Prevalence and associated risk factors for Kaposi’s sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study

Kaposi’s sarcoma (KS) was first described in 1872 by Moritz Kaposi, a Hungarian dermatologist, who described KS as a rare multifocal angioproliferative tumour involving blood and lymphatic vessels, occurring only in Eastern Europe and the Mediterranean [1]. KS is a cancer that causes lesions to grow in the mucosa such as skin, mucous membranes lining the mouth, nose, throat or viscerally in lymph nodes, or other internal organs [1, 2]. KS presents as either red, brown or purple lesions that can be typed into different clinicopathological forms, such as patch, plaque, nodular, lymphadenopathic or infiltrative ulcers. It can also present as florid severe swellings in the arms, legs, face or scrotum. The etiological agent associated with KS was discovered in 1994 and is called Human Herpes Virus 8 (HHV8), also known as KS-associated Human Herpes Virus (KSHV) [1, 3]. There are 4 classes of KS, which include; Classic KS, Endemic KS, Immunosuppression-associated KS and AIDS-associated KS [4]. AIDS-associated KS is the most prevalent form of KS, and its prevalence tremendously increased post-HIV era but later declined due to introduction of Anti-Retroviral Therapy (ART). However, KS still remains one of the leading cancers in HIV-infected individuals, especially in sub-Saharan Africa, including Tanzania [5, 6]. Uldrick et al., reported post-HIV seroprevalence of KSHV as very common in sub-Saharan Africa, with seropositivity rates above 50%; moderately prevalent in Mediterranean countries (20–30%), but much less common (< 10%) in most of Europe, Asia and the US [7]. In Tanzania, the prevalence of AIDS-related KS was reported to be 2.4% at Bugando medical center in northwestern Tanzania from 2004 to 2014 [8], whereas Koski et al., reported prevalence of AIDS-associated KS to have dropped from 10.1% in 2003 to 7.4% in 2011 in a study conducted at Ocean Road Cancer Institute (ORCI), Tanzania [9]. A study conducted from 2006 to 2007 at The Kilimanjaro Christian Medical Centre (KCMC) Regional Dermatology Training Center (RDTC) and Mawenzi Regional Hospital Infectious Diseases Clinic in Moshi, northern Tanzania, reported a 4% prevalence of KS [10]. These studies show that KS is still prevalent in Tanzania. Furthermore, according to the International Agency for Research on Cancer 2012 report, KS accounts for approximately 12.3% of all cancer deaths in the East African region [6].

Several risk factors have been associated with high prevalence of KS in sub-Saharan Africa and East Africa. The major risk factors include HIV seropositivity and non-adherence to anti-retroviral therapy [9], as well as low CD4 cell levels [3, 11, 12]. In contrast, injecting drug users and homosexuals are the highest risk groups for KS in developed countries, such as the United States of America [11], where it is estimated that 30–40% of homosexual men infected with HIV are seropositive for HHV-8 [11]. Similar observations were made in India, where Munawwar et al., reported the major risk factor for KS among HIV patients to be seropositivity to HHV-8, which accounted for 26.0% in heterosexual men and 25% in men who had sex with other men (MSM) developed KS [13].

Treatment options for KS include surgical excision, radiation therapy and intralesional chemotherapy. These treatment options are used based on disease severity and available local treatment options. Highly Active Anti-Retroviral Therapy (HAART) is recommended to reduce the extent and size of KS lesions in HIV-related KS patients. However, recent reports have shown that ART resistance is on the rise in southern and eastern Africa and Latin America and, as a result, it may soon be necessary to change the recommended first-line antiretroviral drug regimen in many countries to integrase inhibitor-based treatment [14].

Generally, KS continues to be one of the leading AIDS-defining illnesses in Sub-Saharan Africa, including Tanzania, as well as one of the most prevalent cancers overall due to HIV and HHV-8 [13, 15]. In light of its importance in the HIV era, KS is thus a critical tumor to monitor on an annual and periodic basis, to assess the impact of different preventive and management strategies in place against the disease. The aim of this study was therefore to determine the prevalence of KS and associated risk factors among HIV positive patients who attended KCMC referral hospital in Kilimanjaro between 2012 and 2015.

