Current HIV/AIDS Reports

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low- and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (N = 97,657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RR = 1.02, 95 % CI 0.99 to 1.04), virologic suppression (RR = 1.00, 95 % CI 0.98 to 1.03), and all-cause mortality (RR = 0.93, 95 % CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RR = 1.03, 95 % CI 1.01 to 1.06) and cohort studies (RR = 1.09, 95 % CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective.

In this review, we examine the intersection of the HIV and COVID-19 epidemics with focus on COVID-19-related health outcomes and risk factors for SARS-CoV-2 among people living with HIV (PLWH). Evidence to date do not suggest a higher incidence of SARS-CoV-2 infection among PLWH compared to the general population, although—once exposed—PLWH are at greater risk of severe COVID-19 outcomes. Key risk factors for severe COVID-19 include non-HIV comorbidities known to be associated with severe disease, as well as HIV-specific risk factors such as low CD4 + T-cell count, unsuppressed viral load, and tuberculosis co-infection. The disproportionate impact of the SARS-CoV-2 pandemic among Black, Latinx, and Native American/Alaskan Native PLWH could worsen pre-existing disparities in health outcomes among PLWH. Data on SARS-CoV-2 vaccine protection among PLWH needs additional study, although some studies suggest decreased humoral responses among those with low CD4 + T-cell counts, while there is a signal of increased vaccine breakthrough rates among PLWH in two large observational cohorts. Data on post-acute sequelae of SARS-CoV-2 (PASC) among PLWH is also limited. PLWH do not have a higher susceptibility to SARS-CoV-2, but once exposed, they are at higher risk of severe COVID-19 outcomes. Additional resources will need to be dedicated to the development of interventions to improve health outcomes and address disparities among PLWH impacted by the COVID-19 pandemic.

The adult human brain harbors billions of microglia and other myeloid and lymphoid cells highly susceptible to HIV infection and retroviral insertion into the nuclear DNA. HIV infection of the brain is important because the brain is a potentially large reservoir site that may be a barrier to HIV cure strategies and because infection can lead to the development of HIV-associated neurocognitive disorder. To better understand both the central nervous system (CNS) reservoir and how it can cause neurologic dysfunction, novel genomic, epigenomic, transcriptomic, and proteomic approaches need to be employed. Several characteristics of the reservoir are important to learn, including where the virus integrates, whether integrated proviruses are intact or defective, whether integrated proviruses can be reactivated from a latent state to seed ongoing infection, and how this all impacts brain function. Here, we discuss similarities and differences of viral integration sites between brain and blood and discuss evidence for and against the hypothesis that in the absence of susceptible T-lymphocytes in the periphery, the virus housing in the infected brain is not able to sustain a systemic infection. Moreover, microglia from HIV + brains across a wide range of disease severity appear to share one type of common alteration, which is defined by downregulated expression, and repressive chromosomal compartmentalization, for microglial genes regulating synaptic connectivity. Therefore, viral infection of the brain, including in immunocompetent cases with near-normal levels of CD4 blood lymphocytes, could be associated with an early disruption in microglia-dependent neuronal support functions, contributing to cognitive and neurological deficits in people living with HIV.

Increased access to testing and treatment means HIV can be managed as a chronic illness, though successful management requires continued engagement with the health care system. Most of the global HIV burden is in sub-Saharan Africa where rates of new infections are consistently higher in women versus men. Pregnancy is often the point at which an HIV diagnosis is made. While preventing mother to child transmission (PMTCT) interventions significantly reduce the rate of vertical transmission of HIV, women must administer ARVs to their infants, adhere to breastfeeding recommendations, and test their infants for HIV after childbirth. Some women will be expected to remain on the ARVs initiated during pregnancy, while others are expected to engage in routine testing so treatment can be reinitiated when appropriate. The postpartum period presents many barriers to sustained treatment adherence and engagement in care. While some studies have examined adherence to postpartum PMTCT guidelines, few have focused on continued engagement in care by the mother, and very few examine adherence beyond the 6-week postpartum visit. Here, we attempt to identify gaps in the research literature and make recommendations on how to address barriers to ongoing postpartum HIV care.

