The Story of CVT in HIV-HBV Co-infection
A young man's seizure uncovers a hidden battle within his veins, where two viruses conspire to create a life-threatening clot.
In the intricate world of medicine, the human body sometimes presents puzzles where one unexpected symptom can point to multiple hidden diseases. This is the story of cerebral venous thrombosis (CVT)—a rare blood clot in the brain's veins—and how it can unexpectedly reveal a co-infection with two notorious viruses: human immunodeficiency virus (HIV) and hepatitis B virus (HBV).
For most, a headache might seem minor, but for clinicians, it can be the critical clue leading to a complex diagnosis of intertwined infections, transforming our understanding of viral effects on the human body.
To appreciate the significance of a CVT diagnosis, one must first understand the key players. HIV and HBV are both major global health challenges, and because they share modes of transmission—such as blood contact, sexual contact, and from mother to child—they often occur together. This is known as co-infection 3 6 .
Ordinarily, viruses like HIV and HBV are associated with immune deficiency or liver inflammation. A blood clot in the brain seems like an unrelated problem. However, research has shown that HIV infection is linked to a two- to tenfold increased risk of venous thromboembolism (blood clots in the veins) compared to the general population 4 .
HBV, while more rarely linked to clots, has been associated with increased platelet activation and other thrombophilic mechanisms 1 . When combined, these viruses can create a perfect storm within the bloodstream, tilting the body's delicate balance toward thrombosis.
The fascinating link between CVT and HIV-HBV co-infection was powerfully illustrated in a landmark case report published in Medical Research Archives 1 . This case provides a real-world example of how this complex condition can present and be managed.
A 25-year-old Indian man was admitted to the emergency room after experiencing a sudden-onset seizure involving the right side of his body. This was preceded by a dull, aching headache that had persisted for two weeks. He had no history of fever, trauma, or other common triggers.
Upon examination, doctors found weakness in his right arm and a facial palsy. General examination revealed tell-tale signs of intravenous drug abuse: healed cut marks and punctuate scars over his forearms 1 . This crucial piece of social history raised immediate red flags for blood-borne infections.
The medical team embarked on a systematic investigation to find the cause of his neurological symptoms:
A computed tomography (CT) scan revealed an intracerebral hematoma (a bleed in the brain tissue). Following this, a magnetic resonance venography (MRV) scan provided the definitive answer: it showed thrombosis in the superior and inferior sagittal sinuses—major veins in the brain 1 .
Doctors ran an extensive battery of blood tests to uncover a predisposition to clotting. Surprisingly, levels of Protein C, Protein S, antithrombin III, homocysteine, and antiphospholipid antibodies were all normal 1 .
With the high-risk behavior of IV drug use, serological tests for infectious diseases were performed. The results were conclusive: the patient was positive for both HIV-1 and hepatitis B surface antigen (HBsAg). Further tests confirmed an acute HBV infection. Notably, his CD4 count was 529 cells/μL, which is within the normal range, and there were no demonstrable opportunistic infections 1 .
Remarkable Finding: CVT was the first and only manifestation of his HIV-HBV co-infection, occurring despite a relatively healthy immune cell count.
| Test | Finding | Significance |
|---|---|---|
| MRV Brain | Superior & Inferior Sagittal Sinus Thrombosis | Confirmed Cerebral Venous Thrombosis (CVT) |
| HIV Serology | Reactive for HIV-1 | Confirmed HIV Infection |
| HBV Serology | HBsAg Positive | Confirmed Hepatitis B Infection |
| CD4 Count | 529 cells/μL | Normal immune cell count, ruling out severe immunodeficiency |
| Thrombophilia Screen | Normal Protein C, S, Antithrombin III, etc. | Ruled out other common genetic or acquired clotting disorders |
The patient was started on a dual-treatment strategy:
He received conventional anticoagulation therapy, beginning with intravenous unfractionated heparin and overlapping with warfarin.
He was started on antiretroviral therapy (ART) with tenofovir, dolutegravir, and lamivudine—a regimen active against both HIV and HBV 1 .
The outcome was positive. His headache disappeared within a week, and the weakness in his arm and face gradually improved. He was discharged on warfarin and strict monitoring for his international normalized ratio (INR), alongside continued antiviral therapy 1 .
The big question remains: what exactly caused the clot? The study authors proposed that the cause was likely multifactorial 1 . It was impossible to pinpoint a single culprit, but the combination of HIV infection, HBV infection, and a history of intravenous drug abuse likely created a synergistic prothrombotic milieu that none of these factors would have achieved alone 1 4 .
The normal thrombophilia workup suggests the viruses themselves directly or indirectly disrupt the clotting balance in ways not yet fully understood.
The management of HIV-HBV co-infection has evolved significantly. The current standard of care involves antiretroviral regimens that are active against both viruses. The most common of these are tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) in combination with emtricitabine or lamivudine 3 8 .
Recent clinical trials, such as the ALLIANCE Phase III study, have shown that modern regimens like Biktarvy (a TAF-based single-tablet regimen) demonstrate long-term efficacy and safety in co-infected patients. After three years of treatment, this regimen achieved 99% suppression of HIV-1 and 80.2% suppression of HBV DNA, showcasing the powerful tools now available to clinicians 8 .
| Drug | Function | Role in Co-infection |
|---|---|---|
| Tenofovir (TDF/TAF) | Nucleos(t)ide Reverse Transcriptase Inhibitor (NRTI) | Potently suppresses HBV replication and is a backbone of HIV therapy. A high barrier to HBV resistance. |
| Emtricitabine (FTC) | Nucleoside Reverse Transcriptase Inhibitor (NRTI) | Suppresses both HIV and HBV. Almost always used in combination with tenofovir. |
| Lamivudine (3TC) | Nucleoside Reverse Transcriptase Inhibitor (NRTI) | Suppresses both viruses, but HBV resistance to lamivudine develops easily, so it is no longer preferred as the sole anti-HBV agent. |
Essential for managing co-infection:
The case of the 25-year-old man is more than a successful treatment story; it is a powerful lesson in clinical vigilance. It underscores that CVT can be the sole presenting manifestation of HIV-HBV co-infection, even in individuals with a normal CD4 count and no other signs of illness 1 .
Clinical Recommendation: This finding argues strongly for routine serologic testing for HIV and HBV in any patient presenting with CVT who has known high-risk behaviors 1 . Such testing can unlock the root cause of the thrombotic event and ensure that patients receive the comprehensive, dual-targeted therapy they need.
As research continues to shed light on the complex interactions between these viruses and the human vascular system, the medical community's ability to diagnose, treat, and ultimately improve outcomes for patients with such challenging co-infections will only grow stronger.
Key areas for future investigation include: