Explore the vast range of titles available.

A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection. The durability of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. Lessons from seasonal coronavirus infections in humans show that reinfections can occur within 12 months of initial infection, coupled with changes in levels of virus-specific antibodies.

Despite a fair amount of progress on understanding human immunodeficiency virus (HIV) epidemiology globally, the Middle East and North Africa (MENA) region is the only region where knowledge of the epidemic continues to be very limited, and subject to much controversy. It has been more than 25 years since the discovery of HIV, but no scientific study has provided a comprehensive data-driven synthesis of HIV/AIDS (acquired immunodeficiency syndrome) infectious spread in this region. The current report provides the first comprehensive scientific assessment and data-driven epidemiological synthesis of HIV spread in MENA since the beginning of the epidemic. It is based on a literature review and analysis of thousands of widely unrecognized publications, reports, and data sources extracted from scientific literature or collected from sources at the local, national, and regional levels. The recommendations provided here focus on key strategies related to the scope of this report and its emphasis on understanding HIV epidemiology in MENA as a whole. The recommendations are based on identifying the status of the HIV epidemic in MENA, through this synthesis, as a low HIV prevalence setting with rising concentrated epidemics among priority populations. General directions for prevention interventions as warranted by the outcome of this synthesis are also discussed briefly, but are not delineated because they are beyond the scope of this report. This report was not intended to provide intervention recommendations for each MENA country.

Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate—adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.

Men who have sex with Men (MSM) are currently at marked risk for HIV infection in Low- and Middle-Income Countries (LMICs) in Asia, Africa, Latin America and the Caribbean, and in Eastern Europe and Central Asia. Estimates of HIV prevalence rates have been consistently higher among MSM than for the general population of reproductive-age men virtually wherever MSM have been well studied. Although scarce, HIV incidence data support findings of high acquisition and transmission risks among MSM in multiple contexts, cultural settings, and economic levels. Research among MSM in LMICs has been limited by the criminalization and social stigmatization of these behaviors, the safety considerations for study participants, the hidden nature of these populations, and a lack of targeted funding. Available evidence from these countries suggests that structural risks social, economic, political, or legal factors in addition to individual-level risk factors are likely to play important roles in shaping HIV risks and treatment and care options for these men. Services and resources for populations of MSM remain markedly low in many settings. They have limited coverage and access to HIV/AIDS prevention, treatment, and care services with some estimates suggesting that fewer than one in ten MSM worldwide have access to the most basic package of preventive interventions.

Women in sub-Saharan Africa are disproportionately affected by the HIV epidemic. Young women are twice as likely to be living with HIV as men of the same age and account for 64% of new HIV infections among young people. Many studies suggest that financial needs, alongside biological susceptibility, are a leading cause of the gender disparity in HIV acquisition. New robust evidence suggests women adopt risky sexual behaviours to cope with economic shocks, the sudden decreases in household's income or consumption power, enhancing our understanding of the link between poverty and HIV. We investigated if health insurance protects against economic shocks, reducing the need for vulnerable women to engage in risky sexual behaviours and reducing HIV and sexually transmitted infection (STI) incidence. We conducted a randomised controlled trial to test the effectiveness of a formal shock coping strategy to prevent HIV among women at high risk of HIV (registration number: ISRCTN 22516548). Between June and August 2021, we recruited 1,508 adolescent girls and women over age 15 years who were involved in transactional sex (n = 753) or commercial sex (n = 755), using snowball sampling. Participants were randomly assigned (1:1) to receive free health insurance for themselves and their economic dependents for 12 months either at the beginning of the study (intervention; n = 579; commercial sex n = 289, transactional sex n = 290) from November 2021 or at the end of the study 12 months later (control; n = 568; commercial sex n = 290, transactional sex n = 278). We collected data on socioeconomic characteristics of participants. Primary outcomes included incidence of HIV and STIs and were measured at baseline, 6 months after randomisation, and 12 months after randomisation. We found that study participants who engaged in transactional sex and were assigned to the intervention group were less likely to become infected with HIV post-intervention (combined result of 6 months post-intervention or 12 months post-intervention, depending on the follow-up data available; odds ratio (OR) = 0.109 (95% confidence interval (CI) [0.014, 0.870]); p = 0.036). There was no evidence of a reduction in HIV incidence among women and girls involved in commercial sex. There was also no effect on STI acquisition among both strata of high-risk sexual activity. The main limitations of this study were the challenges of collecting reliable STI incidence data and the low incidence of HIV in women and girls involved in commercial sex, which might have prevented detection of study effects. The study provides to our knowledge the first evidence of the effectiveness of a formal shock coping strategy for HIV prevention among women who engage in transactional sex in Africa, reinforcing the importance of structural interventions to prevent HIV. The trial was registered with the ISRCTN Registry: ISRCTN 22516548. Registered on 31 July 2021.

