The human immunodeficiency virus (HIV) targets the immune system, specifically destroying CD4+ T-cells. Diarrhea is a frequent complication for individuals living with HIV, affecting those who are newly infected, have advanced disease, or are undergoing treatment. This gastrointestinal issue can range from an acute episode to a serious, chronic condition that significantly impacts quality of life and nutritional status. Identifying the specific cause of diarrhea is important because management strategies differ depending on whether the issue stems from the virus itself, an opportunistic infection, or a medication side effect.
Diarrhea as a Symptom of Untreated HIV Infection
In the absence of effective treatment, HIV disease often leads to diarrhea through two primary mechanisms: direct viral damage and secondary opportunistic infections. The virus itself can cause a condition known as HIV enteropathy, where it directly attacks gastrointestinal tract cells and gut-associated lymphoid tissue. This direct damage results in inflammation and structural changes, such as the blunting of the villi, which are responsible for nutrient absorption in the small intestine. The resulting malabsorption leads to chronic, non-infectious diarrhea and can contribute to weight loss.
As the CD4+ T-cell count declines, the weakened immune system becomes vulnerable to pathogens that typically do not cause illness in healthy individuals. These opportunistic infections (OIs) are a major cause of diarrhea. The risk and type of infection are closely tied to the degree of immunosuppression, with a CD4 count below 200 cells/mm³ signaling increased susceptibility.
Protozoan parasites are frequent culprits, including Cryptosporidium, Microsporidia, and Cystoisospora belli, which can cause severe, high-volume, watery diarrhea. Viral infections, such as Cytomegalovirus (CMV), often cause colitis (inflammation of the colon) that can be accompanied by bloody stools and abdominal pain, typically manifesting when the CD4 count drops below 50 cells/mm³. At this advanced stage of immunosuppression, disseminated infections like Mycobacterium Avium Complex (MAC) can also affect the intestines, presenting with diarrhea alongside systemic symptoms like fever and wasting. Treating these specific OIs is mandatory to resolve the associated gastrointestinal symptoms.
Diarrhea Caused by Antiretroviral Therapy (ART)
With the widespread use of antiretroviral therapy (ART), medication side effects have become a significant cause of non-infectious diarrhea. ART-associated diarrhea is related to the pharmacological properties of certain drugs, rather than an infectious agent. This issue is often acute, beginning shortly after a patient starts a new regimen, but it can persist and become chronic, leading to poor adherence to the treatment plan.
Specific classes of ART are known to irritate the gastrointestinal tract, with protease inhibitors (PIs) carrying the greatest risk. Drugs like ritonavir, which is often used as a booster for other PIs, are particularly associated with this side effect. These medications can directly damage the intestinal lining, increasing its permeability in a process known as leaky-flux diarrhea.
Certain antiretrovirals can also interfere with the normal movement of water and electrolytes across the intestinal wall, leading to secretory diarrhea. Some nucleoside reverse-transcriptase inhibitors (NRTIs) are also known to cause gastrointestinal upset, including diarrhea, as a common adverse event. Managing this type of diarrhea often involves adjusting the ART regimen or using specific anti-diarrheal medications designed to counteract the drug’s effects.
Identifying the Underlying Cause
Accurately determining the cause of diarrhea is necessary before effective management can begin, as the source can be infectious, non-infectious, or medication-related. A clinician will begin with a thorough patient history, which includes documenting the duration and character of the diarrhea, the patient’s current ART regimen, and their most recent CD4 count and viral load. This clinical information can provide immediate clues, such as a very low CD4 count pointing toward an opportunistic infection.
Microbiological testing of stool samples is standard to rule out infectious causes. This analysis typically includes cultures for common bacterial pathogens, testing for Clostridium difficile toxin, and microscopic examination for ova and parasites. For patients with advanced immunosuppression, specialized testing for organisms like Cryptosporidium and Microsporidia must be explicitly requested.
If initial stool tests are negative and the diarrhea is chronic, advanced diagnostics may be required to check for conditions like HIV enteropathy or deep-seated infections. A procedure such as a colonoscopy or endoscopy allows the physician to visually inspect the intestinal lining and collect biopsy samples. These tissue samples are then analyzed for inflammation, structural damage, or the presence of specific pathogens like Cytomegalovirus, providing a definitive diagnosis.
Strategies for Managing Chronic Diarrhea
The management of chronic diarrhea involves a multi-pronged approach that targets the root cause while providing symptomatic relief and nutritional support. If an opportunistic infection is identified, the primary strategy is to treat the specific pathogen with targeted antimicrobial or antiviral therapy. For instance, specific parasite infections require dedicated anti-parasitic agents, while CMV colitis is treated with antiviral drugs like ganciclovir.
For diarrhea suspected to be caused by ART, a physician may adjust the medication by either lowering the dose or switching the patient to a different, less gastrotoxic drug regimen. A prescription medication called crofelemer is approved to treat non-infectious diarrhea in people with HIV who are receiving ART. This drug works by regulating fluid secretion in the gut.
Symptomatic and supportive care is a major focus, as diarrhea can lead to dangerous dehydration and malnutrition. Dietary modifications are often recommended, such as avoiding foods high in fat or lactose, which can exacerbate symptoms. Oral rehydration solutions are important to replace lost fluids and electrolytes. Over-the-counter agents like loperamide are commonly used for symptomatic relief, but their use must be approached with caution until an infectious cause like C. difficile has been ruled out.