Research Programs (by Faculty Member)

Molecular Epidemiology of Antimalarial Resistance

Our focus is on understanding the emergence and evolution of antimalarial drug resistance in sub-Saharan Africa. Using molecular and parasitological approaches, we characterize changes in Plasmodium falciparum populations overtime with the goal of understanding the factors that favor emerging resistance, identifying novel markers of resistance, and characterizing mechanisms of action and resistance.

Study on the Consequences of the Protease-Inhibitor Era (SCOPE)

The SCOPE program is a long-term research initiative focused on understanding the clinical, immunological, and virological outcomes of HIV in the era of effective antiretroviral therapy (ART). At the center of the program is a large prospective cohort of over 2000 people with and without HIV.  Clinical data and biologic specimens are collected over years to decades in a variety of populations, including individuals with who started ART in acute infection, those who control in the absence of therapy, those who control after ART or interventions. The extended SCOPE team investigates critical topics such as immune activation, inflammation, viral persistence, and the long-term side effects of ART. Over 20 investigator-initiated clinical trials have been conducted within the SCOPE program. By combining clinical data, advanced laboratory techniques, and participant-reported outcomes, SCOPE seeks to improve the understanding of HIV pathogenesis and treatment, while contributing to strategies for improving quality of life and developing a cure for HIV infection.

Malaria Research Collaboration in Uganda

Our malaria research group has been working with the Infectious Diseases Research Collaboration in Uganda since 1998. Areas of interest include clinical trials for the treatment and prevention of malaria, antimalarial drug resistance, antimalarial drug discovery, pharmacokinetics and pharmacodynamics of antimalarial drugs, malaria in pregnancy, molecular epidemiology, naturally acquired immunity to malaria, and public health surveillance. Since 2010 we have been a member of the International Centers of Excellence for Malaria Research (ICEMR) program, a global network of independent research centers in malaria-endemic settings established by the NIH.

Interventions to Reduce Alcohol Use by Persons with HIV

Alcohol use above recommended levels, called unhealthy alcohol use, substantially worsens HIV-related morbidity but is treatable. It is common (22-30% prevalent) among persons with living with HIV (PLWH), associated with poor HIV outcomes, and increases the risk for co-morbidities such as tuberculosis and noncommunicable diseases (NCDs) that increase with age. Thus, there is an urgent need to reduce unhealthy alcohol use in PLWH, especially in Uganda, a country with high prevalence of HIV (5.8%), unhealthy alcohol use, and co-morbidities. The goals of our work are to identify, adapt, and test low-cost effective interventions to help PWLH reduce their alcohol use and improve their HIV and related conditions. ​​​​​​

Alcohol Biomarkers

Research to reduce the harm of alcohol use that relies on self-report is often inaccurate due to recall bias and/or social desirability bias, and inconsistent across studies. Inaccurate reporting can lead to spurious or obscured results, especially in research among persons living with HIV (PLWH). Objective biomarkers that can detect alcohol metabolites offer promise to improve upon self-report and add measurement consistency. The leading alcohol biomarker is phosphatidylethanol (PEth), which is detected in whole blood or dried blood spots, is highly sensitive and specific for unhealthy alcohol use, and has good correlations with the total amount of alcohol consumed over the past 2-4 weeks. Our research leverages PEth measured in multiple alcohol/HIV studies to examine the relationship of PEth-measured alcohol use with HIV virologic failure and mortality risk, and to determine the efficacy of alcohol/HIV interventions among PLWH. We are also examining the tools of machine learning to determine whether a combination of routine laboratory tests can serve as a low-cost alternative to PEth, to make objective testing more available in low-resource settings.

Alcohol and HIV and TB Co-infection

The risk for tuberculosis (TB), is the leading cause of death among persons living with HIV (PLWH), is 3-fold for those engaging in heavy alcohol use compared to those who abstain, and TB treatment outcomes are poorer. Our research aims to determine the risk of acquiring TB infection and of incident active TB disease among PLWH with heavy alcohol use after receipt of TB preventative therapy (TPT) in PLWH in high HIV/TB settings, adjusting for important cofactors such as smoking and crowding. This work will inform interventions to reduce the risk for acquiring new TB infection and to reduce the risk of active TB.

