HIV-specific T cell responses reflect substantive in vivo interactions with antigen despite long-term therapy.

Antiretroviral therapies (ARTs) abrogate HIV replication; however, infection persists as long-lived reservoirs of infected cells with integrated proviruses, which reseed replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in reducing viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle: by querying the dynamics of HIV-specific T cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. In longitudinal assessments, we show that the rates of change in persisting HIV Nef-specific responses, but not responses to other HIV gene products, were associated with residual frequencies of infected cells. These Nef-specific responses were highly stable over time and disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV antigens. These results indicate substantial visibility of the HIV-infected cells to T cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing infection.

Fear of birth defects is a major barrier to soil-transmitted helminth treatment (STH) for pregnant women in the Philippines.

The World Health Organization recommends anthelminthic treatment for pregnant women after the first trimester in soil-transmitted helminth (STH) endemic regions to prevent adverse maternal-fetal consequences. Although studies have shown the high prevalence of infection in the Philippines, no research has evaluated deworming practices. We hypothesized that pregnant women are not receiving deworming treatment and we aimed to identify barriers to World Health Organization guideline implementation. We conducted key informant interviews with local Department of Health (DOH) administrators, focus group discussions with nurses, midwives, and health care workers, and knowledge, attitudes, and practices surveys with women of reproductive age to elicit perspectives about deworming during pregnancy. Key informant interviews revealed that healthcare workers were not deworming pregnant women due to inadequate drug supply, infrastructure and personnel as well as fear of teratogenicity. Focus group discussions showed that healthcare workers similarly had not implemented guidelines due to infrastructure challenges and concerns for fetal malformations. The majority of local women believed that STH treatment causes side effects (74.8%) as well as maternal harm (67.3%) and fetal harm (77.9%). Women who were willing to take anthelminthics while pregnant had significantly greater knowledge as demonstrated by higher Treatment Scores (mean rank 146.92 versus 103.1, z = -4.40, p<0.001) and higher Birth Defect Scores (mean rank 128.09 versus 108.65, z = -2.43, p = 0.015). This study concludes that World Health Organization guidelines are not being implemented in the Philippines. Infrastructure, specific protocols, and education for providers and patients regarding anthelminthic treatment are necessary for the successful prevention of STH morbidity and mortality among pregnant women.