Mentored Scientist Award

Most HIV-infected patients who stop taking antiretroviral drugs experience rapid viral rebound and suffer in the longer term from the presence of more virus in blood and lower CD4+ T cell counts. HIV-1 infection generally increases T-cell metabolism, which means that cells are more active, which promotes successful viral integration and replication. Our preliminary data show that although therapeutic T cell vaccination can effectively generate cytotoxic T cells that kill HIV-infected cells, in most cases this antiviral activity is insufficient to limit viral replication.

Most HIV-infected patients who stop taking antiretroviral drugs experience rapid viral rebound and suffer in the longer term from the presence of more virus in blood and lower CD4+ T cell counts. HIV-1 infection generally increases T-cell metabolism, which means that cells are more active, which promotes successful viral integration and replication. Our preliminary data show that although therapeutic T cell vaccination can effectively generate cytotoxic T cells that kill HIV-infected cells, in most cases this antiviral activity is insufficient to limit viral replication.

Reduction of persistent HIV-infected cells in reservoir tissues is essential towards HIV cure. It is difficult to measure tissue penetration of therapeutics (antiretrovirals, ARVs, and curative agents) in many of these sites (e.g. brain, cardiac, lung tissue) due to the inability to sample these tissues in living people. Leveraging postmortem tissue banked at UCSF from deceased people with HIV (PWH), we will determine ARV penetration in these tissue reservoir sites, and determine if there is a link between ARV exposure to size the viral reservoir in each tissue.

Reduction of persistent HIV-infected cells in reservoir tissues is essential towards HIV cure. It is difficult to measure tissue penetration of therapeutics (antiretrovirals, ARVs, and curative agents) in many of these sites (e.g. brain, cardiac, lung tissue) due to the inability to sample these tissues in living people. Leveraging postmortem tissue banked at UCSF from deceased people with HIV (PWH), we will determine ARV penetration in these tissue reservoir sites, and determine if there is a link between ARV exposure to size the viral reservoir in each tissue.

Combination antiretroviral therapy (cART) for the treatment of HIV infection has been a tremendous medical success, which continues to make strides.1 cART has dramatically reduced morbidity and mortality associated with HIV infection, allowing those that are infected to live for years without progressing to AIDS. cART does not clear the infection, however, and infected people must remain on treatment indefinitely. There have been several instances of HIV cure or remission.

Combination antiretroviral therapy (cART) for the treatment of HIV infection has been a tremendous medical success, which continues to make strides.1 cART has dramatically reduced morbidity and mortality associated with HIV infection, allowing those that are infected to live for years without progressing to AIDS. cART does not clear the infection, however, and infected people must remain on treatment indefinitely. There have been several instances of HIV cure or remission.

Although significant strides have been made in controlling viral pathogenicity via. Anti-Retroviral Therapy (ART), a major barrier to curing HIV-1 infection is the transcriptionally silent, latent proviral reservoir that resides within HIV infected individuals. These stable yet extremely rare (~1 in 1 million cells) viral reservoirs are primarily thought to be harbored in quiescent, homeo-statically proliferating, resting memory CD4+ T-cells.

Although significant strides have been made in controlling viral pathogenicity via. Anti-Retroviral Therapy (ART), a major barrier to curing HIV-1 infection is the transcriptionally silent, latent proviral reservoir that resides within HIV infected individuals. These stable yet extremely rare (~1 in 1 million cells) viral reservoirs are primarily thought to be harbored in quiescent, homeo-statically proliferating, resting memory CD4+ T-cells.

Primary health care clinics in South Africa were confronting substantial population burdens of HIV and non-communicable disease (NCD) with limited resources even prior to the Covid-19 pandemic. Care outcomes and implementation of new programs vary between clinics in the same settings; qualitative research suggests that clinic factors such as leadership may play a key role in optimizing primary care.

Primary health care clinics in South Africa were confronting substantial population burdens of HIV and non-communicable disease (NCD) with limited resources even prior to the Covid-19 pandemic. Care outcomes and implementation of new programs vary between clinics in the same settings; qualitative research suggests that clinic factors such as leadership may play a key role in optimizing primary care.