INTRODUCTION

Kaposi’s sarcoma (KS) is the most common cancer in people living with HIV (PLWHA) in developing countries ¹. Antiretroviral therapy (ART) has successfully reduced the incidence of KS worldwide ^{2 , 3}; however, the risk of KS remains high in resource-poor countries, where treatment is still not universally available or free of charge.

Human herpesvirus 8 (HHV-8) is the etiologic agent of KS, and is a necessary but not sufficient cause for developing this disease ⁴. Seroprevalence varies geographically between continents, being higher in regions such as Africa and Latin America ⁵ and less prevalent in Europe and North America ⁴. It is also highly prevalent among men who have sex with men (MSM), particularly those with HIV co-infection ^{6 , 7}.

In Peru, ART has been administered since 2004, when the Ministry of Health (MINSA) approved the ruling for its free distribution in public hospitals. Since then, as in the rest of the world, the impact has been decisive in reducing the number of cases of opportunistic infections and HIV-related neoplasms. In 2006, Mohanna et al. reported that the incidence of epidemic KS was 20.26 per 1000 HIV patients treated between 1987 and 2003, with a male:female ratio of 15:1 ⁸.

This study aimed to describe the demographic, clinical, laboratory and therapeutic characteristics of patients with HIV who developed KS over a period of time, as well as to evaluate the characteristics of cases who developed KS, regardless of CD4 lymphocyte count.

THE STUDY

FINDINGS

We identified 129 KS cases between 2000 and 2018. The median age at diagnosis was 33 years (IQR: 28-41). Most were male (92.3%, 119/129) and of these, more than two-thirds (88/129) were reported as MSM, compared to all women who were reported as heterosexual. The median time from HIV diagnosis to KS diagnosis was 4 months, most (65.9%, 85/129) were diagnosed during the first year, after HIV diagnosis. The median CD4 lymphocyte count was 64 cells/µL (IQR, 33-185); however, 17.8% (23/129) had more than 200 cells/µL at KS diagnosis. The demographic and clinical characteristics of the patients are summarized in Table 1.

Cutaneous involvement was the most common presentation in 80.6% (104/129) of the patients, and of these, 38.0% (49/129) also developed the visceral form. Regarding visceral involvement, the gastrointestinal system was the most affected (Table 2). On the other hand, more than half of the patients received chemotherapy, with paclitaxel being the most commonly used drug. ART as the only treatment was received by one third of the patients. There was an increase in the number of KS cases per calendar year, due to the improvement of the data collection system and the fact that more patients were enrolled in the COVIHS each year.

Table 3 describes the information of the eight cases that presented CD4 lymphocyte counts above 300 cells/µL at the time of KS diagnosis. The median age was 36.5 years (IQR: 29-41.5); there was only one female and all males reported their sexual orientation as MSM. The median time from HIV diagnosis to KS diagnosis was 27.1 months (IQR: 5.7-104.2); the median CD4 lymphocyte count was 375 cells/µL (IQR: 312-489.5) and the median Log10 viral load was 2.1 copies/ml (IQR: 1.5-4.8). Skin and visceral disease were reported in 5 and 3 cases, respectively. Only six patients were being treated with ART prior to KS diagnosis and five received chemotherapy as targeted therapy for KS.

DISCUSSION

KS remains the most frequent type of cancer in low- and middle-income settings ⁹. Our results are comparable with those published worldwide ¹⁰. Among the main findings, we highlight that this neoplasm is predominantly found in young males, with sexual orientation toward MSM, with CD4 lymphocyte counts below 100, detectable viral load, and with visceral presentation in more than 50% of cases.

Bohlius et al. conducted a multiregional cohort study in all five continents. They found that, in three of the four regions, men were the largest group, 94% in Latin America, 93% in North America and 90% in Europe ⁴, which is similar to our findings; however, in South Africa, women were the more affected than men, probably due to the higher female prevalence of HIV in that continent. On the other hand, a much higher median age at KS diagnosis was found in North America and Europe, 42.9 years (IQR: 37.6-48.7) and 40.2 years (IQR: 34.1-47.8), respectively ⁴. Also, in these regions, MSM were found to be at higher risk of developing KS, in contrast to heterosexual men or women, whose frequency ranged from 65% to 75% for the Americas and Europe, probably due to the high rates of co-infection with HVH-8 among MSM ¹¹. Our study describes a median CD4 lymphocyte count at KS diagnosis of 64 cells/µL (IQR: 33-185), which is comparable to that described in other continents; however, a higher median is described in higher income countries, such as North America and Europe, 87 cells/µL (IQR: 20-280), 180 cells/µL (IQR: 60-348), respectively ⁴.

Although ART has brought great benefits, KS is now associated with higher CD4 lymphocyte count levels, even in treatment-adherent patients ^{12 , 13}. Studies have documented this finding on CD4 lymphocyte count trends since Maurer et al. reported a group of nine HIV patients on ART who developed KS in the context of good immune status (CD4 greater than 300 cells/µL) and undetectable viral load ¹⁴.

Accordingly, our study found eight individuals with CD4 lymphocyte counts above 300 cells/µL and, of these, six with undetectable viral load. Some authors have hypothesized that the high number of elderly patients might alter the integrity of the immune system in long-term HIV infection ¹⁵. However, Unemori et al. in 2013, explored the possible mechanisms of this phenomenon and found that progressive loss of immune function during advanced age, referred to as immunosenescence, could be directly associated with the development of KS ¹⁶.

The main limitation of this study was information bias, because of the retrospective design over a period of 18 years. The information was limited to what was available in a database and to what was additionally obtained from the review of medical records of patients who were still alive. Another limitation was selection bias, since all patients with HIV who developed KS were selected. However, the actual number of cases was underestimated, due to the lack of data collection techniques in the past, so the prevalence or incidence of this disease could not be determined.

In conclusion, the characteristics associated with KS found in our setting were similar to those described in the literature. It is predominantly found in young males with sexual orientation towards MSM, with low CD4 lymphocyte counts. Cutaneous involvement was the most frequent presentation, and at least half had associated visceral involvement. It is also important to highlight that, in this series, as in others described recently, patients with KS with CD4 lymphocyte counts above 300 cells/µL were also identified.