We have reported a prevalence of 4.6% KS among HIV positive patients attending KCMC hospital in the 4-year study period from 2012 to 2015. This prevalence is slightly higher than that reported by Mavura et al., 2015 in the same region [10]. Furthermore, similar studies done within the past 5 years in the same area but in different settings, reported lower prevalence of KS. These studies were conducted in South Africa, northwestern Tanzania, and northern Tanzania, and reported prevalences of 3.4, 2.4 and 4% respectively. Other studies conducted in mediterranean countries and within the East African region [6] reported KS prevalence of 10–20, and 12.3%, which is higher than what we have reported herein. These differences may be due to heterogeneity in the distribution of KS within Tanzania as well as elsewhere. This may also be contributed by other factors, including length of the study period, under/over reporting and misdiagnosis.

Our data showed an association between CD4 cell count and KS, where low CD4 cell count (≤200) was associated with increased odds for KS 28.4 fold (p = 0.003). Similar observations were made by other studies conducted in Nigeria [16] and northwestern Tanzania [8]. These similar findings strongly suggest that a low CD4 cell count is associated with KS. A possible explanation for this is that KS strongly impacts on immune responses. More studies on immune response mechanisms in KS will possibly help provide explanations for observed differences in prevalence of KS and CD4 cell count.

Furthermore, our findings pointed out that the HIV positive non-ART users were not more associated with KS compared to ART users. Use of ART was not shown to have a protective effect against HIV and thus KS as previously shown by other investigators from different geographical areas [9, 12]. Most patients at the time of this study were eligible for ART if they presented WHO HIV stage IV or with CD4 cell counts < 200 cells/μl. The protective role of ART against KS has been explored extensively by other investigators [13, 18]. ART raises body immunity in HIV infected persons, and this may indirectly benefit KS patients, therefore the interaction between HIV-KS and ART should be further investigated. Early initiation of ART as per newly established WHO standards is also highly encouraged as it may as well be protective against KS. However, there are increasing concerns of ART resistance worldwide and more so in East Africa [14, 17]. In addition to ART resistance, there are policy issues that need to be addressed to help people re-engage in care and reduce loss of patients from care, as these are important factors contributing to the development of drug resistance [18]. ART drug resistance was reported to be around 14.9% in ART-naïve patients in Tanzania in 2008 and has risen to 25.4% in 2016 [19, 20].

Our study findings showed that females were more likely to be diagnosed with KS compared to males (p < 0.009). This observation is different from that reported in other studies conducted in Nigeria [21] and Dar-es-salaam [9] by Kagu et al., 2006 and Koski et al., 2015, respectively, as well as by Ferlay et al., who reported an incidence of 5.5 in males against 2.9 in females [5]. Reasons for this disparity are yet to be elucidated. Moreover, a study done in northwestern Tanzania reported AIDS-related KS to be more severe and to progress faster in females. The study did not identify reasons for the disparity, but ruled out association with immunological responses since there was no significant difference between CD4 cell counts in males and females [8].

Our study observed age to be significantly associated with KS. Patients over 35 years were 25.7 times more likely to have KS than the age groups below (p < 0.007). Similar findings were reported in studies conducted elsewhere [10]. This may be explained by reduction of immunity as people get older, putting them at increased risk for age-related chronic diseases, including cancer.

Treatment of HIV patients by traditional healers had increased risk for suffering from KS. This may be explained by traditional healers contributing to delaying of ART usage by HIV patients in the process of seeking treatment from the healers, thus increasing their risk for KS. The same finding was observed in Cameroon [22, 23].

Our results generally show that there is still need for more well-defined approaches in curbing KS among the HIV seroconverted patients. Moreover, the ongoing interventions need to be strengthened, especially early initiation of ART regardless of CD4 cell count as recommended by the WHO, because ART has been associated with better prognosis and prolonged life of HIV-positive patients, including lowering of KS seroprevalence when proper adherence is observed. Other interventions include increasing awareness among HIV patients on compliance/adherence to ART; nutritional care and support for people living with HIV/AIDS to improve their immunity and adherence to ART; health care education especially as patients’ age, as well as health seeking attitude. We also propose that monitoring of ART resistance and virological failure, as reported by other investigators, should also be carried out in Tanzania. Although we have not directly studied this, we propose that there could be an association between increased KS prevalence and virological failure, as reported to be an emerging issue in HIV patient care.

KS remains a common malignant vascular tumour commonly associated with HIV/AIDS in Tanzania. The prevalence of KS among HIV-positive patients at KCMC referral hospital during 2012–2015 period has been found to be 4.6%, and has remained around 4% in Northern Tanzania. Our study highlights the need for continued efforts in combating HIV, including combating its associated diseases like KS. Continued availability of test reagents for CD4 count and viral load determination, and early initiation of ART to HIV/AIDS patients will alleviate the suffering of these patients. Further studies on ART resistance are highly needed to guide decisions on appropriate HV/AIDS management.