Human immunodeficiency virus infection

Introduction

The burden of human immunodeficiency virus (HIV) infection remains a global public health issue, with an estimated 1.8 million new infections and almost 800,000 acquired immunodeficiency syndrome (AIDS)–related deaths in 2018. Around 38 million people are currently living with HIV worldwide (including 8 million patients not aware of their seropositive status), corresponding to a ∼50% increase over the past two decades that reflects both the continuous dissemination of the virus and a striking improvement of life expectancy in patients with sustained viral replication under combination antiretroviral therapies (cARTs). Indeed, since their advent in 1996, dramatic progresses in the efficacy and safety of cART schemes have converted HIV infection from a rapidly fatal disease to a chronic condition requiring long-term care. Though access to cART remains a major challenge in low-income countries and certain sociologic clusters in middle- and high-income regions, roughly two-thirds of the global seropositive population are now receiving these drugs. This proportion is growing steadily, which translates into a continuous decrease in the incidence of opportunistic infections (OIs) and other AIDS-related events compared with the early years of the HIV pandemic. ^, Meanwhile, lifelong residual viral replication and/or cART-related toxicities may result in HIV-associated non-AIDS (HANA) conditions, especially chronic obstructive pulmonary disease (COPD), atherosclerosis, renal dysfunction, certain neoplasms, and liver diseases.

HIV-infected patients are at high risk for critical illness because of the occurrence of severe OI in those with advanced immunosuppression, a marked susceptibility to bacterial sepsis and tuberculosis at every stage of HIV infection, and a rising prevalence of HANA conditions in patients aging under cART. Along with a steady decline in AIDS-related admissions and an opposite trend in those for exacerbated comorbidities, several patterns of intensive care have changed in this population over the late cART era, notably the emergence of new mechanisms of immunosuppression not directly resulting from AIDS (e.g., antineoplastic chemotherapy or solid organ transplantation [SOT]), the management of cART at the acute phase of critical illness, and a dramatic enhancement in short-term survival that mainly ensues from general advances in ICU practices. ^,

Here, we seek to provide a comprehensive overview of intensive care in HIV-infected patients, including current epidemiologic features, reasons for intensive care unit (ICU) admission, use of life-sustaining therapies, and determinants of short-term outcome. We also summarize the available evidence regarding the management of cART in the ICU, with a focus on severe adverse events, administration issues, and timing of initiation in patients admitted for AIDS-related OI.

The continuum of HIV infection: Impact on clinical presentation at ICU admission

Convergence of clinical presentation and outcomes in critically ill HIV-infected and seronegative patients

As a result of easier access to cART and sequential improvements in intensive care practices, critically ill HIV-infected individuals now share several similarities with the general population of ICU patients. First, the reasons for ICU admission are evenly distributed between seropositive and HIV-uninfected patients, with acute respiratory failure (ARF, 40%–60% of all admissions), bacterial sepsis (10%–20%, mostly resulting from respiratory, intraabdominal, and bloodstream infections), and impaired consciousness (10%–20%) being the main clinical vignettes in both subgroups. ^{, , ,} Admissions for acute kidney injury (AKI), gastrointestinal bleeding, acute-on-chronic liver failure, or scheduled postoperative management become more regular over time, which merely reflects the increasing prevalence of at-risk comorbidities in HIV-infected individuals—for instance, HIV/HCV-coinfected patients are more prone to developing AKI.

More than two-thirds of current admissions are not directly related to AIDS, ^, a proportion that is expected to amplify in the years to come. For a given reason of ICU admission, the etiologic spectrum is increasingly analogous to what is observed in HIV-uninfected subjects. Indeed, bacterial pneumonia, COPD exacerbation, complicated lung cancer, and pulmonary edema caused by congestive heart failure have become major causes of ARF, and stroke or Streptococcus pneumoniae meningitis are overtaking classic OIs of the central nervous system (CNS) in patients admitted for life-threatening neurologic disorders. ^, Again, chronic HIV infection stands out as an independent risk factor for most of these AIDS-unrelated conditions.

Notwithstanding a manifest propensity to these diseases, the clinical presentation of common community-acquired infections does not differ between HIV-infected patients with mild-to-moderate immunosuppression and their seronegative counterparts. This is notably shown for pneumonia caused by S. pneumoniae and Legionella pneumophila, ^, severe COVID-19, ^, or bacterial meningitis. Excepting those with profound immune deficiency, ^, HIV-infected patients with sepsis exhibit no discrepancies in terms of plasma levels of host response biomarkers, disease severity, and survival when compared with HIV-uninfected controls. ^, Therefore the diagnostic workflow and initial management of HIV-infected patients with a protective CD4 cell count for usual OIs (i.e., above 200–250/μL) has no relevant particularities and should follow standard procedures and guidelines.

The spectacular improvement of life expectancy in cART-treated patients offers long-term perspectives that justify maximizing the level of supportive care when indicated. Invasive mechanical ventilation (MV, 40%–50% of all admissions), vasopressors (15%–30%), and renal replacement therapy for AKI (8%–15%) are now used as frequently in seropositive individuals as in the general ICU population (see Table 120.1 ), ^{, , , , ,} with comparable prognoses, including in patients at high risk of death, such as those admitted after cardiac arrest or with acute respiratory distress syndrome (ARDS). ^, Last-resort venovenous or venoarterial extracorporeal membrane oxygenation can be discussed in selected patients, with promising results in available reports. ^,

Strikingly, overall in-hospital mortality rates have fallen from more than 80% in the early 1980s to 20%–40% in the most recent Western cohorts, a shift that likely reflects general improvement in intensive care such as direct admission from the emergency department, prompt antibiotic initiation and hemodynamic interventions in patients with sepsis, or protective MV settings for ARDS. ^, , Short-term outcomes of critically ill HIV-infected patients tend to equal those of seronegative subjects with similar demographics, chronic health status, and underlying diseases (e.g., HCV or malignancy), reason for admission, and extent of organ dysfunction. CD4 cell count, HIV viral load, prior cART use, and an admission for an AIDS-related event (versus other diagnoses) are no longer associated with hospital survival. ^{, ,}

Diagnostic workflow and therapeutic approaches in critically ill HIV-infected patients

In HIV-positive patients, the CD4 cell count, which is the most readily available surrogate marker of immune deficiency, is essential to guide the etiologic work-up, notably in patients with ARF or neurologic disorders ( Fig. 120.1 ). ^{, ,} Except tuberculosis, severe OIs occur almost exclusively in patients with CD4 cells below 200/μL. Some rare conditions, such as severe CMV infection or invasive aspergillosis, may occur at counts below 50/μL. Because a transient drop in CD4 cells is usual at the acute phase of sepsis, diagnostic algorithms should be based on a recent steady-state count, when available, rather than on the count measured at admission. Other baseline features to consider include a prior history of OI at risk for recurrence (e.g., tuberculosis), a geographic origin that predisposes to specific imported OIs (e.g., histoplasmosis), adherence to cART and anti-PCP prophylaxis when prescribed, and comorbidities.