Despite the increase in ART coverage in Nigeria from 4% in 2004 to 55% in 2017, we did not observe a consistent decline in the prevalence of KS among adults who initiated in HIV care at this large HIV treatment facility in Jos, Nigeria. Compared to the baseline period (2006-2009), the age- and sex-adjusted prevalence of KS was nearly three times higher in the subsequent period (2010-2013; OR 2.81, 95% CI 1.82-4.34). Although the prevalence of KS subsequently declined in the most recent period (2014-2017), it remained higher, but not statistically different, from the baseline period. Overall, men had 53% higher odds of presenting with KS compared to women, and the odds for having KS at initial presentation declined by 13% for every 100 cells/mm3 increase in baseline CD4 T-cell count.
The reason for the higher prevalence of KS in 2010-2014 compared to 2006-2009 is unclear. Given the increase in ART coverage in the country, the marginally higher median CD4 T-cell in 2010-2014 compared to 2006-2009, and the known inverse relationship between CD4 T-cell count and KS, the higher prevalence of KS in 2010-2014 was unexpected. While this increase in KS prevalence may be due to the ineffectiveness of interventions to address the burden of HIV and its co-morbidities, this may not always be the case[2, 29]. In a Ugandan cohort, an increase in KS prevalence during a period of ART expansion was attributed to a clinical trial for which patients with KS were actively recruited. That was however not the case in the present cohort. Paradoxically, increased ART coverage may lead to a transient increase in KS prevalence at enrollment, as sick patients from previously unreached communities gain access to HIV care. Community-based studies would be needed to evaluate this hypothesis. Irrespective of the cause, the trend is troubling and calls for continuous routine monitoring of KS burden in patients initiating HIV care.
An important driver of KS risk in this population was the late initiation of HIV care. In the present cohort, 73 % of patients had a baseline CD4 T-cell count below 350 cells/mm3, thereby meeting the case definition for late presentation for HIV care. Using the full definition for late presentation which includes the presence of an AIDS-defining event, the proportion of patients presenting late was above 80%. An earlier study in this HIV cohort similarly showed that over 80% of patients initiating HIV care between 2005 and 2010 presented late, with a marginal decline from 88.9% in 2005 to 80.1% in 2010. While late presentation to care has been reported in HIV cohorts in various countries, its burden is greater in low- and middle-income countries, compared to high-income countries[30, 31]. Due to the high seroprevalence of HHV-8 among adults with HIV in Nigeria[11, 12], timely HIV diagnosis and linkage to care may be the only viable intervention to significantly reduce the prevalence of KS in adults initiating HIV care.
Several studies have reported a higher risk of HIV-associated KS in males compared to females[22-24, 32]. In North America and Europe cohorts, it was attributed to the risk of co-transmission of HIV and HHV-8 through sex in men who had sex with men (MSM), who constituted the largest HIV risk group[32-35]. In Nigeria and most of SSA, heterosexual sexual activity is the major route of HIV transmission, yet many studies have reported a higher KS prevalence in males, suggesting that there are other unexplained mechanisms[22-24]. In addition to the higher odds for KS in males, a striking, but incidental finding in the current study is the CD4 T-cell dependent difference in KS risk between males and females. KS prevalence in females appeared to be more sensitive to changes in CD4 T-cell count changes, with a significantly lower risk for KS occurring between CD4 T-cell counts of 200-500 cell/mm3. In contrast, for advanced immunosuppression (CD4 T-cell count < 200 cells/mm3) or normal CD4 T-cell count (above 500 cell/mm3); the difference was not significant. To the best of our knowledge, this is the first study to describe sex-based differences in the association between CD4 T-cell and KS prevalence. Sex-based differences in the association between CD4 T-cell and disease severity has however been reported in other diseases[25, 36]. This finding needs to be verified in other populations and its implications for KS prevention examined.
The findings of this study need to be interpreted in the context of its limitations. First, this is a single-center study from a tertiary health facility which is a center for excellence for HIV care. The study population may, therefore, differ from those of patients initiating HIV care in other facilities in Nigeria. Another limitation is that not all cases of KS were histologically confirmed, which may lead to misclassification and errors in the estimate of KS prevalence. Also, since routinely collected clinical data were evaluated, unmeasured factors such as training of health providers may have led to increased recognition and documentation of KS cases. Although rare, patients with visceral KS alone may have been missed due to lower resources for diagnostic testing such as CT scans, bronchoscopy, and endoscopy leading to underestimation of KS prevalence. Also, since the study was limited to adults initiating HIV care, the results may not provide a reliable estimate of changes in the prevalence of HIV-associated KS in the community.
Despite these limitations, a key strength of this study is its large sample size and 12-year time span which provided sufficient power to precisely assess KS prevalence and evaluate changes over significant periods of ART expansion in Nigeria. While routinely collected clinical data were utilized, the JUTH HIV clinic has rigorous protocols to maintain a high-quality database, which is routinely used for research[13, 20, 37]. Recent funding support from the US National Institute for Health has also supported the validation of cancer cases within the database. Lastly, although the study was conducted among patients in just one clinic, the age, sex, and CD4 T-cell count distribution of patients in this cohort were similar to reports from other large HIV cohort across Nigeria[27, 38].
The findings from this study have important implications for HIV care providers, researchers, and policymakers. Despite the relatively low KS prevalence among Nigerians initiating HIV care, KS prevalence has not appreciably declined (even since the 1990s) despite the expansion of ART coverage. Considering its large HIV population, Nigeria is an important contributor to the global burden of HIV-associated KS. In addition to interventions aimed at reducing HIV transmission, those targeted at timely HIV diagnosis and linkage to care may be most effective in reducing the prevalence of KS among patients initiating HIV care. This includes increased access to HIV testing, including home-based testing, to aid early HIV diagnosis. Currently, only about 37% of Nigerians have access to quality HIV testing services, which is an essential first step along the cascade of HIV care and treatment. Following HIV diagnosis, innovative and effective ways to link newly diagnosed patients to access care need to be identified and deployed.
In conclusion, despite increases in ART coverage, this study did not find a decline in the KS prevalence among adults initiating HIV care in Jos, Nigeria. Even in the most recent era of HIV care (2014-2017), over 50% of patients had advanced HIV disease at first presentation, putting them at high risk for KS. Strategies to aid early HIV diagnosis and entry into care in low-resource and high HIV burdened countries are needed as this may present the most effective approach to prevent HIV-associated KS globally.