The landmark HIV Prevention Trials Network (HPTN) 052 trial in HIV-discordant couples demonstrated unequivocally that treatment with antiretroviral therapy (ART) substantially lowers the probability of HIV transmission to the HIV-uninfected partner. However, it has been vigorously debated whether substantial population-level reductions in the rate of new HIV infections could be achieved in \"real-world\" sub-Saharan African settings where stable, cohabiting couples are often not the norm and where considerable operational challenges exist to the successful and sustainable delivery of treatment and care to large numbers of patients. We used data from one of Africa's largest population-based prospective cohort studies (in rural KwaZulu-Natal, South Africa) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline, observing individual HIV seroconversions over the period 2004 to 2011. Holding other key HIV risk factors constant, individual HIV acquisition risk declined significantly with increasing ART coverage in the surrounding local community. For example, an HIV-uninfected individual living in a community with high ART coverage (30 to 40% of all HIV-infected individuals on ART) was 38% less likely to acquire HIV than someone living in a community where ART coverage was low (<10% of all HIV-infected individuals on ART).

Antiretroviral therapy has largely transformed HIV infection into a chronic disease condition. As such, physicians and other providers caring for individuals living with HIV infection need to be aware of the potential cardiovascular complications of HIV infection and the nuances of how HIV infection increases the risk of cardiovascular diseases, including acute myocardial infarction, stroke, peripheral artery disease, heart failure and sudden cardiac death, as well as how to select available therapies to reduce this risk. In this Review, we discuss the epidemiology and clinical features of cardiovascular disease, with a focus on coronary heart disease, in the setting of HIV infection, which includes a substantially increased risk of myocardial infarction even when the HIV infection is well controlled. We also discuss the mechanisms underlying HIV-associated atherosclerotic cardiovascular disease, such as the high rates of traditional cardiovascular risk factors in patients with HIV infection and HIV-related factors, including the use of antiretroviral therapy and chronic inflammation in the setting of effectively treated HIV infection. Finally, we highlight available therapeutic strategies, as well as approaches under investigation, to reduce the risk of cardiovascular disease and lower inflammation in patients with HIV infection.Antiretroviral therapy has transformed HIV infection into a chronic disease, and cardiovascular diseases are an important health concern in this setting. This Review discusses the clinical features of cardiovascular disease in patients with HIV infection, including the mechanisms underlying HIV-associated atherosclerosis and approaches to reduce the cardiovascular risk.

A phase I study of passive immunization with a CD4 binding-site-directed broadly neutralizing antibody shows that it transiently reduces HIV-1 viral loads in humans. Anti-HIV antibody shows promise The passive administration of broadly neutralizing antibodies (bNAbs) to HIV has been effective against HIV-1 infection in humanized mice and macaque models of HIV-1 infection. It has been suggested that bNAbs, administered passively or by viral vectors, may be effective for prevention and immunotherapy in humans. The safety and efficacy of the approach had not been tested in humans previously but here Michel Nussenzweig and colleagues report the results of a phase I study of passive immunization with neutralizing antibodies directed at CD4 binding sites, and show that the treatment transiently reduces HIV viral loads in humans. HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned 1 , 2 , 3 . However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4 , 5 ). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated 6 , 7 , 8 , 9 , 10 . Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody 11 , in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg −1 infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8–2.5 log 10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy. By examining viral sequences in lymphoid tissue from three HIV-1-infected individuals receiving drug therapy, the authors find phylogenetic evidence for ongoing virus replication, suggesting that the antiretroviral drug concentration in the lymphoid tissue is insufficient to fully suppress the virus; using a mathematical model, they further explain why drug resistance does not necessarily arise as a result. HIV-1 persistence during drug therapy Combinations of antiretroviral drugs can reduce viral replication and reduce viral RNA to undetectable levels in blood in HIV-1 infection, but it is not clear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Steven Wolinsky and colleagues examined viral sequences in lymphoid tissue from three HIV-1 infected individuals receiving drug therapy. They find phylogenetic evidence for ongoing virus replication, suggesting that the antiretroviral drug concentration in the lymphoid tissue is insufficient to fully suppress the virus. They explain using a mathematical model why drug resistance does not necessarily arise under conditions where drug concentrations are insufficient to fully block virus replication.

Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in \"real-life\" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.