IDDT Journal

Discussion

The HLA-B*57:01 allele prevalence in our population was 1.7%. This allele prevalence has been widely studied across various geographic regions, races, and ethnicities. In a study among Northeastern Brazilian HIV-infected patients, the frequency of HLA-B*5701 carriers was 3.1% [16]. Similarly, the prevalence reached 3.4% in a United States-based study [17].

In Europe, the overall estimated prevalence of the allele is higher than in the Americas, reaching 4.98%, which varies by region and country [18]. The frequency is lowest in Romania, at 1.4%, and highest in the Republic of Ireland, at 11.2%. Other countries with significant frequency include southern France at 6.9%, Northern Ireland at 7.5%, the UK at 4.55%, and the European part of Russia at 4.04% [1,13,18]. Additionally, HLA-B*57:01 allele prevalence among HIV-infected patients in Serbia was 8% [21].

In another study from Iran, the prevalence of the HLA-B*5701 allele among the Iranian patient population was 3.0% [15], comparable to the numbers from the Americas.

However, in the Eastern parts of Asia, the prevalenceis much lower, particularly in Chinese Asians compared to non-Chinese Asians. A study from Hong Kong revealed that the prevalence of the HLA-B*57:01 allele was 0.5% among Han Chinese and 1% among non-Chinese Asians [23]. H. Zhang et al. confirmed the low prevalence of the allele among Chinese at 0.86% [24]. Nonetheless, in a study on HIV-infected children in Thailand and Cambodia, the prevalence of the HLA-B*57:01 allele was much higher than that of the Chinese. The allele prevalence was 3.4% in Cambodian children and 4.9% in Thai children [25].

The lowest recorded prevalence of the allele was in Africa, with a 0.1% prevalence across Central and Western African countries [26].

When stratifying for ethnicity, our study found that the HLA allele carrier was more prevalent among Arab patients (92.6%) than nonArab patients (7.4%). The lower prevalence among non-Arabs could be attributed to their lower representation in our cohort. A study in the US reported that HLA-B*57:01 positivity was more prevalent in white individuals (85%) than African American individuals (15%) [17]. Another study in the UK reported a prevalence of 7.93% among Caucasianubjects and 0.26% among (see the previous comment) subjects [19]. Additionally, a Colombia study reported that the allele’s prevalence was 4% for white individuals, 2.6% for individuals of mixed races (primarily mestizo), and 1.9% for Afro-Colombians [22].

Before initiating therapy containing ABC, international guidelines recommend testing for the existence of the HLA-B*57:01 allele to identify patients at risk of developing HSR [12,13]. White and Black HIV-positive US patients hypersensitive to ABC have been linked to the presence of the HLA-B*5701 allele [27].

In our population, among HLA-negative patients, the rate of HSR with ABC administration was 0.5%. Similarly, a study reported that testing for HLA-B*57:01 allele and enrolling exclusively HLAB*57:01-negative subjects to receive ABC resulted in a suspected ABC HSR incidence of 0.5% [17]. There are very few reports in the literature of suspected ABC HSR in patients who test negative for HLA-B*57:01. The rare occurrence of ABC HSR in allelenegative individuals reflects the possibility of other immunologic risk factors not yet identified.

The diagnosis of ABC HSR is based on clinical symptoms [5,6]. It is important to note that a possible diagnosis can still be made even if other alternative diagnoses are plausible. Suppose the only symptom is a rash without other systemic signs including fever, respiratory or gastrointestinal symptoms, malaise, or myalgias. In that case, the patient is unlikely to have an underlying ABC HSR. However, if a patient develops a rash after starting ABC, monitoring them closely for the onset of systemic symptoms is recommended. On the other hand, because symptoms are nonspecific and can involve different organ systems, ABC HSR may be missed and patients misdiagnosed, which would lead to severe adverse reactions and possibly death [6]. Suspected ABC HSR requires immediate discontinuation of ABC and close patient monitoring [5,6].

However, conducting more comprehensive studies would provide a better understanding of the prevalence of HLA-B*57:01 in Saudi Arabia.

Conclusion

The prevalence of HLA-B*5701 among HIV-1-infected patients in Saudi Arabia was low. Additionally, suspected ABC HSR is uncommon in individuals who test negative for HLA-B*57:01.

Although the prevalence of HLA-B*57:01 in our population is low, it is still cost-effective to check for the allele before starting an ABC-containing regimen to avoid the high morbidity associated with ABC HSR, which, in addition to its severe adverse effects on patients’ health, would increase the cost of management.

Declarations

Author contributions: RA conceptualized and designed the study and drafted the manuscript. RA and AN carried out the statistical analysis. BM contributed to the study design. RA, AN, BM, SA, SK, AA, OA, AA, NA provided patients, contributed to their interpretation of data and critically revised the manuscript. All authors reviewed and approved the final manuscript.

Funding: No funding of any kind has been received; this data has been generated as part of the routine work of the hospitals.

Availability of data and materials: The datasets used and/ or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate: The study protocol was approved by the institutional review board of Ministry of health, Jeddah, Saudi Arabia. We confirm that all methods were carried out in accordance with relevant guidelines and regulations of Helsinki declaration. The informed con- sent was waived by the Research Ethics Committee of Ministry of health

Competing interests: The authors declare that they have no competing interests.

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