Research | Basic | HIV Cure Research
Advancing Scientific Understanding Toward an HIV Cure
At the Rakai Health Sciences Program (RHSP), our HIV Cure Research initiatives aim to advance scientific understanding of HIV persistence and explore innovative approaches that could contribute to the development of an HIV cure.
Although antiretroviral therapy (ART) effectively suppresses HIV replication, the virus can remain hidden in certain immune cells, forming what is known as the latent HIV reservoir. These reservoirs present one of the greatest challenges to achieving a cure, as the virus can persist even when it is undetectable in the blood.
Through collaborative research, advanced laboratory techniques and long-term studies involving people living with HIV in Uganda, RHSP investigates the size and characteristics of viral reservoirs, HIV integration sites, viral latency, immune responses, and the potential influence of pregnancy on HIV persistence.
Our research contributes valuable evidence from African populations to global HIV cure efforts, supporting the development of future strategies that are scientifically informed and inclusive.
Ongoing Research
Quantitative Measurement and Correlates of the Latent HIV Reservoir in Virally Suppressed Ugandans
Despite prolonged antiretroviral therapy (ART), HIV-1 persists as transcriptionally inactive proviruses in resting memory CD4 T cells. This latent reservoir has a long half-life and remains a major barrier to achieving an HIV cure through ART alone.
The LEIDOS study seeks to measure and quantify the systemic latent HIV reservoir among Ugandans living with HIV, examine its rate of decay over time during ART, and explore novel approaches toward reservoir reactivation and eradication.
The study examines the influence of endemic infectious diseases, immune activation, nadir CD4 count, duration of exposure to viraemia, and length of suppressive treatment on latent HIV reservoir size.
Study Objectives
- Examine and measure latent HIV reservoir levels at baseline and annually thereafter for a total follow-up period of 20 years.
- Determine the role of endemic infectious diseases, nadir CD4 count, exposure to viraemia and duration of suppressive treatment in reservoir size.
- Explore immune activation in relation to reservoir size and decay rate.
- Evaluate potential latency reversal agents in vitro.
Study Design
This longitudinal descriptive study involves 90 virally suppressed men and women recruited through the RHSP Center for Excellence in Research. Participants undergo annual follow-up visits involving study questions and blood sample collection. Follow-up, initially conducted over 15 years, is being extended to 20 years.
How Pregnancy Affects the Hidden HIV Virus: A Study of Women in Uganda
Why This Study Matters
More than half of all people living with HIV worldwide are women, yet pregnant women are rarely included in HIV cure research.
Although antiretroviral therapy (ART) effectively controls HIV, it cannot completely eliminate the virus. A small amount of HIV remains hidden in infected cells, forming what is known as the latent HIV reservoir. This hidden reservoir is a major barrier to achieving an HIV cure because it cannot be eliminated by ART alone.
Early evidence suggests that estrogen, a hormone that increases significantly during pregnancy, may influence the size of the HIV reservoir. The LIFESPAN Study seeks to understand how the reservoir changes during pregnancy and how these changes could inform the development of future HIV cure strategies.
What Are We Doing?
The study is enrolling 250 women aged 18–40 years living with well-controlled HIV in the Rakai–Masaka region of Uganda.
At enrolment, participants must be receiving HIV treatment, must not be pregnant, and must be open to becoming pregnant.
A blood sample is collected at enrolment to measure HIV reservoir size before pregnancy. Participants are then contacted monthly by telephone for up to three years.
Women who become pregnant provide additional blood samples during pregnancy and 6–9 months after delivery. Women who do not become pregnant complete their final study visit between 18 and 36 months after enrolment.
Researchers use these samples to measure hidden HIV reservoirs and monitor immune changes, comparing women who become pregnant with those who do not.
What Makes This Study Unique?
The LIFESPAN Study is designed specifically to investigate how pregnancy affects the hidden HIV reservoir by following women from before conception, through pregnancy, and after delivery.
The study focuses on Ugandan women, a population that has been underrepresented in HIV cure research despite the significant burden of HIV among women in sub-Saharan Africa.
The research team has also developed laboratory tests tailored to HIV subtypes found in Uganda, enabling more accurate measurement of hidden HIV reservoirs.
Early Insights and Expected Impact
The study's laboratory tools have demonstrated the ability to quantify hidden HIV reservoirs in samples from Uganda.
Researchers expect to identify differences in reservoir size between women who become pregnant and those who do not.
The findings are expected to generate evidence that can support the inclusion of pregnant women in future HIV cure trials and help ensure that potential HIV cure strategies address the needs of women living with HIV.
The study may also provide insights into whether pregnancy represents a potential window for interventions targeting the hidden HIV reservoir.
About the REACH Study
REACH (Research Enterprise to Advance a Cure for HIV) is a National Institutes of Health (NIH) Martin Delaney-funded research consortium that brings together basic, applied, and clinical researchers studying HIV persistence and developing potential curative strategies.
The collaboration seeks to advance scientific understanding of HIV reservoirs and support multidisciplinary research into approaches that could contribute to an HIV cure.
RHSP's Contribution to REACH
The Rakai Health Sciences Program (RHSP) maintains an HIV cure research cohort of 90 people living with HIV, contributing to a greater understanding of HIV cure research and viral persistence from an African perspective.
Through this cohort, initially funded by the National Institute of Allergy and Infectious Diseases (NIAID), researchers have examined baseline HIV reservoir size and documented differences between Ugandan men and women and populations in the United States.
Research Progress and Findings
The study has described baseline measurements of HIV reservoir size among participants in Uganda.
Researchers have also documented transient declines in the size of replication-competent HIV reservoirs following the rollout of dolutegravir (DTG)-based antiretroviral treatment.
These observations contribute to ongoing investigations into HIV reservoir persistence and changes during treatment.
Ongoing Research Activities
Further research is underway to better understand the mechanisms responsible for HIV reservoir persistence, how reservoirs change over time, and potential approaches toward viral eradication.
This work includes the transfer of advanced laboratory technologies to the RHSP research setting, particularly:
- Droplet Digital Polymerase Chain Reaction (ddPCR): A laboratory platform being transferred to support HIV reservoir research.
- Intact Proviral DNA Assay (IPDA): An assay used in ongoing investigations of HIV reservoir persistence.
These activities contribute to RHSP's capacity to conduct HIV cure research and generate scientific evidence from African populations.