In the present study, we have described the CCR5-Δ32 and HLA-B*57:01 alleles in HIV-exposed seronegative and HIV-1 seropositive Peruvian individuals and collected social, clinical and epidemiological information for each participant. In the case of CCR5-Δ32, our findings reveal that the prevalence of this mutation was low, which could be related to the low degree of admixture detected between the current Peruvian population and the European population, primarily Spanish¹⁰. The sample of Peruvian individuals analyzed in this study did not present any homozygous case for the CCR5 mutation, consistent with the results from previous studies in Latin American countries^8,14,15.

In contrast to our data, Solloch et al.⁸ reported a higher prevalence for CCR5-Δ32 (5% versus 3%). This difference, albeit small, could be related to the methodology used, the size of the sample and the selection of the population. In addition, Solloch et al.⁸ did not provide further information on the individuals’ backgrounds, making it difficult to assess how the degree of admixture among Peruvians varies by geographical origin. In our study, we included participants from 18 cities in Peru, primarily from Lima, Lambayeque and Loreto—regions known for having the highest genetic variability in the country¹². These data suggest that the selected populations might be representative of Peru; however, further nationwide studies are needed to confirm this.

Regarding the HLA-B*5701 allele, our study showed a lower frequency than CCR5-Δ32, which could be due to its higher distribution in Caucasian populations than in Latin American or Native American populations^16,17. The allele frequency in some Latin American countries ranged from 1% to 5.6% (refs.^16,17,18,19), suggesting that the degree of admixtures with the European lineage is variable. Martínez et al.¹⁷, who reported a prevalence of 2.7% among HIV-infected Colombians, found that, when the sample was stratified according to ethnic characteristics, the prevalence was higher in white individuals (4%) than in other ethnic groups such as mestizos (2.6%) or Afro-Colombians (1.9%). These results show that the allele distribution in Latin America may differ depending on the local ethnic characteristics of each country, suggesting that the degree of admixture in this population is higher than in other regions of the world.

On this last point, the study published by Vilcarino et al.¹¹ found a frequency of 4% in a sample of 49 Peruvian participants. However, the data on the geographical origin of these samples are limited, as most of them included only individuals from the same city. In addition, the sample size was very small, so this value could not be considered representative of the Peruvian population. By contrast, the sample size in this study was larger (n = 300) and from different regions of Peru (Table 1). Considering that the Allele Frequency Net database (https://www.allelefrequencies.net/) lacks data on the prevalence of this allele in Peru, this study may be the first to provide approximate prevalence estimates of HLA-B*57:01 in the Peruvian population.

From a clinical point of view, the presence of both CCR5-Δ32 and HLA-B*57:01 have been associated with slow progression to AIDS in carrier individuals^1,3. Their presence in the Peruvian population opens the possibilities of finding a specific group of individuals with slow progression to AIDS. However, among carriers of the CCR5-Δ32 mutation, only one exhibited a viral load below 20 copies, while the others had viral loads exceeding 1000 copies. It is therefore possible that pharmacological and/or genetic factors may influence virological failure in carriers of this mutation.

The CD4 count was statistically significantly lower in PVV, which is to be expected because HIV infection is associated with a depletion of the CD4 lymphocyte population²⁰. However, when analyzing the immune response status of CCR5-Δ32 mutation carriers in the PVV group (PVV^CCR5/Δ32, n = 3), they showed more than 400 CD4⁺ cells/µl, a value outside the threshold for risk of developing AIDS²¹, and above the average CD4 of those who did not carry this mutation. The high proportion of CD4⁺ cells may be a consequence of CD30L overexpression associated with the 32-nucleotide deletion²². Another important detail related to the immune response is that the antiretroviral treatment currently being received by PVV^CCR5/Δ32 based on a combination of dolutegravir, tenofovir, lamivudine and efavirenz may also contribute to favoring the immune response against HIV, as has been described in a previous study²³. However, ex vivo experiments have shown that treatment with dolutegravir has the opposite effect, generating a decrease in the CD4 population²⁴. Considering that two individuals in the PVV^CCR5/Δ32 group were treated with this drug and still maintained a CD4 count greater than 400 cells/µl, we suggest that the CD4 population restoration is attributable to the mutation.

