Keywords
HIV, AIDS, HIV and anesthesia, HIV and intensive care
Case Synopsis
A 34-year-old woman with known human immunodeficiency virus (HIV) infection and a recent diagnosis of acquired immunodeficiency syndrome (AIDS) with Pneumocystis jirovecii (previously carinii ) pneumonia presents for elective cesarean section at 38 weeks’ gestation. She has not been followed by health care clinicians during her pregnancy and has not been taking antiretroviral therapy. She is very short of breath and has a dry cough, and her peripheral arterial oxygen saturation is 84% on room air. She weighs 62 kg, and her height is 164 cm. Her tympanic temperature is 37.2° C. She is alert and oriented, with no localizing neurologic signs. Her blood pressure is 90/50 mm Hg; her heart rate is 115 beats per minute, with no respiratory variation; and her respiratory rate is 26 breaths per minute. Recent laboratory tests show a CD4 T-cell count of 186 cells/mL and an HIV viral load of 240,000 copies/mL.
Problem Analysis
Definition
AIDS was first described in 1981 in the United States. HIV and, despite major therapeutic advances in recent years, the AIDS pandemic still pose a major threat to global health. It is estimated that more than 40 million people worldwide are infected with HIV, which is thought to have caused more than 20 million deaths to date. The infection continues to spread apace, with the most rapid increases observed in southern and central Africa and in South Asia. The predominant mode of HIV transmission is heterosexual sex, and women represent a high proportion of new infections, including in developed countries.
Increasing numbers of patients presenting for surgery are HIV-seropositive or have AIDS. Anesthesiologists should be familiar with this disease and be aware of the impact of HIV on anesthesia. An understanding of the pathogenesis of HIV and an awareness of the possible drug interactions occurring with HIV therapy may help guide the choice of anesthetic technique. The possibility of nosocomial transmission of HIV highlights the need for anesthesiologists to enforce rigorous infection control policies to protect themselves, other health care workers, and their patients. Antiretroviral therapy decreases the rate of disease progression, but there is no cure available, nor is a vaccine likely in the foreseeable future. With marked advances in treatment, the emphasis has shifted to early initiation of multidrug therapy regardless of immune status, and ongoing treatment to achieve HIV viral suppression throughout life.
Recognition
HIV belongs to the family Retroviridae and the genus Lentivirus. Members of this genus are cytopathic (cell damaging), have long latent periods, and run a chronic course. When cases of AIDS first appeared, its pathogenesis was frustratingly elusive because the disease does not appear immediately on infection with HIV. There is a variable period during which the patient remains healthy but is viremic.
Acute seroconversion illness occurs with a high viral load soon after infection. After several months, there is a gradual decrease in the viremia as the immune response occurs. The viral load is often at a steady state as the rate of viral production equals the rate of destruction. Up to 98% of T-helper lymphocytes (CD4 T cells) are located in lymph nodes, which are the major site of viral replication and T-cell destruction. There is a gradual involution of the lymph nodes, with a concomitant decrease in CD4 T cells and an increase in viral load as the inexorable onset of AIDS occurs ( Fig. 9.1 ).
Before 1995, prospects for the treatment of HIV were gloomy. Subsequently, the situation changed dramatically as a result of four factors:
- 1.
Improved understanding of the pathogenesis of HIV infection
- 2.
Availability of surrogate markers of immune function and plasma viral burden
- 3.
Development of new and more powerful drugs, such as the protease inhibitors and nonnucleoside reverse transcriptase inhibitors
- 4.
Completion of several large clinical end-point trials that conclusively demonstrated that antiretroviral combinations significantly delayed the progression of HIV disease to AIDS and improved survival
In more recent years, advances have further transformed the treatment of HIV with more drugs, fewer side effects, less toxicity, and less pill burden. It has also been established that early initiation of therapy, regardless of the host’s CD4 T-cell count, renders the virus virtually undetectable, restores immune function, improves quality of life, prevents transmission, reduces HIV-associated morbidity, and lengthens survival. HIV has thus been rendered a less debilitating and ominous infection. Indeed there are real prospects for arresting the pandemic and potentially even eradicating HIV as a major infectious disease threat.
Risk Assessment
HIV is a virus found mainly in CD4 T cells, macrophages, and monocytes, and it requires a large infecting dose for transmission. HIV has been isolated from blood, cerebrospinal fluid, tears, saliva, semen, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid, vaginal secretions, and breast milk. Modes of transmission are through oral, rectal, and vaginal sexual intercourse, blood product transfusion, shared intravenous needles, occupational acquisition, and vertical transmission from mother to child. The screening of blood products for HIV antibodies has reduced the risk of transfusion-associated infection (less than 1 per 750,000 donor units); the exact risk is difficult to quantify, however. Antibody screening fails to detect the virus in the so-called window period before antibody formation, which lasts about 3 months. Nuclear amplification is an alternative technique that has been adopted and allows for early virus detection.
Implications
Universal Precautions
Universal precautions for the prevention of transmission of blood-borne viruses were recommended in 1987 by the Centers for Disease Control. These precautions advise that every patient be regarded as potentially infected with a blood-borne virus.
Postexposure Prophylaxis
Following accidental exposure to a high-risk body fluid, such as a (hollow) needle-stick injury, postexposure prophylaxis (PEP) is recommended for health care workers. This should commence as soon as possible after the injury, ideally within 1 to 2 hours, but it can be considered up to 1 to 2 weeks after the injury. Very-high-risk exposures may be treated beyond this time with a view to modifying rather than preventing infection. A typical postexposure prophylaxis regimen of 4 weeks’ duration is tenofovir plus emtricitabine/lamivudine plus raltegravir/dolutegravir. Such a regimen is excellent for PEP because of excellent tolerability, proven potency in HIV infection, and ease of administration.