SEARCH Collaboration

SEARCH is a multi-disciplinary, international consortium that aims to accelerate the path to elimination of HIV incident infections through innovative combination strategies for HIV prevention and treatment that are effective, efficient, and scalable. We are testing new approaches and products that reduce preventable infections and deaths using a community precision health model that reaches into the community and incorporates data systems and analytics. Building on early studies of a patient-centered, multi-disease HIV test-and-treat model, we recently demonstrated that offering a choice for HIV prevention products, including injectable long-acting agents, can dramatically reduce new HIV infections. We have also shown that leveraging the infrastructure of HIV health delivery to other diseases such as hypertension can improve cardiovascular outcomes at a population level. Our goal is to provide the evidence for new strategies to optimize health outcomes for highest burden diseases on the path to ending AIDS.

Pulmonary Research

The lungs are a major target of HIV and HIV-associated pulmonary diseases are leading causes of both hospitalization and death. HIV-associated opportunistic pneumonias, including tuberculosis (TB), continue to be among the leading opportunistic infections in persons with HIV infection worldwide. As the HIV population ages in San Francisco, the US, and throughout the world, age-associated pulmonary diseases such as chronic obstructive pulmonary disease (COPD) are increasing. Our goal is to improve the diagnosis and clinical management of HIV-associated opportunistic pneumonias and COPD both in the US and throughout the world. We also strive to understand the complex relationships between chronic immune activation and inflammation, aging, and the microbial communities that reside in the lungs of persons with HIV and the development and progression of HIV-associated COPD and lung function abnormalities. In particular, we are investigating individuals with a reduced diffusion capacity for carbon monoxide (DLco) but with normal spirometry, a lung function pattern that we have called, iso↓DLco.

Pulmonary/Tuberculosis

Tuberculosis (TB) has a devastating impact in low- and middle-income countries (LMICs) and in persons with HIV (PWH). A substantial proportion of the estimated 155 million TB survivors have persistent respiratory complaints, abnormal lung function, and/or chest X-ray abnormalities, significantly higher than those who never had TB, highlighting the large burden of post-TB lung disease (PTLD). The burden of PTLD is magnified in PWH and LMICs, where most TB cases occur and where resources for diagnosing and managing PTLD may be limited. PTLD is also morbid, underscoring that individuals may survive and be considered “cured” after successful TB treatment, but many will continue to experience discomfort and disability long after treatment ends. Our goals are to determine the most effective tests for diagnosing and monitoring PTLD to guide clinical care, identify risk factors for PTLD to develop targeted interventions and inform public policy, and understand mechanisms underlying PTLD to facilitate the development of therapies to prevent or mitigate this condition.

TB Diagnostic and Implementation Research in Zambia

Our work applies implementation science methods to improve individual- and population-level outcomes across the TB and HIV care cascades through person-centered and equity-focused approaches. Our research particularly focuses on (1) the development and implementation of novel TB diagnosis and case-finding tools and strategies, and (2) implementation readiness in high-burden countries for new TB vaccines targeting adults and adolescents.

Host Genomics and Infectious Diseases Translational Research

The lab investigates the role of host genetics and immunology in infectious disease pathogenesis and persistence using high-throughput genetic sequencing and immunologic methods combined with discovery-based multiomic analytic approaches. Our work leverages patient samples from observational and clinical trials to identify novel targets for the treatment of infectious diseases, including HIV and SARS-CoV-2. Our research includes studying host-specific drug responses to interventions using pharmacokinetic/pharmacodynamic modeling, as well as identifying genetic and immunologic signatures that predict unique clinical phenotypes. The ultimate goal of our research is to improve clinical outcomes for human infectious diseases, such as achieving ART-free remission in people with HIV.

The San Francisco Infectious Diseases Research Center (SF IDRC)

The SF IDRC is a multi-purpose research program implementing NIH- and pharma-funded clinical trials. Our center conducts cutting-edge clinical trials to improve the lives of people living with HIV and other infectious. Our mission is to investigate the most effective strategies to treat, prevent, and cure infectious diseases, including HIV, HIV-related complications, viral hepatitis, sexually transmitted infections, and emerging infectious diseases, including MPOX and novel respiratory pathogens. Based in the new UCSF Pride Hall building on the Zuckerberg San Francisco General campus, SF IDRC is home to the UCSF NIH-funded UCSF ACTG (Advancing Clinical Trials Globally for HIV/AIDS and Other Infections) as well as other NIH-funded networks, investigator-initiated studies, and industry partnerships. As part of the NIH-funded SFBay Clinical Trials Unit, our ACTG site partners with BridgeHIV, which conducts HIV and STI prevention studies.