We collected the data regarding the risk behavior of CCR5-Δ32 mutation carriers from the PS group (PS^CCR5/Δ32, n = 5). They reported high-risk sexual behavior for HIV/Sexual Transmitted Infections such as multiple sexual partners, infection by sexual transmission, use of recreational drugs and intermittent condom use. In spite of this, they had a good immune response (an average of 1,011.4 cells/µl) and a negative diagnosis of HIV at quarterly or half-yearly monitoring tests. These characteristics may be associated with the CCR5-Δ32 mutation, which, according to this study, was more prevalent in PS than in PVV, although not statistically significantly so. Because the statistical power calculation yielded a value of 0.091, this finding suggests a possible false negative due to the small sample size (n = 300) in this study. However, the possibility of other genetic or immunological factors contributing to a degree of resistance to PS should not be discounted. In fact, a recent exome study revealed a new allele HLA-DQB1*03:419 found in the Peruvian population associated with immunological protection (P < 0.04)²⁵. These findings highlight the need for further genomic research to identify new protective genes in different geographic regions of Peru.

The presence of a single individual with the HLA-B*57:01 allele among 300 HIV-positive and HIV-negative Peruvian individuals (0.3%) indicates the rarity of this allele in the Peruvian population. This fact may be related to the population’s predominantly indigenous genetic characteristics, even among the mestizo population, as demonstrated in previous studies^12,26. Considering the approximate HIV prevalence in the Peruvian population is 0.3% and that 89% of those diagnosed have access to antiretroviral therapy²⁷, the administration of ABC in this group would be exceptional. In fact, only 6 of the 150 HIV-positive participants in our study received ABC, confirming the limited access to this drug. Moreover, the Peruvian Technical Normative on Antiretroviral Therapy Recommendations does not mandate the use of this drug in first- or second-line therapy, which could explain why Peruvian doctors prescribe it as a second alternative, among other clinical reasons.

Regarding the administration of ABC, cohorts including more than 200,000 participants, mostly Caucasian, revealed that only 5–8% of cases presented hypersensitivity symptoms when treated with ABC²⁸. Likewise, only 6% of those with the mutation who manifested hypersensitivity reactions are at high risk²⁹.

Regarding the financial sustainability of the HLA-B*5701 test, it has been shown to be cost-effective in a US population³⁰; however, these estimates could vary in populations with high levels of interbreeding, such as the Peruvian population. In fact, a significant proportion of the Peruvian population is of indigenous descent, even among the mestizo population¹². Together, these data suggest reconsidering the value of routinely detecting this allele within Peru’s resistance surveillance and monitoring system, unless multicenter studies with representative sample sizes are conducted to define its national distribution. Given that our results indicate that achieving 80% statistical power requires recruiting over 50,000 participants, the cost-effectiveness of HLA-B*5701 testing for routine use could be disregarded. Based on the evidence from this study and current ABC management practices in Peru, it is possible that hypersensitivity cases in this country are very rare. However, these findings should be viewed with caution.

Finally, this study focuses on the genetic variants CCR5-Δ32 and HLA-B*57:01 in PVV and PS groups, and the results presented will support future studies in estimating more representative sample sizes across different geographical regions of Peru. It also demonstrates the need for local studies in search of markers to better understand HIV resistance in at-risk populations and to predict the prognosis of AIDS in the Peruvian population. The effects of CCR5-Δ32 in Peruvian individuals may differ from those described in European populations, due to genetic heterogeneity. These effects are influenced not only by allele frequency but also by interactions with other genes that may modulate CCR5-Δ32 expression individually or synergistically³¹.

In conclusion, our findings show that the prevalence of both CCR5-Δ32 and HLA-B*57:01 alleles is low, supporting evidence of limited recent gene flow between European populations and indigenous communities in present-day Peru. Similarly, the presence of one carrier of the HLA-B*57:01 allele—and two previously reported cases—demonstrates the ongoing surveillance of ABC hypersensitivity in the Peruvian population. However, further nationwide investigations covering each region of Peru are needed to obtain a truly representative sample of the Peruvian population.