Management
Antiretroviral Drug Therapy
Six major classes of antiretroviral agents are currently in use ( Table 9.1 ):
- 1.
Nucleoside analog reverse transcriptase inhibitors (NRTIs, approved in 1987) bind to the evolving viral DNA and prevent the completion of reverse transcription.
- 2.
Protease inhibitors (PIs, 1996) inhibit the HIV protease, which cleaves the polyprotein precursors that ultimately make up the core proteins of the mature virions. PIs bind specifically to the active cleavage site.
- 3.
Nonnucleoside reverse transcriptase inhibitors (NNRTIs, 1998) interfere with the transcriptional activity of reverse transcriptase by binding to it directly, downstream of the active catalytic site.
- 4.
The fusion inhibitor (2003) enfuvirtide interferes binds to the first heptad-repeat (HR1) in the viral envelope glycoprotein gp41 and prevents conformational changes necessary for the fusion of the viral and human CD4 T lymphocyte cellular membrane.
- 5.
The CCR5 antagonist (2007) maraviroc binds to human CCR5 receptor on the cell membrane of the CD4 T lymphocyte, thus blocking the interaction of the HIV gp120 and the CCR5 receptor, but only for CCR5-tropic HIV. It does not block viral entry of CXCR4 tropic HIV, and therefore it is necessary to determine that the infecting HIV strain is CCR5-topic before using this agent.
- 6.
Integrase (strand transfer) inhibitors (INSTIs, 2007) block the integrase enzyme from catalyzing the formation of covalent bonds between the host and viral DNA, which prevents the incorporation of viral DNA into the host chromosome.
| Drug Name | Dosing | Common Side Effects |
|---|---|---|
| Nucleoside Analog Reverse Transcriptase Inhibitors | ||
| Zidovudine (AZT/ZDV) | Oral/IV (twice daily) | Marked toxicity, bone marrow suppression (neutropenia), GI upset, headache |
| Didanosine (DDI) | Oral | Peripheral neuropathy, pancreatitis, diarrhea |
| Zalcitabine (DDC) | Oral | Peripheral neuropathy, pancreatitis, oral ulcers |
| Stavudine (D4T) | Oral | Peripheral neuropathy |
| Lamivudine (3TC) | Oral | Anemia, GI upset |
| Abacavir | Oral | GI upset, potentially fatal acute hypersensitivity (associated with the presence of the HLA-B∗5701) |
| Tenofovir | Oral (once daily) | Renal dysfunction, osteomalacia |
| Emtricitabine | Oral | Headache, GI symptoms |
| Nonnucleoside Analog Reverse Transcriptase Inhibitors | ||
| Nevirapine | Oral | Rash, hepatitis, increased liver enzymes |
| Delavirdine | Oral | Rash, increased liver enzymes |
| Efavirenz | Oral (once daily on empty stomach) | Dizziness, rash, dysphoria, increased liver enzymes, psychotic disturbances |
| Rilpivirine | Oral (once daily with food) | Rash, hepatitis |
| Protease Inhibitors | ||
| Saquinavir | Oral | Diarrhea, raised transaminases, hyperlipidemia, cytochrome P-450 inhibition, arrhythmias |
| Indinavir | Oral + ≥1.5 L H 2 O/24 hr | Nephrolithiasis, hyperbilirubinemia, hyperlipidemia, lipodystrophy, cytochrome P-450 inhibition |
| Ritonavir | Oral | GI upset, circumoral paresthesia, hyperlipidemia, lipodystrophy, cytochrome P-450 inhibition |
| Nelfinavir | Oral | Diarrhea, hyperlipidemia, lipodystrophy, cytochrome P-450 inhibition |
| Atazanavir | Oral (requires acidic pH for absorption) | Dyslipidemia, insulin resistance, hyperglycemia, lipodystrophy, cytochrome P-450 inhibition, P-R interval prolongation |
| Darunavir | Oral (with food and boosted by ritonavir) | Dyslipidemia, insulin resistance, hyperglycemia, lipodystrophy, cytochrome P-450 inhibition, GI symptoms, hepatotoxicity |
| Fosamprenavir | Oral (boosted by ritonavir) | Dyslipidemia, insulin resistance, hyperglycemia, lipodystrophy, cytochrome P-450 inhibition, rash, GI symptoms |
| Lopinavir | Oral (once daily coformulated with ritonavir) | Dyslipidemia, insulin resistance, hyperglycemia, lipodystrophy, cytochrome P-450 inhibition, GI symptoms, arrhythmias, hepatotoxicity |
| Tipranavir | Oral (high pill burden and requires ritonavir boost) | Dyslipidemia, insulin resistance, hyperglycemia, lipodystrophy, cytochrome P-450 inhibition, p-glycoprotein induction, hepatotoxicity, rash, GI symptoms |
| CCR5 Antagonist | ||
| Maraviroc | Oral (twice daily) | Hepatotoxicity, upper respiratory tract infections, fever, orthostatic hypotension |
| Fusion Inhibitor | ||
| Enfuvirtide | Injectable (subcutaneous twice daily) | Pain, erythema, induration, nodules, ecchymoses, hypersensitivity |
| Integrase Inhibitors | ||
| Raltegravir | Oral (twice daily) | Headache, nausea, fatigue, rhabdomyolysis, myopathy |
| Elvitegravir | Oral (improved with food) | Only INSTI metabolized by CYP3A4 system, many drug interactions |
| Dolutegravir | Oral (once daily) | Headache, insomnia |
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