Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

Dr Admire Chikandiwa

South Africa

EDCTP portfolio: Career Development Fellowships

Dr Admire Chikandiwa intends to describe the epidemiology of anogenital and oropharyngeal cancer patterns and trends in South African men (1994-2010).

The epidemiology of human papillomavirus in HIV-positive men

Globally, the incidence of human papillomavirus-associated anal and oropharyngeal cancers (OPCs) in men is increasing. Anogenital warts (AGWs) cause significant morbidity in men and result in high medical costs worldwide. Fewer data exist for men in sub-Saharan Africa, including South Africa, due to paucity of research and poor quality of cancer registries. The challenge is to quantify the burden of disease in South Africa and sub-Saharan Africa.

The challenge

There is enough data suggesting that HPV infection is a primary underlying cause of AGWs and these cancers. Available data from other settings suggests that HIV alters the susceptibility and the natural history of HPV-associated diseases, leading to higher rates of pre-cancerous lesions. Studies suggest that antiretroviral therapy (ART) increases the regression of Cervical Intraepithelial Neoplasia (CIN) lesions, indicating immune reconstitution. However, the incidences for Anal Intraepithelial Neoplasia (AIN) and oropharyngeal lesions seem to increase steadily despite ART initiation. It is therefore important to additionally understand the natural history of anogenital and oral HPV infection in HIV-positive men and the factors associated with HPV-disease progression.

Dr Chikandiwa intends to describe the epidemiology of anogenital and oropharyngeal cancer patterns and trends in men, including incidence and mortality rates and differences by ethnicity in South Africa between 1994 and 2010. Furthermore, to explore the influence of HIV status on the epidemiology of these cancers.

His second objective is to determine the prevalence of anogenital and oropharyngeal HPV infection, genotype distribution and associations with anogenital disease, according to HIV-related factors and exposure to ART. Finally, he will determine the incidence, persistence, and clearance of type-specific anogenital and oropharyngeal HPV infection and anal cytological lesions over 18 months and the effects of HIV-related factors and concomitant exposure to ART on these outcomes.

The project

Quantification of the burden of these diseases in South Africa and sub-Saharan Africa is an important first step as fewer data exist for men in South Africa due to paucity of research, poor quality of cancer registries, and high costs of screening. Further steps needed may comprise investigation of biomarkers such as HPV viral load to identify men at high risk of progression to cancer. HPV DNA testing could be used to screen for OPCs, however, the best sampling method for oropharyngeal HPV DNA infection is yet to be agreed on.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Globally, the incidence of human papillomavirus-associated anal and oropharyngeal cancers (OPCs) in men is increasing. Anogenital warts (AGWs) cause significant morbidity in men and result in high medical costs worldwide. Fewer data exist for men in sub-Saharan Africa, including South Africa, due to paucity of research and poor quality of cancer registries. The challenge is to quantify the burden of disease in South Africa and sub-Saharan Africa.

There is enough data suggesting that HPV infection is a primary underlying cause of AGWs and these cancers. Available data from other settings suggests that HIV alters the susceptibility and the natural history of HPV-associated diseases, leading to higher rates of pre-cancerous lesions. Studies suggest that antiretroviral therapy (ART) increases the regression of Cervical Intraepithelial Neoplasia (CIN) lesions, indicating immune reconstitution. However, the incidences for Anal Intraepithelial Neoplasia (AIN) and oropharyngeal lesions seem to increase steadily despite ART initiation. It is therefore important to additionally understand the natural history of anogenital and oral HPV infection in HIV-positive men and the factors associated with HPV-disease progression.

Dr Chikandiwa intends to describe the epidemiology of anogenital and oropharyngeal cancer patterns and trends in men, including incidence and mortality rates and differences by ethnicity in South Africa between 1994 and 2010. Furthermore, to explore the influence of HIV status on the epidemiology of these cancers.

His second objective is to determine the prevalence of anogenital and oropharyngeal HPV infection, genotype distribution and associations with anogenital disease, according to HIV-related factors and exposure to ART. Finally, he will determine the incidence, persistence, and clearance of type-specific anogenital and oropharyngeal HPV infection and anal cytological lesions over 18 months and the effects of HIV-related factors and concomitant exposure to ART on these outcomes.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

Quantification of the burden of these diseases in South Africa and sub-Saharan Africa is an important first step as fewer data exist for men in South Africa due to paucity of research, poor quality of cancer registries, and high costs of screening. Further steps needed may comprise investigation of biomarkers such as HPV viral load to identify men at high risk of progression to cancer. HPV DNA testing could be used to screen for OPCs, however, the best sampling method for oropharyngeal HPV DNA infection is yet to be agreed on.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M