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Controlled human infection models have been proposed as a strategy for accelerating SARS-CoV-2 vaccine development. But scientific and technical factors make CHIMs unlikely to accelerate the establishment of vaccine efficacy.

Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and—if successful—to galvanise treatment as prevention.

Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VE DIS ). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility ( VE SUSC ) or development of symptoms after infection (VE SYMP ). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VE SYMP and VE SUSC ) satisfying licensure criteria. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VE SUSC and VE SYMP resulting in up to 100% VE DIS . We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VE DIS are projected to prevent 23–46% of infections and 31–46% of deaths over 1 year. In comparison, vaccines with 90% VE DIS are projected to prevent 37–64% of infections and 46–64% of deaths over 1 year. In both cases, there is a greater reduction if VE DIS is mediated mostly by VE SUSC . The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VE DIS to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

Antiretroviral therapy (ART) has the potential to prevent human immunodeficiency virus (HIV) transmission by reducing the concentration of HIV in blood and genital secretions. Indeed, mathematical models with favorable assumptions suggest the potential of ART to stop the spread of HIV infection. Empirical results from ecological and population-based studies and from several short-term observational studies involving HIV status-discordant heterosexual couples suggest that ART reduces the rate of HIV transmission. A multinational, randomized, controlled trial (National Institutes of Health HPTN052) examining the reliability and durability of ART as prevention of transmission in HIV status-discordant couples is under way. The latter and other studies also consider sexual risk-taking behavior and transmission of HIV-resistant variants when ART is used as prevention. Early HIV detection and treatment (ie, test and treat) are being considered as an important prevention strategy. In this article, we review the data supporting the use of ART to prevent HIV transmission and critically examine the public health implications of this strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has generated a worldwide pandemic. The interruption of its spread depends on a combination of pharmacologic and nonpharmacologic interventions. Initial SARS-CoV-2 prevention includes social distancing, the use of face masks, environmental hygiene, and hand washing. 1 Although the most important pharmacologic interventions to prevent SARS-CoV-2 infection are likely to be vaccines, the repurposing of established drugs for short-term prophylaxis is another, more immediate option. Some researchers have promoted chloroquine and hydroxychloroquine for the treatment and prevention of illness from a variety of microorganisms, including SARS-CoV. 2 Hydroxychloroquine . . .

Acute human immunodeficiency virus (HIV) infection (AHI) can be defined as the time from HIV acquisition until seroconversion. Incident HIV infection is less well defined but comprises the time from the acquisition of HIV (acute infection) through seroconversion (early or primary HIV infection) and the following months until infection has been well established, as characterized by a stable HIV viral load (viral load set point) and evolution of antibodies with increased concentration and affinity for HIV antigens. During AHI, a viral latent pool reservoir develops, the immune system suffers irreparable damage, and the infected (often unsuspecting) host may be most contagious. It has proved very difficult to find individuals with AHI either in longitudinal cohorts of subjects at high risk for acquiring the virus or through cross-sectional screening, and the opportunity for diagnosis is generally missed during this phase. We review the technical strategies for identifying individuals with acute or incident HIV infection. We conclude that further technical advances are essential to allow more widespread detection of patients with AHI and to affect HIV treatment outcomes and transmission prevention.

Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still urgently needed. Several antiviral drugs have shown to be effective in reducing progression of COVID-19 disease. In the present work, we use an agent-based mathematical model to assess the potential population impact of the use of antiviral treatments in four countries with different demographic structure and current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium. We analyzed antiviral effects on reducing hospitalization and death, and potential antiviral effects on reducing transmission. For each country, we varied daily treatment initiation rate (DTIR) and antiviral effect in reducing transmission (AVT). Irrespective of location and AVT, widespread antiviral treatment of symptomatic adult infections (20% DTIR) prevented the majority of COVID-19 deaths, and recruiting 6% of all adult symptomatic infections daily reduced mortality by over 20% in all countries. Furthermore, our model projected that targeting antiviral treatment to the oldest age group (65 years old and older, DTIR of 20%) can prevent over 30% of deaths. Our results suggest that early antiviral treatment (as soon as possible after inception of infection) is needed to mitigate transmission, preventing 50% more infections compared to late treatment (started 3 to 5 days after symptoms onset). Our results highlight the synergistic effect of vaccination and antiviral treatment: as the vaccination rate increases, antivirals have a larger relative impact on population transmission. Finally, our model projects that even in highly vaccinated populations, adding antiviral treatment can be extremely helpful to mitigate COVID-19 deaths. These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly reduce COVID-19 hospitalizations and deaths and can help control SARS-CoV-2 transmission.

