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Impact of Antiretroviral Therapy eligibility expansion on the epidemiology of HIV-associated Kaposi Sarcoma in Nigeria

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Abstract Kaposi sarcoma (KS) is the most common cancer associated with human immunodeficiency virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS) infection worldwide and it is the most prevalent cancer in some countries in sub-Saharan Africa (SSA). The introduction of combination antiretroviral therapy (ART), led to dramatic declines in KS morbidity and mortality, particularly in North America and Europe where there has been widespread access to ART. In SSA, however, some countries continue to high morbidity and mortality from HIV-associated KS. In 2018, SSA accounted for 60% of global KS cases and 90% of KS deaths. The late emergence of ART in SSA has been identified as an important contributor to the high burden of KS in the region. As countries in the region expand ART access, there are indications that the burden of KS in some countries is on the decline . Nigeria has the second-largest HIV epidemic in the world (second only to South Africa) and has significantly expanded in its ART coverage over the last decade; from 4% in 2005 to 55% by the end of 2018 . In line with the recommendations of the World Health Organization (WHO), Nigeria has adopted newer HIV treatment guidelines advocating for earlier ART initiation. While this progress has the potential to reduce the KS burden in the country, the impact of HIV treatment expansion of the epidemiology of HIV-associated KS in Nigeria has not been systematically studied. To address this gap, longitudinal data of adults who initiated HIV at the Jos University Teaching Hospital HIV Clinic, one of Nigeria’s largest HIV clinical cohorts, from January 2006 to December 2017, were analyzed to (1) Describe trends in KS prevalence at the time of initiation of HIV care among adults who initiated HIV care between 2006 and 2017 in Jos, Nigeria; (2) Determine the impact of ART eligibility expansion on the incidence of Kaposi Sarcoma among adults with HIV in Nigeria; and (3). Investigate the effect of ART eligibility expansion on outcomes of HIV-associated Kaposi Sarcoma in Nigeria. Among adults who initiated HIV care from January 2006 to December 2017, the prevalence was lowest from 2006-2009 (0.39%, 95% CI 0.29-0.53), peaked at 1.12% (95% CI 0.82-1.52) from 2010-2013 and declined to 0.72% (95% CI 0.42-1.20) from 2014-2017. Compared to the 2006-2009, age and sex adjusted odds for KS were higher in 2010-2013 (OR 2.81 (95% CI 1.83-4.34, p<0.01)), but subsequently declined in 2014-2017 (OR 1.74 (95% CI 0.95-3.30, p=0.07). Among adults who were KS-free at the time of initiation of HIV care, the crude incidence of KS was lower after the ART-eligibility expansion (2010-2016) compared to the pre-expansion period (2006-2009) (1.58/1,000 person-years versus 2.53/1,000 person-years; Log-rank p<0.01). Age- and sex-adjusted incidence of KS was 39% lower patients who initiated HIV care in 2010-2016 compared to 2006-2009 (HR 0.61, 95% CI 0.5-0.69, p<0.01). When observation time commenced on the date of ART initiation, instead of the date of initiation of HIV care, the age-, sex-adjusted incidence of KS was 49 % lower in patients who initiated HIV care in 2010-2016, compared to the 2006-2009 cohort (HR 0.51; 95% CI 0.27-0.98, p=0.04). However, after adjusting for age, sex, and baseline CD4 T-cell count, only sex was independently associated with incident KS (Female HR 0.59; 95% CI 0.36-0.98, p=0.04; male reference). Among adults who initiated HIV care from January 2006 to December 2016, after a median period of 3.5 years, 28.9% were alive and in-care at the clinic,12.2% had transferred care to other facilities, 50.7% were LTFU and 8.6% had died. The cumulative hazard for the composite outcome of death or LTFU was 67% higher in the post-expansion period compared to the pre-expansion period (HR 1.67, 95% CI 1.13-2.48, p<0.01), and this difference persisted after adjusting for age, sex, first-line ART category (NNRTI, triple nukes, PI, or none), and CD4-T cell count category (HR 1.70 (1.14-2.56, p=0.01). This difference was due to the significantly higher risk of LTFU in the post-expansion compared to the pre-expansion period. The adoption of expanded ART treatment guidelines was followed by a reduction in the incidence of HIV-associated KS among adults initiating HIV in Jos, Nigeria. However, there was no significant decline in the prevalence of KS among adults initiating HIV care. Also concerning is the higher risk of LTF in patients with HIV-associated KS after the expansion of HIV treatment guidelines. Having a diagnosis of KS at the time of enrollment for HIV care is indicative of late presentation. As the HIV treatment program in Nigeria expands, policymakers and public health departments must focus on programs that will aid early HIV diagnosis and engagement in care. This will enable Nigeria to reap the full benefits of ‘treatment for all’ policy which was implemented in 2016. Also, HIV treatment providers, ART programs, policymakers, and health services researchers need to find innovative methods to ensure that patients remain engaged in long term HIV care.

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