Shingles in HIV: Outcome and discovery

Abstract

Background: Herpes zoster (HZ) is a frequent manifestation in people living with HIV (PLHIV), with a significantly higher incidence compared to the general population. It often presents as an early indicator of immunosuppression, making timely diagnosis and treatment crucial. Methods: This retrospective study, conducted from January 2015 to September 2024, analyzed 45 PLHIV diagnosed with HZ. Patients were recruited from the Infectious Diseases Department (for HIV-related HZ cases) and the Dermatology Department (for complicated HZ cases requiring hospitalization). Clinical and demographic data were collected, including ART status, HZ presentation, and treatment outcomes. Results: The mean patient age was 36.35 years, with a male predominance (M/F ratio: 8). Among the cohort, 12 patients had undiagnosed HIV, and HZ was the presenting symptom that led to HIV diagnosis. The thoracic metameric variant was the most common, with erythematous-vesicular, necrotic-hemorrhagic, and bullous forms observed. 21 patients were on antiretroviral therapy (ART), six of whom developed HZ shortly after ART initiation. Treatment involved oral or intravenous acyclovir, with hospitalization required for complicated or multi-metameric forms and high-risk patients. Outpatient management with close monitoring was provided for stable cases. Conclusions: HZ remains a significant opportunistic infection in PLHIV, often serving as a sentinel sign of undiagnosed HIV. Early HIV screening in patients presenting with HZ and timely initiation of antiviral therapy are essential for improved outcomes. Enhanced awareness and integrated HIV-HZ management strategies are crucial in clinical practice.

Keywords

Herpes zoster screening HIV immunodeficiency

Introduction

Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV).¹ The incidence of HZ is higher in people living with HIV (PLHIV) than in the general population. However, the rate of HZ in PLHIV receiving antiretroviral therapy (ART) remains uncertain.² Herpes zoster is one of the most common cutaneous conditions associated with HIV infection,³ indicating a weakened immune system, and as such should prompt consideration for HIV testing.³

Materials and methods

This retrospective study analyzes 45 cases of herpes zoster (HZ) in people living with HIV (PLHIV) from January 2015 to September 2024. The objective is to assess the occurrence of HZ in PLHIV, including 12 cases that led to an initial HIV diagnosis and those occurring under antiretroviral therapy (ART).

Patients were recruited through two main pathways:

- Infectious Diseases Department: Patients developed HZ during their follow-up, including cases occurring after the initiation of ART. Retrospective cases identified through others that reported herpes zoster episodes prior to their HIV diagnosis, confirmed through photographs they had taken at the time of the outbreak.

- Dermatology Department: Patients hospitalized for complicated forms of herpes zoster or ophthalmic zoster, later found to be HIV-positive, including:

• Multimetameric zoster (involving multiple dermatomes).

• Cephalic/ophthalmic zoster, requiring specialized care.

• Necrotic or hemorrhagic forms, indicating severe immune suppression.

Data collection & analysis

- Demographic data, clinical presentation were recorded.

- Testing for HIV and CD4+ T-cell counts at the time of HZ onset were analyzed.

- Clinical forms of HZ were classified into erythematous-vesicular, necrotic-hemorrhagic, and bullous presentations.

- Complications, including secondary infections, ocular involvement, and treatment-related adverse effects, were assessed.

Results

The mean age of the patients was 36.35 years, with a male predominance (sex ratio M/F 8). Homosexual and bisexual behavior was reported in 61% of patients, and 90% reported unprotected intercourse. A total of 45 patients were included in the study. Among them, 21 were receiving ART, and during the course of their HIV infection, they developed herpes zoster while on treatment. Specifically, six patients experienced HZ within the first months following ART initiation, placing them in the category of immune reconstitution inflammatory syndrome (IRIS). Additionally, 12 patients reported a history of herpes zoster shortly before undergoing HIV testing; they were already HIV-positive but unaware of their status. Their diagnosis was established retrospectively based on patient interviews and photographic documentation. Lastly, in another 12 patients, the onset of herpes zoster was the primary reason for HIV screening at the dermatology department.