Antiretroviral treatment (ART) can dramatically reduce the risk of HIV transmission, but the feasibility of scaling up HIV testing, linkage and treatment to very high population levels, and its impact on population HIV incidence, were unknown. We review key findings from a community-randomized trial in which we evaluated the impact of “universal test and treat” (UTT) on population HIV incidence in Botswana, a resource-constrained country with both high HIV prevalence and high ART coverage before study inception. We conducted a community-randomized trial (the “Ya Tsie” trial or Botswana Combination Prevention Project (BCPP)) in 30 villages in Botswana from 2013 to 2018, with the goal of determining whether a combination of prevention interventions—with a focus on universal HIV testing and treatment—would reduce population-level HIV incidence. The intervention included universal HIV testing (home-based and mobile), active linkage to HIV care and treatment with patient tracing for persons not linking, universal ART coverage, rapid ART start (at the first clinic visit), and enhanced male circumcision services. Botswana had very high HIV diagnosis, treatment, and viral suppression levels (approaching the UNAIDS “90-90-90” targets) prior to intervention roll-out. By study end, we were able to exceed the overall 95-95-95 coverage target of 86%: an estimated 88% of all persons living with HIV were on ART and had viral suppression in the Ya Tsie intervention arm. In addition, annual HIV incidence was 30% lower in the intervention arm as compared with the control arm over a 29-month follow-up period. With universal HIV testing and relatively simple linkage activities, it was possible to achieve one of the highest reported population levels of HIV diagnosis, linkage to care, and viral suppression globally and to reduce population HIV incidence by about one-third over a short period of time (< 3 years). We were able to significantly increase population viral suppression and to decrease HIV incidence even in a resource-constrained setting with pre-existing very high testing and treatment coverage. Universal community-based HIV testing and tracing of individuals through the HIV care cascade were key intervention components.

In the current era of combination antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected individuals are living longer and healthier lives. Nevertheless, HIV-infected persons are at greater risk for age-related disorders, which have been linked to residual immune dysfunction and inflammation. HIV-infected individuals are almost universally co-infected with cytomegalovirus (CMV) and both viruses are associated with inflammation-related morbidities. Therefore, a detailed investigation of the relationship between CMV and aging-related morbidities emerging during chronic HIV infection is warranted. Here, we review the literature on how CMV co-infection affects HIV infection and host immunity and we discuss the gaps in our knowledge that need elucidation.

Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam.

HIV is an independent risk factor for heart failure (HF). Cardiac imaging studies in people with HIV (PWH) have identified myocardial pathologies, namely fibrosis and steatosis, that likely contribute to the higher risk of HF. In this review, we survey existing epidemiological, clinical, and mechanistic literature to identify potential pathways that may contribute to the burden of myocardial fibrosis and steatosis among PWH. Multiple cohort studies over the past 20 years have demonstrated a roughly 2-fold higher risk of incident HF in PWH, as well as a disproportionate burden of myocardial fibrosis and steatosis in PWH without HF. Both myocardial fibrosis and steatosis are known contributors to HF in adults without HIV. Pathways involving the NLRP3 inflammasome, TGF-β1, and adipocyte dysfunction are known to play a crucial role in the development of myocardial fibrosis and steatosis. Upregulation of these pathways in HIV due to direct effects of viral proteins, persistent immune dysregulation, gut epithelial breakdown and dysbiosis, and toxicities from antiretroviral therapy may contribute to myocardial dysfunction in HIV. Understanding these pathways may lead to more precise diagnostic and therapeutic targets to curb HF in PWH. During the past three decades, observational and mechanistic studies have provided important insights into risk factors and pathways that may contribute to the increased HF risk in PWH. Future work is needed to characterize these pathways more precisely in mechanistic studies of PWH, with the goal of ultimately deriving valuable targets for prevention, early diagnosis, and treatment of HF in PWH.