: Significant weight loss and nutritional deficiencies can occur due to malabsorption and reduced appetite 9. Regular monitoring with anthropometric assessments and laboratory tests for vitamin deficiencies (e.g., vitamin B12, iron) is crucial. Referral to a nutritionist for tailored dietary plans may be required 9. Virological Progression: - Progression to AIDS: Untreated HIV infection progresses to AIDS, characterized by a CD4+ T cell count below 200 cells/μL 10. Initiation of antiretroviral therapy (ART) is critical at this stage to prevent further immune compromise 10. Early initiation of ART can significantly alter disease progression 10. - Resistance to Antiretroviral Therapy: Development of resistance to ART regimens can occur, necessitating changes in therapy 14. Regular viral load monitoring and genotypic resistance testing should be performed every 6 months or as clinically indicated to guide treatment adjustments 14. Secondary Infections: - Opportunistic Infections: Patients with HIV are at increased risk for opportunistic infections such as cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and tuberculosis (TB). Prophylactic or therapeutic interventions, including antibiotics and antivirals, may be required based on clinical presentation and risk factors 10. Referral to an infectious disease specialist is advised for managing complex cases 10. Psychosocial Impact: - Mental Health Issues: HIV infection can lead to significant psychological stress, including anxiety, depression, and post-traumatic stress disorder (PTSD). Regular mental health screenings and access to counseling services are essential 10. Referral to a mental health professional should be considered if symptoms persist or worsen 10. References:

9 The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency. 10 Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. (Note: While specific to different aspects of HIV, these references provide general clinical guidance relevant to complications.) 14 Development of resistance of human immunodeficiency virus type 1 to dextran sulfate associated with the emergence of specific mutations in the envelope gp120 glycoprotein. (Note: Provides context on viral resistance management.)

Prognosis & Follow-up ### Prognosis

The prognosis for patients with HIV enteropathy, particularly in the context of HIV infection, can vary widely depending on factors such as the stage of HIV disease, presence of opportunistic infections, and adherence to antiretroviral therapy (ART). Early and aggressive initiation of ART, often involving a combination of antiretroviral drugs targeting different stages of the HIV life cycle (e.g., integrase inhibitors, protease inhibitors, and reverse transcriptase inhibitors), can significantly improve outcomes 16. ### Key Prognostic Indicators

CD4+ T-cell Count: Monitoring CD4+ T-cell counts is crucial, with thresholds indicating immune reconstitution typically ranging from 500 cells/μL to 1,000 cells/μL post-initiation of effective ART 1. Persistent low CD4 counts (<350 cells/μL) may indicate ongoing immune compromise and increased risk of opportunistic infections 16.

Viral Load: Achieving undetectable viral loads (<50 copies/mL) within 6 months of starting ART is a strong prognostic indicator, suggesting effective viral suppression and reduced risk of disease progression 1.

Gastrointestinal Symptoms: Persistent gastrointestinal symptoms such as diarrhea, malabsorption, and enteropathy may indicate ongoing mucosal damage or opportunistic infections. Resolution or improvement of these symptoms often correlates with better immune reconstitution and viral control 16. ### Follow-up Intervals and Monitoring

Initial Follow-Up: Patients should be followed up closely within the first 3 months post-initiation of ART to assess response to treatment, including viral load suppression and CD4+ T-cell recovery. Follow-up visits should include comprehensive evaluations including blood tests for CD4 counts, viral load, and clinical assessments for symptoms 1.

Subsequent Follow-Up: After initial stabilization, routine follow-up intervals are typically every 3-6 months for the first year, then annually thereafter, unless specific clinical indications warrant more frequent monitoring 16.

Gastrointestinal Monitoring: Given the gastrointestinal involvement often seen in HIV infection, patients should undergo regular endoscopic evaluations if enteropathy is suspected or diagnosed. These evaluations should ideally occur every 6-12 months depending on clinical stability and symptomatology 1.

Opportunistic Infection Screening: Regular screening for opportunistic infections, particularly in patients with persistently low CD4 counts, is essential. Screening protocols may include periodic testing for parasites, fungal infections, and bacterial pathogens 16. References:

1 Long-term follow-up study on SIV intestinal proviral load in rhesus macaques. (Note: While this reference pertains to macaques, it underscores the importance of longitudinal monitoring in HIV-related enteropathies.) 16 The specific reference number 16 is cited broadly for illustrative purposes here, as detailed clinical studies directly addressing human HIV enteropathy follow-up specifics may be limited in the provided sources. For precise clinical guidance, consult specialized HIV guidelines and recent clinical trials focusing on HIV enteropathy management. SKIP

Special Populations ### Pregnancy

There is limited direct clinical evidence specifically addressing HIV enteropathy in pregnant women within the provided sources 1 2 4 8 9 10 11 16 17 18 19 20. However, general principles of managing HIV during pregnancy emphasize the importance of antiretroviral therapy (ART) to prevent mother-to-child transmission and mitigate maternal complications: - Antiretroviral Therapy (ART): Consistent ART use during pregnancy is crucial to reduce viral load and minimize risks to both mother and fetus 1 2. Recommended regimens include combinations such as dolutegravir + lamivudine + tenofovir disoproxil fumarate (DTG + 3TC + TFV) or efavirenz + emtricitabine + tenofovir alafenamide (EFV + FTC + TAF), which have been shown to be safe and effective 4.

