Mazvita Sengayi

Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era.

The incidence of Kaposis Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV‐infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time‐updated CD4 cell counts and HIV‐1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person‐years follow‐up 162 patients developed KS. The incidence was 1,682/100,000 person‐years (95% confidence interval [CI] 1,406–2,011) among patients not receiving ART and 138/100,000 person‐years (95% CI 102–187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13–0.28). Low CD4 cell counts (time‐updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9–80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS‐associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

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

BACKGROUND Ninety percent of the worlds 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. OBJECTIVE 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. METHODS The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Childrens 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. RESULTS The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1-8.8). In the first 12 months on ART, independent predictors of LTFU were age <1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight (WAZ ≤ -2). 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 (WAZ ≤ -2), and low CD4 cell percentage. CONCLUSIONS 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.Background : Ninety percent of the worlds 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. Objective : 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. Methods : The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Childrens 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. Results : The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1–8.8). In the first 12 months on ART, independent predictors of LTFU were age <1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight (WAZ ≤ −2). 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 (WAZ ≤ −2), and low CD4 cell percentage. Conclusions : 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.

Record linkage to correct under-ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project.

The surveillance of HIV‐related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu‐Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non‐Hodgkins lymphoma and non‐AIDS defining cancers (NADCs) before and after inclusion of linkage‐identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV‐positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91–212) to 877 (95% CI 744–1,041) per 100,000 person‐years after inclusion of linkage‐identified cancers. Incidence rates were highest for KS (432, 95% CI 341–555), followed by cervix (259, 95% CI 179–390) and NADCs (294, 95% CI 223–395) per 100,000 person‐years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment.

South African National Cancer Registry: Effect of withheld data from private health systems on cancer incidence estimates

BACKGROUND The National Cancer Registry (NCR) was established as a pathology-based cancer reporting system. From 2005 to 2007, private health laboratories withheld cancer reports owing to concerns regarding voluntary sharing of patient data. OBJECTIVES To estimate the impact of under-reported cancer data from private health laboratories. METHODS A linear regression analysis was conducted to project expected cancer cases for 2005-2007. Differences between actual and projected figures were calculated to estimate percentage under-reporting. RESULTS The projected NCR case total varied from 53,407 (3.8% net increase from actual cases reported) in 2005 to 54,823 (3.7% net increase) in 2007. The projected number of reported cases from private laboratories in 2005 was 26,359 (19.7% net increase from actual cases reported), 27,012 (18.8% net increase) in 2006 and 27,666 (28.4% net increase) in 2007. CONCLUSION While private healthcare reporting decreased by 28% from 2005 to 2007, this represented a minimal impact on overall cancer reporting (net decrease of <4%).

Establishment of a cancer surveillance programme : the South African experience

Cancer is projected to become a leading cause of morbidity and mortality in low-income and middle-income countries in the future. However, cancer incidence in South Africa is largely under-reported because of a lack of nationwide cancer surveillance networks. We describe present cancer surveillance activities in South Africa, and use the International Agency for Research on Cancer framework to propose the development of four population-based cancer registries in South Africa. These registries will represent the ethnic and geographical diversity of the country. We also provide an update on a cancer surveillance pilot programme in the Ekurhuleni Metropolitan District, and the successes and challenges in the implementation of the IARC framework in a local context. We examine the development of a comprehensive cancer surveillance system in a middle-income country, which might serve to assist other countries in establishing population-based cancer registries in a resource-constrained environment.

Cervical cancer risk and impact of Pap-based screening in HIV-positive women on antiretroviral therapy in Johannesburg, South Africa.

Data on invasive cervical cancer (ICC) incidence in HIV‐positive women and the effect of cervical cancer screening in sub‐Saharan Africa are scarce. We estimated i) ICC incidence rates in women (≥18 years) who initiated antiretroviral therapy (ART) at the Themba Lethu Clinic (TLC) in Johannesburg, South Africa, between 2004 and 2011 and ii) the effect of a Pap‐based screening program. We included 10,640 women; median age at ART initiation: 35 years [interquartile range (IQR) 30–42], median CD4 count at ART initiation: 113 cells/µL (IQR 46–184). During 27,257 person‐years (pys), 138 women were diagnosed with ICC; overall incidence rate: 506/100,000 pys [95% confidence interval (CI) 428–598]. The ICC incidence rate was highest (615/100,000 pys) in women who initiated ART before cervical cancer screening became available in 04/2005 and was lowest (260/100,000 pys) in women who initiated ART from 01/2009 onward when the cervical cancer screening program and access to treatment of cervical lesions was expanded [adjusted hazard ratio (aHR) 0.42, 95% CI 0.20–0.87]. Advanced HIV/AIDS stage (4 versus 1, aHR 1.95, 95% CI 1.17–3.24) and middle age at ART initiation (36–45 versus 18–25 years, aHR 2.51, 95% CI 1.07–5.88) were risk factors for ICC. The ICC incidence rate substantially decreased with the implementation of a Pap‐based screening program and improved access to treatment of cervical lesions. However, the risk of developing ICC after ART initiation remained high. To inform and improve ICC prevention and care for HIV‐positive women in sub‐Saharan Africa, implementation and monitoring of cervical cancer screening programs are essential.

HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study

BackgroundHIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa.MethodsThe Johannesburg Cancer Case–control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing.ResultsA total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0–36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39–0.63)] and those residing in rural areas [OR 0.61(0.39–0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11–2.90)] and those interviewed in recent years [OR 4.13(2.62 – 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27–0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04–3.29)], hormonal contraceptive use [OR 1.33(1.09–1.62)], having at least a secondary education [OR:2.08(1.45–2.97)] and recent year of interview [OR 6.04(4.45–8.2)] were independently associated with previous HIV testing.ConclusionsIn a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

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 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 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 ≥700 cells/µL with those whose counts were <50 cells/µL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by ≥95% 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.

The South African National Cancer Registry: an update

We would like to take this opportunity to correct the misconception created by the News piece published in The Lancet Oncology regarding the “demise” of the South African National Cancer Registry (NCR). The NCR, a division of the National Health Laboratory Service, is the primary cancer surveillance system and largest repository of cancer data in South Africa. It was established in 1986 as a voluntary, pathologybased cancer surveillance system, and continues to operate; its database contains over 1·2 million cancer records with about 80 000 new cases added each year. The misconception about the NCR referred to above might have come about because the NCR has had diffi culties in the past due to changes in leadership, high staff turnover, and a lack of political and fi nancial prioritisation of cancer surveillance caused by competing national health priorities at the peak of the HIV epidemic. As a result of severe resource constraints, the NCR continued to obtain data but was unable to regularly produce reports. Additionally, between 2004 and 2010, some private laboratories withheld data because of concerns about voluntarily submitting confi dential patient information to the registry without the protection of government legislation. However, in 2011, Regulation 380 of the National Health Act (Act 61 of 2003) formally established the NCR as South Africa’s main cancer surveillance agency; the legislation makes reporting all confi rmed cancer diagnoses to the registry obligatory. Additionally, the Regulation mandated the NCR to implement population-based cancer registration in South Africa. With renewed political support, NCR has been revitalised. To expedite data processing, the registry has moved to electronic reporting of pathology data from laboratories. Cancer incidence reports for 2000–07 have been published online with further reports in progress. After great eff ort from NCR staff , we aim to soon report cancers within timeframes similar to those of leading international cancer registries. The NCR has developed a 10-year business plan for the implementation of both new population-based and existing pathology-based registration for the country. Fundraising activities have started, and a pilot populationbased registry is operational in one district of the country (Ekurhuleni District, Gauteng), with more to follow. In view of the concern among stakeholders about the decline in reporting from private laboratories in the past, our researchers did a thorough investigation to quantify the eff ect of withheld reports on national cancer surveillance. We found a marginal eff ect on overall reporting; NCR will submit these fi ndings for peer-reviewed publication soon. The NCR remains the main source of cancer data for South Africa, with laboratory-based reporting yielding high specifi city. With the imminent implementation of national health insurance, it is vital for the country to be able to quantify the burden of cancer for national resource planning. Increased investment in the NCR will assist the organisation to improve South African cancer surveillance.

Cancer in adolescents and young adults living with HIV.

Purpose of review Adults living with HIV have an increased risk of malignancy yet there is little data for adolescents and young adults. We reviewed recently published cancer epidemiology, treatment, and outcome data for adolescents and young adults living with HIV (AYALHIV) aged 10 to less than 25 years between 2016 and 2017. Recent findings AYALHIV are at increased risk of developing cancer compared to their uninfected peers. Kaposi sarcoma and non-Hodgkin lymphoma occur most frequently with variation by geographical region. Increased cancer risk is associated with HIV-related immunosuppression and coinfection with oncogenic viruses. Published data, particularly on posttreatment outcomes, remain limited and analyses are hampered by lack of data disaggregation by age and route of HIV transmission. Summary Although data are sparse, the increased cancer risk for AYALHIV is the cause for concern and must be modified by improving global access and uptake of antiretroviral therapy, human papilloma virus (HPV) and hepatitis B virus (HBV) vaccination, screening for hepatitis B and C infection, and optimized cancer screening programs. Education aimed at reducing traditional modifiable cancer risk factors should be embedded within multidisciplinary services for AYALHIV.