Pilot Award

It is well known that children born to women co-infected with HIV and malaria are at increased risk of low birthweight and perinatal death. Preliminary work has shown that indoor residual spraying with insecticide, a well-known malaria control strategy, is associated with 50-71% reduction in low birthweight and 61-90% risk reduction in neonatal mortality among both HIV-infected women and HIV-uninfected women. While potentially important findings, the opportunistic before and after study design approach used is open to issues of confounding.

While highly active anti-retroviral therapy has greatly improved the lives of HIV infected individuals, current treatments are unable to completely eradicate the virus. A number of latency reversing agents, including HDAC and BET bromodain inhibitors, are unsuccessful when used in resting CD4+T cells which lack sufficient expression of transcriptional activators such as P-TEFb and NF-κB, which are also important regulators of HIV transcription. MAPK and PKC agonists are potent T cell activators, which induce expression of these transcription factors.

Incidence of anal cancer is more than eighty times higher in HIV-infected men who have sex with men (MSM) than in the HIV-uninfected population. Because the majority of these patients are diagnosed in the early stages and early anal cancer typically responds well to concurrent chemoradiation, research on long-term survivorship in this population is a growing yet unmet need. Sexual dysfunction is one of the most common and distressing consequences of anal cancer treatment.

People who inject drugs (PWID) are the most severely affected population for HIV and HCV in Iran. Moreover, Iran, straddling the world’s major supply route of heroin, has the higher per capita opioid users in the world. Combination prevention approaches a have been implemented, including medically assisted drug treatment (mainly opiate agonist therapies [OAT] including clonidine detoxification with or without methadone or buprenorphine maintenance therapy [MMT, BMT, respectively]),needle and syringe exchange, and condom distribution programs. All are provided free of charge.

HIV-1 evolved to encode an envelope protein (Env) that triggers fusion of viral and cellular membranes while minimizing the exposure of its key domains to the host immune response. Long variable domains protect HIV-1 Env from the host humoral response; however, they seem detrimental for the transmission or early expansion of HIV-1. In the scheme of opposite selective pressures exerted by the immune response and the bottleneck of transmission, V1/V2 domain of Env appears center stage.

Abstract Alcohol consumption is a critical driver of the HIV epidemic in sub-Saharan Africa. Among those with HIV, alcohol consumption has consistently been associated with reduced antiretroviral adherence crucial for treatment as prevention. Thus, reducing alcohol use among those with HIV is a high priority. Brief interventions to reduce alcohol use (ABI) have been efficacious in primary care in developed countries. However, the usefulness of ABIs depends on effective screening for unhealthy alcohol use.

Millions of HIV-infected individuals are now receiving life-saving ART, but with evidence of ongoing immune dysfunction despite treatment and the current absence of an effective cure, HIV cure has emerged as an important research strategy. This pilot non-human primate study will evaluate the tolerability and biologic effect of increasing doses of Euphorbia kansui, an inexpensive, readily available herbal supplement used in Traditional Chinese Medicine (TCM) shown to reactivate latent HIV-1 in an in vitro model.

Despite the success of highly active antiretroviral therapy (HAART), many HIV-infected patients never achieve a CD4 recovery greater than 500 cells/mm3 even after many years on treatment. Poor immune reconstitution, despite good virologic control, is associated with low baseline CD4 count, old age, and co-morbid disease. While a number of interventions have been suggested to improve immunologic outcomes for those at risk for incomplete CD4 T cell response, very few have successfully improved outcomes for patients with poor initial immune recovery.

Antiretroviral therapy (ART) has demonstrated efficacy and durability in suppressing HIV replication in infected individuals. However, ART does not achieve viral eradication due to the persistence of latently infected cells. The eradication of HIV necessitates elimination of this reservoir. Methods to reactivate HIV latently infected cells allowing direct viral cytopathic effects or immune-mediated clearance are being considered as cure strategies. However, existing latency-reversing agents exert weak effects on HIV reactivation.

The overarching goal of this cross-sectional study is to examine if co-morbid heavy alcohol use is associated with innate immune activation and expression of inflammatory genes in HIV-positive, methamphetamine-using men who have sex with men (MSM) treated with anti-retroviral therapy (ART). Chronic activation of the innate immune system and inflammation are independently linked to an excess risk of age-related morbidity and mortality in HIV.