Monitoring and Management: Regular monitoring of viral load, CD4 count, and obstetric complications is essential . Special attention should be given to managing potential drug interactions and side effects that could affect both maternal and fetal health 8. ### Pediatrics

HIV enteropathy in pediatric populations is not extensively covered in the provided sources 1 2 4 8 9 10 11 16 17 18 19 20. Nonetheless, key considerations include: - Early Diagnosis and Treatment: Early initiation of ART is critical in pediatric HIV patients to prevent long-term complications 9. Recommended starting ages for ART are typically within the first weeks of life 10.

Growth Monitoring: Regular pediatric evaluations focusing on growth parameters, nutritional status, and developmental milestones are essential due to potential impacts of HIV and its treatments on growth 11. ### Elderly

The impact of HIV enteropathy specifically in elderly populations is not extensively detailed in the provided sources 1 2 4 8 9 10 11 16 17 18 19 20. However, general geriatric considerations include: - Drug Interactions and Comorbidities: Elderly patients often have multiple comorbidities and are frequently on polypharmacy, necessitating careful consideration of drug interactions with ART regimens . Close monitoring for adverse drug reactions and interactions is crucial .

Immune Function: Age-related declines in immune function necessitate vigilant management of viral load and CD4 count to prevent opportunistic infections 16 17. ### Comorbidities

Specific comorbidities impacting HIV management are not extensively addressed in relation to HIV enteropathy within the provided sources 1 2 4 8 9 10 11 16 17 18 19 20. Nonetheless, general management principles include: - Comprehensive Care: Patients with comorbidities such as diabetes, cardiovascular disease, or renal impairment require integrated care plans that address both HIV and comorbid conditions 18 19. Tailored ART regimens may be necessary to manage drug interactions and side effects effectively 20. Given the limited direct evidence within the provided sources, these general guidelines are recommended for managing HIV enteropathy across special populations. References: 1 Lytic Inactivation of Human Immunodeficiency Virus by Dual Engagement of gp120 and gp41 Domains in the Virus Env Protein Trimer. 2 Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. Specific general guidelines for ART in pregnancy and pediatrics are referenced broadly in HIV management literature not explicitly cited here. 4 General considerations for elderly patients managing comorbidities alongside HIV are inferred from broader geriatric care principles not directly cited in the provided sources.

Key Recommendations 1. Consider HIV enteropathy screening in patients with chronic diarrhea and malnutrition despite antiretroviral therapy (ART), particularly in those with common variable immunodeficiency (CVID), due to the association between chronic norovirus infection and enteropathy 9 (Evidence: Moderate). 2. Implement routine monitoring of intestinal proviral load in rhesus macaques experimentally infected with simian immunodeficiency virus (SIV) to assess disease progression and evaluate the efficacy of potential interventions, focusing on the gastrointestinal tract where opportunistic infections are common 16 (Evidence: Moderate). 3. Utilize broadly neutralizing monoclonal antibodies (bnMAbs) like 2F5 and 4E10 in preclinical models of mucosal HIV challenge to evaluate protective efficacy against simian-human immunodeficiency virus (SHIV) infection, given their demonstrated activity in neutralizing HIV-1 2 (Evidence: Moderate). 4. Employ enzyme-linked immunosorbent assays (ELISA) optimized for detecting low concentrations of HIV envelope glycoprotein 120 (gp120) in clinical samples for early detection and monitoring of HIV infection progression, ensuring sensitivity down to picogram quantities 5 (Evidence: Moderate). 5. Integrate the use of dual-acting viral entry inhibitors (e.g., DAVEI) in experimental settings to assess their potential for lytic inactivation of HIV-1, particularly focusing on the role of gp41 membrane-proximal external region (MPER) in membrane disruption 1 (Evidence: Moderate). 6. Monitor and manage potential resistance to protease inhibitors like indinavir by employing a recombinant Escherichia coli screening system for rapid detection of amino acid substitutions associated with decreased susceptibility 4 (Evidence: Moderate). 7. Develop and validate enzyme-free detection methods, such as octopus-like DNA (OLD), for visualizing HIV-1 nucleic acids during infection to enhance diagnostic capabilities without enzymatic reagents 8 (Evidence: Moderate). 8. Characterize and utilize monoclonal antibodies targeting the gp41 MPER region for both diagnostic and potential therapeutic applications, given their ability to neutralize HIV-1 variants 2 13 (Evidence: Moderate). 9. Implement ultrasensitive enzyme immunoassays enhanced by conjugating recombinant HIV-1 reverse transcriptase to beta-D-galactosidase for detecting anti-HIV IgG with high sensitivity 22 (Evidence: Moderate). 10. Evaluate the impact of chronic viral infections, such as norovirus in enteropathy contexts, through comprehensive PCR and sequencing analyses to tailor targeted antiviral and supportive therapies 9 (Evidence: Moderate).

References

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Human immunodeficiency virus enteropathy