Long-term Impact of Infection With Novel Coronavirus (LIINC)

The LIINC study is a research initiative aimed at understanding the long-term effects of COVID-19. LIINC investigates the biological, immunological, and clinical outcomes associated with COVID-19 to provide insights into long COVID and other post-acute sequelae of SARS-CoV-2 infection. The study enrolls individuals who have recovered from COVID-19 and conducts regular assessments, including blood tests, symptom tracking, and clinical evaluations. It focuses on various aspects such as immune system changes, organ function, and the persistence of symptoms like fatigue, brain fog, and respiratory issues. LIINC participants can opt in to more intensive studies including biopsies which support the UCSF Long COVID Tissue Bank (GI tract, lymph node, bone marrow, endometrium, spinal fluid), imaging (PET scans), and clinical trials. By integrating diverse scientific approaches, LIINC aims to inform the development of treatments, public health strategies, and improved care for those experiencing prolonged symptoms, contributing to a deeper understanding of the pandemic’s long-term health impacts.

Researching COVID to Enhance Recovery (RECOVER)

The UCSF RECOVER study is part of a national research initiative aimed at understanding the long-term effects of COVID-19, including “long COVID.” It seeks to identify the biological, clinical, and social factors contributing to prolonged symptoms and health challenges after acute infection. By studying a diverse group of participants, the study examines the persistence of symptoms like fatigue, brain fog, and respiratory issues, along with immune system changes and organ damage. UCSF’s role in RECOVER involves detailed assessments, including symptom tracking, biomarker analysis, and imaging studies, to uncover mechanisms driving long COVID. Through collaboration with other institutions, RECOVER contributes to a nationwide effort to address the pandemic's long-term health impacts and improve outcomes for affected individuals. RECOVER participants are given the opportunity to also participate in our UCSF-based long COVID research program, LIINC, which is pursuing different but related questions.

The Impact of Social and Structural Factors on Comorbidities and Population Health

The research group investigates how clinical, biological, and behavioral factors converge to influence the health of individuals and populations. We investigate how social and structural factors like unstable housing and food insecurity, together with addiction and mental health conditions, influence HIV outcomes and cardiovascular comorbidities. Our work links research participation with health records to understand long-term influences and identify novel points of intervention. We seek to inform the adaptation of risk assessment tools and the development of clinical interventions that are relevant to the patients they serve. This includes identifying opportunities for simplification and alternative options that meet the needs of people who are not well-engaged in traditional healthcare. Our goal is to maximize the potential of modern medicine for everyone.

Antimalarial Drugs and Resistance

We conduct laboratory, clinical, and translational research on malaria. Key focuses include translational studies of antimalarial drug activity and resistance, clinical trials to test regimens for the treatment and prevention of malaria, studies of the pharmacokinetics and pharmacodynamics of antimalarial drugs, and studies to identify novel antimalarial agents and to determine their mechanisms of action. Primary research sites are at UCSF and in Uganda and Burkina Faso.

Implementation of HIV Prevention and Treatment

Our group focuses on implementation science approaches to support pre-exposure prophylaxis (PrEP) implementation, PrEP/HIV ART adherence, and PrEP persistence/HIV retention in care. A key tool we are using is a point-of-care (POC) urine tenofovir test, which provides real-time adherence information to clinicians to guide adherence interventions. Our randomized clinical trial, PrEP2-BAY, uses motivational interviewing counseling, targeted by the urine POC test, to support PrEP adherence among young sexual minority men. Additionally, we lead the American Remote Contact HIV Epidemiology Study (ARCHES), a large, limited-interaction targeted epidemiology cohort of people living with HIV, examining the HIV care cascade and antiretroviral therapy adherence over three years, with a focus on the impact of stimulant use on adherence and systemic inflammation. Finally, we are leading a directly observed therapy randomized clinical trial to establish adherence benchmarks for doxycycline when used as sexually transmitted infection post-exposure prophylaxis (Doxy-PEP), to support interpretation of the relationship between medication adherence and efficacy in clinical trials.