Among the 21 patients under ART, five had a CD4 count of less than 200 at the time of HZ onset, and four had counts above 200. The rest were not regularly tested.

Among the six patients who developed herpes zoster after initiating ART, all of them had a baseline CD4 count below 50/mm³ before starting treatment. The time interval between ART initiation and the onset of HZ episodes ranged from 2 weeks to 14 weeks, with an average delay of approximately 7 weeks.

Prodromes included tingling, pain, electric shocks, and pruritus.

Three clinical forms of herpes zoster were identified: erythematous-vesicular (23 cases), necrotic-hemorrhagic (11 cases), and bullous (Figure 1) (11 cases). The thoracic form was most common (15 patients), followed by cervical/cephalic forms (8 patients), and lumbosacral forms (7 patients). Seven patients had multi-metameric forms. Zoster eruptions occurred primarily in spring and fall.

Figure 1.

Bullous Herpes zoster.

Only 18% of Complications were noted, including five cases of local superinfection out of 45 (5/45), three ocular complications (3 out of 45), and one case of kidney dysfunction due to acyclovir (1/45). All patients improved with local treatment and acyclovir therapy; ambulatory or injectable, depending on their condition. Hospitalization was required for complicated or elderly, multi-morbid patients, while those in good general health received outpatient treatment with close monitoring.

Discussion

Human immunodeficiency virus (HIV) is a retrovirus that has a devastating impact on patients’ lives world-wide.⁴ HIV-related dermatoses are highly prevalent. While some skin conditions are uniquely linked to HIV, most are common dermatological disorders that tend to present with increased severity and resistance to treatment. The spectrum of cutaneous manifestations includes those associated with primary HIV infection as well as opportunistic and inflammatory conditions.⁵

Advancements in the field of antiretroviral therapy have effectively transformed HIV infection from a terminal diagnosis to a chronic and manageable condition. The efficacy of this intervention is contingent upon the timely identification of PLHIV. Early identification of HIV results in the initiation of appropriate therapy, which has been shown to reduce the occurrence of opportunistic infections and minimize the risk of viral transmission to patients’ partners and contacts.³

In PLHIV, HZ indicates immune dysfunction, placing the patient in stage B according to the 1993 CDC Atlanta classification.¹ This should prompt HIV testing, even for patients without traditional risk factors.³ Public Health England (PHE) recommends annual HIV testing for at-risk individuals, such as homosexual and bisexual individuals, and every 3 months for those with unprotected sex with new or casual partners.⁴

Various studies on missed opportunities to diagnose HIV infection show that shingles could have enabled early diagnosis in a significant proportion of patients. The fact that herpes zoster is so common, and occurs in young people, should justify the use of an HIV test for early diagnosis.⁶ Herpes zoster is frequently linked to missed HIV testing, with an average delay of 7.8 months in diagnosis.⁴

In a study of HIV-infected American homosexual men, it was found that the severity of herpes zoster, the intensity of pain, and lesions affecting cranial nerves and cervical dermatomes were linked to poor outcomes in HIV-related illness. In our study, we also noted the severity of herpes zoster pain, as well as the cervical and cranial locations, along with a necrotic-hemorrhagic presentation.⁷

Before ART, the incidence of HZ in PLHIV was 10–30 times higher than in HIV-negative individuals. ART has reduced this risk but it remains three times higher than in the general population. Several studies have shown an increase in HZ incidence in the first months of ART initiation, suggesting immune reconstitution inflammatory syndrome (IRIS) may contribute to HZ,¹ a pattern also observed in six of our patients Table 1.

Table 1.

Characteristics of patients with herpes zoster due to immune reconstitution inflammatory syndrome (IRIS) following ART initiation.

