Publications

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

Dr Derseree Archary

South Africa

EDCTP portfolio: Senior Fellowships

Dr Derseree Archary is investigating how pre-exposure prophylaxis (PrEP) to prevent HIV infection affects immune responses in women.

Understanding the impact of pre-exposure prophylaxis on immunity

PrEP, pre-emptive use of antiretroviral drugs to prevent infection, is increasingly seen as a crucial HIV prevention strategy. Although it has been shown to be safe and effective, PrEP involves the administration of powerful drugs to people who are not unwell, and its long-term impact is unclear.

In particular, it is not known how PrEP affects immune responses or the composition of the body’s microbial communities (the microbiome), which play key roles in defence against infection. This is an important question, given that PrEP may also be used in combination with HIV vaccines.

The challenge

Combined PrEP and vaccine use may be a particularly attractive combination for preventing HIV infection in women, in whom PrEP has shown mixed results. Dr Derseree Archary is therefore examining the immunological and microbiological impact of PrEP specifically in women.

In her EDCTP Senior Fellowship, Dr Archary is taking advantage of the CAPRISA 082 trial, which is following a cohort of women at risk of HIV in South Africa, some of whom will be taking PrEP. She will examine antiretroviral drug levels in blood and the genital tract of these women, as well as antibody production and immune cell characteristics before and after the initiation of PrEP. She will also explore any changes in the composition and properties of the microbiome of the genital tract. 

The project

Dr Archary’s Senior Fellowship project will generate key data on the impact of oral PrEP on immune responses and the microbiome of the female genital tract. The findings will be crucial to anticipating the possible impact of PrEP on immune responses stimulated by an HIV vaccine, of great importance when combined use of the two therapeutic strategies is being considered.

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

PrEP, pre-emptive use of antiretroviral drugs to prevent infection, is increasingly seen as a crucial HIV prevention strategy. Although it has been shown to be safe and effective, PrEP involves the administration of powerful drugs to people who are not unwell, and its long-term impact is unclear.

In particular, it is not known how PrEP affects immune responses or the composition of the body’s microbial communities (the microbiome), which play key roles in defence against infection. This is an important question, given that PrEP may also be used in combination with HIV vaccines.

Combined PrEP and vaccine use may be a particularly attractive combination for preventing HIV infection in women, in whom PrEP has shown mixed results. Dr Derseree Archary is therefore examining the immunological and microbiological impact of PrEP specifically in women.

In her EDCTP Senior Fellowship, Dr Archary is taking advantage of the CAPRISA 082 trial, which is following a cohort of women at risk of HIV in South Africa, some of whom will be taking PrEP. She will examine antiretroviral drug levels in blood and the genital tract of these women, as well as antibody production and immune cell characteristics before and after the initiation of PrEP. She will also explore any changes in the composition and properties of the microbiome of the genital tract. 

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.

Dr Archary’s Senior Fellowship project will generate key data on the impact of oral PrEP on immune responses and the microbiome of the female genital tract. The findings will be crucial to anticipating the possible impact of PrEP on immune responses stimulated by an HIV vaccine, of great importance when combined use of the two therapeutic strategies is being considered.

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