Survival of patients with Kaposi’s sarcoma in the South African antiretroviral treatment era: A retrospective cohort study

Background. When South Africa (SA) implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIV-positive Kaposi’s sarcoma (KS) patients shifted from symptomatic palliation to potential cure. Objective. To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA. Methods. We conducted a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012. We used Kaplan-Meier survival functions to estimate 1- and 2-year survival, and Cox regression models to identify changes over time and prognostic factors. Results. Our study included 357 AIDS-KS patients, almost all of whom were black Africans (n=353, 98.9%); 224 (62.7%) were men. The median age at cancer diagnosis was 37 (interquartile range (IQR) 30 - 43) years, and the median baseline CD4+ count was 242 (IQR 130 - 403) cells/µL. Most patients received ART (n=332, 93.0%) before or after KS diagnosis; 169 (47.3%) were treated with chemotherapy and 209 (58.6%) with radiation therapy. Mortality was 62.7% lower (adjusted hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.19 - 0.73) in the late (2009 - 2012) than in the early (2004 - 2008) ART period. Receiving chemotherapy (adjusted HR 0.3, 95% CI 0.15 - 0.61) and poor-risk AIDS Clinical Trials Group KS stage (adjusted HR 2.88, 95% CI 1.36 - 6.09) predicted mortality. Conclusions. Our results show that large national ART roll-out programmes can successfully reduce KS-related mortality at the individual patient level. If ART coverage is extended, KS-associated morbidity and mortality are likely to drop

Survival of patients with Kaposi’s sarcoma in the South African antiretroviral treatment era: A retrospective cohort study

Background. When South Africa (SA) implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIV-positive Kaposi’s sarcoma (KS) patients shifted from symptomatic palliation to potential cure.Objective. To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA.Methods. We conducted a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012. We used Kaplan-Meier survival functions to estimate 1- and 2-year survival, and Cox regression models to identify changes over time and prognostic factors.Results. Our study included 357 AIDS-KS patients, almost all of whom were black Africans (n=353, 98.9%); 224 (62.7%) were men. The median age at cancer diagnosis was 37 (interquartile range (IQR) 30 - 43) years, and the median baseline CD4+ count was 242 (IQR 130 - 403) cells/µL. Most patients received ART (n=332, 93.0%) before or after KS diagnosis; 169 (47.3%) were treated with chemotherapy and 209 (58.6%) with radiation therapy. Mortality was 62.7% lower (adjusted hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.19 - 0.73) in the late (2009 - 2012) than in the early (2004 - 2008) ART period. Receiving chemotherapy (adjusted HR 0.3, 95% CI 0.15 - 0.61) and poor-risk AIDS Clinical Trials Group KS stage (adjusted HR 2.88, 95% CI 1.36 - 6.09) predicted mortality.Conclusions. Our results show that large national ART roll-out programmes can successfully reduce KS-related mortality at the individual patient level. If ART coverage is extended, KS-associated morbidity and mortality are likely to drop.

Spatiotemporal modelling and mapping of cervical cancer incidence among HIV positive women in South Africa: a nationwide study

Background Disparities in invasive cervical cancer (ICC) incidence exist globally, particularly in HIV positive women who are at elevated risk compared to HIV negative women. We aimed to determine the spatial, temporal, and spatiotemporal incidence of ICC and the potential risk factors among HIV positive women in South Africa. Methods We included ICC cases in women diagnosed with HIV from the South African HIV cancer match study during 2004–2014. We used the Thembisa model, a mathematical model of the South African HIV epidemic to estimate women diagnosed with HIV per municipality, age group and calendar year. We fitted Bayesian hierarchical models, using a reparameterization of the Besag-York-Mollié to capture spatial autocorrelation, to estimate the spatiotemporal distribution of ICC incidence among women diagnosed with HIV. We also examined the association of deprivation, access to health (using the number of health facilities per municipality) and urbanicity with ICC incidence. We corrected our estimates to account for ICC case underascertainment, missing data and data errors. Results We included 17,821 ICC cases and demonstrated a decreasing trend in ICC incidence, from 306 to 312 in 2004 and from 160 to 191 in 2014 per 100,000 person-years across all municipalities and corrections. The spatial relative rate (RR) ranged from 0.27 to 4.43 in the model without any covariates. In the model adjusting for covariates, the most affluent municipalities had a RR of 3.18 (95% Credible Interval 1.82, 5.57) compared to the least affluent ones, and municipalities with better access to health care had a RR of 1.52 (1.03, 2.27) compared to municipalities with worse access to health. Conclusions The results show an increased incidence of cervical cancer in affluent municipalities and in those with more health facilities. This is likely driven by better access to health care in more affluent areas. More efforts should be made to ensure equitable access to health services, including mitigating physical barriers, such as transportation to health centres and strengthening of screening programmes

Cervical cancer in women living in South Africa: a record linkage study of the National Health Laboratory Service and the National Cancer Registry.