Patient	Sexe	Age	HAART start date	Time interval from ART start to HZ episode	CD4 % before HAART	CD4 % closest to HZ episode after HAART
Patient 1	M	24	09-2020	8 weeks	30	—
Patient 2	M	40	10-2021	12 weeks	9	—
Patient 3	M	27	11-2023	2 weeks	49	629 (after 3 months)
Patient 4	M	38	04-2023	8 weeks	3	—
Patient 5	M	27	02-2024	14 weeks	18	—
Patient 6	M	35	06-2024	2 weeks	—	380 (after 1 month)

The absence of standardized definitions for IRIS complicates cross-study comparisons.¹ In our cohort, the onset of HZ following ART initiation ranged from 2 to 14 weeks, with an average delay of approximately 7 weeks. This variability in timing aligns with previous observations that IRIS-related complications tend to emerge within the first few months of ART initiation, as immune restoration triggers an inflammatory response against latent infections Most infectious dermatoses were observed in patients with a CD4 count below 500 cells/mm³.⁸

Most research shows low CD4 counts as the strongest predictor of HZ, although even in patients with higher CD4 levels, HIV infection remains a significant risk factor.¹ Our findings support the hypothesis that severe immunosuppression predisposes patients to immune reconstitution inflammatory syndrome (IRIS)-related herpes zoster.

The risk of herpes zoster is significantly higher in the 15–44 age group among PLHIV, where it is six times greater,¹ which was consistent with our results.

Additionally, children with HIV face a 7 to 20 times greater risk of developing zoster compared to children with leukemia.⁹ Our study included a 10-year-old child, highlighting the importance of recognizing this risk in younger PLHIV (Figure 2).

Figure 2.

Herpes Zoster in ten-year-old child.

In PLHIV, zoster can manifest as unidermatomal, multidermatomal, disseminated, or chronic forms.⁹ Complications are also more common in these patients¹⁰; however, our study did not show this, likely due to prompt treatment, which reduces postherpetic neuralgia by 50%.¹¹ Early intervention remains essential. And the use of herpes zoster vaccine may be considered in PLHIV to prevent herpes zoster and its related complications, which was not used in out context.¹⁰

Given the strong link between certain skin conditions and HIV infection, studies found that screening should be considered when the following are present in case of atypical herpes zoster presentations or Herpes zoster ophthalmicus.⁸

Based on our experience and findings, we propose several key insights; Firstly, we emphasize the importance of systematic HIV testing in young patients presenting with HZ, particularly in the absence of known immunosuppressive conditions. Screening is especially warranted in cases of ophthalmic involvement, necrotic complications, or extensive multi-dermatomal HZ.

The HIV Indicator Diseases Across Europe (HIDE) study reinforces this recommendation, highlighting that opportunistic infections such as HZ represent a crucial opportunity for early HIV detection, especially in patients without other apparent risk factors. Implementing systematic HIV screening in such cases can facilitate earlier diagnosis and treatment initiation, ultimately improving patient outcomes.¹²

Conclusion

Cutaneous diseases continue to be an important aspect of HIV infections. The introduction of antiretroviral therapy has led to improved immune status and a change in the spectrum of presentations.⁵

HZ in PLHIV can serve as an indicator of underlying HIV infection, prompting HIV testing. However, ART may temporarily increase the risk of HZ during the first 6 months of treatment.¹ Providers should be aware that VZV reactivation can also signal immune reconstitution inflammatory syndrome following ART initiation.¹³

Furthermore, early initiation of HZ treatment is crucial to prevent complications, including post-herpetic neuralgia. Finally, vigilance is needed during the initial months of ART, as patients are at increased risk of HZ due to IRIS.

These insights drawn from our study highlight the critical need for early detection and timely management of HZ in PLHIV to improve patient outcomes.

Footnotes

Acknowledgements

I would like to express my sincere gratitude to the patients who participated in this study and to the medical teams for their valuable collaboration. I am also thankful to my colleagues for their scientific contributions and support throughout this work. Special thanks to my professors for their expertise and technical assistance.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Mouna Guechchati

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