Introduction In countries with high HIV prevalence, it is important to understand the cervical cancer (CC) patterns by HIV status to ensure targeted prevention measures. We aimed to determine the factors associated with CC compared to non-infection related cancer in women living in South Africa. Methods This was a cross-sectional study of women aged 15 years and older diagnosed with CC and non-infection related cancer in the South African public health sector from 2004 to 2014. The National Cancer Registry provided data on cancer, whilst HIV status was determined from routinely collected HIV related data from the National Health Laboratory Service. We explored the association of HIV infection, age, ethnicity and calendar period with CC compared to non-infection related cancer. Results From 2004 to 2014, 49,599 women were diagnosed with CC, whilst 78,687 women had non-infection related cancer. About 40% (n = 20,063) of those with CC and 28% (n = 5,667) of those with non-infection related cancer had a known HIV status. The median age at CC diagnosis was 44 years (interquartile range (IQR): 37-52) and 54 years (IQR: 46-64) for HIV positive and negative women, respectively, and for non-infection related cancer, 45 years (IQR: 47-55) and 56 years (IQR: 47-66) for HIV negative and positive women, respectively. Diagnosis of CC was associated with HIV positivity, Black ethnicity, earlier calendar period (2004-2006) and the ages 30-49 years. In comparison with Black women, the odds of CC were 44% less in Coloured women, 50% less in Asian women and 51% less in White women. Conclusions HIV positive women presented a decade earlier with CC compared to HIV negative women. A large proportion of women with CC were unaware of their HIV status with a disproportionate burden of CC in Black women. We recommend women attending CC screening facilities to be offered HIV testing so that recommendations for their follow-up visits are given according to their HIV status

Comparison of Kaposi Sarcoma risk in human immunodeficiency virus-positive adults across 5 continents: A multiregional multicohort study

Background: We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results: We included 208 140 patients from 57 countries. Over a period of 1 066 572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100 000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts 65700 cells/\u3bcL with those whose counts were <50 cells/\u3bcL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by 6595% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional, and global level in 2020. Proportions of cervical cancer a) diagnosed in women living with HIV (WLHIV), and b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted towards younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention

Cervical cancer risk in women living with HIV across four continents: A multicohort study

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities

Survival of patients with Kaposi's sarcoma in the South African antiretroviral treatment era: A retrospective cohort study.

BACKGROUND When South Africa (SA) implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIV-positive Kaposi's sarcoma (KS) patients shifted from symptomatic palliation to potential cure. OBJECTIVE To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA. METHODS We conducted a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012. We used Kaplan-Meier survival functions to estimate 1- and 2-year survival, and Cox regression models to identify changes over time and prognostic factors. RESULTS Our study included 357 AIDS-KS patients, almost all of whom were black Africans (n=353, 98.9%); 224 (62.7%) were men. The median age at cancer diagnosis was 37 (interquartile range (IQR) 30 - 43) years, and the median baseline CD4+ count was 242 (IQR 130 - 403) cells/µL. Most patients received ART (n=332, 93.0%) before or after KS diagnosis; 169 (47.3%) were treated with chemotherapy and 209 (58.6%) with radiation therapy. Mortality was 62.7% lower (adjusted hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.19 - 0.73) in the late (2009 - 2012) than in the early (2004 - 2008) ART period. Receiving chemotherapy (adjusted HR 0.3, 95% CI 0.15 - 0.61) and poor-risk AIDS Clinical Trials Group KS stage (adjusted HR 2.88, 95% CI 1.36 - 6.09) predicted mortality. CONCLUSIONS Our results show that large national ART roll-out programmes can successfully reduce KS-related mortality at the individual patient level. If ART coverage is extended, KS-associated morbidity and mortality are likely to drop

Predictors of loss to follow-up among children in the first and second years of antiretroviral treatment in Johannesburg, South Africa

Ninety percent of the world's 2.1 million HIV-infected children live in sub-Saharan Africa, and 2.5% of South African children live with HIV. As HIV care and treatment programmes are scaled-up, a rise in loss to follow-up (LTFU) has been observed. The aim of the study was to determine the rate of LTFU in children receiving antiretroviral treatment (ART) and to identify baseline characteristics associated with LTFU in the first year of treatment. We also explored the effect of patient characteristics at 12 months treatment on LTFU in the second year. The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Children's Clinic (HSCC) in Soweto, Johannesburg. Cox proportional hazards models were fitted to investigate associations between baseline characteristics and 12-month characteristics with LTFU in the first and second year on ART, respectively. The cumulative probability of LTFU at 12 months was 7.3%. In the first 12 months on ART, independent predictors of LTFU were age B1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight. Among children still on treatment at 1 year from ART initiation, characteristics that predicted LTFU within the second year were recent year of ART start, mother as a primary caregiver, being underweight, and low CD4 cell percentage. There are similarities between the known predictors of death and the predictors of LTFU in the first and second years of ART. Knowing the vital status of children is important to determine LTFU. Although HIV-positive children cared for by their mothers appear to be at greater risk of becoming LTFU, further research is needed to explore the challenges faced by mothers and other caregivers and their impact on long-term HIV care. There is also a need to investigate the effects of differential access to ART between mothers and children and its impact on ART outcomes in children.