By the end of 2020, more than 19 million Americans had received the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 1 Although a substantial proportion of these infections remained asymptomatic, complications of coronavirus disease 2019 (Covid-19) had led to more than 330,000 deaths in the United States. 1 During the past year, a remarkable effort has been devoted to the development of vaccines to prevent Covid-19 and to reduce morbidity and mortality among those who are infected. Equally important is the development of treatments that can prevent the progression of Covid-19 from the inception of infection. In this issue . . .

Key Points Sexual transmission is the main route for the spread of HIV. HIV transmission can be divided into two aspects, infectiousness and susceptibility. Sexually transmitted diseases (STDs) are one of the most important ways that the efficiency of HIV transmission is increased. Factors that increase transmission HIV infectiousness can be affected by levels of HIV in the bloodstream, the levels of HIV in the genital fluids, the stage of disease, the presence of STDs, the infectiousness of the viral variant and other factors. Factors that increase susceptibility HIV susceptibility can be affected by mucosal integrity, HLA types, co-receptor variations, hormones, the presence of STDs and other factors. STDs and HIV transmission STDs increase both the likelihood of transmission and the susceptibility to HIV. STDs increase infectiousness through effects on HIV shedding, HIV replication, increases in viral diversity and through co-transmission of HIV with STDs. STDs increase susceptibility by mucosal disruption, immune changes in the genital tract and effects on the genital tract microenvironment. STDs and community-based studies Some trials have documented that the most important difference between areas of high HIV prevalence and low prevalence is not sexual behaviour but the differences in rates of certain STDs. Large intervention trials have shown mixed results in reducing HIV incidence by reducing STDs; explanations for this include the age of the HIV epidemic and the role of herpes infection More than 42 million people worldwide are now infected with HIV, in spite of sustained prevention activities. Although the spread of HIV has been primarily sexual, epidemiological studies have indicated that the efficiency of the spread of HIV is poor, perhaps as infrequently as 1 in every 1,000 episodes of sexual intercourse. However, sexually transmitted diseases (STDs) that cause ulcers or inflammation greatly increase the efficiency of HIV transmission — by increasing both the infectiousness of, and the susceptibility to HIV infection. STDs might be particularly important in the early stages of a localized HIV epidemic, when people with risky sexual behaviour are most likely to become infected. In China, eastern Europe and Russia, there has been a remarkable increase in the incidence of STDs in recent years, and this is reflected in the rapid increase in the spread of HIV in these areas. Targeted STD detection and treatment should have a central role in HIV prevention in these emerging epidemics.

Sexual and reproductive health and rights are fundamental to both human and societal wellbeing and sustainable development, and encompass a broad array of sociocultural and clinical issues that affect all people across the life course. In 2018, the Guttmacher–Lancet Commission described sexual and reproductive health as a state of physical, emotional, mental, and social wellbeing in relation to all aspects of sexuality and reproduction, not merely the absence of disease, dysfunction, or infirmity. The Commission advocated for a positive approach to sexuality and reproduction that recognises the role of pleasurable sexual relationships, trust, and communication in promoting self-esteem and overall wellbeing. The Commission also stipulated that people have a right to make decisions governing their bodies and to access services that support that right. In light of recent sociocultural changes, biomedical advances that have impacted sexual and reproductive health and rights, and the key findings of the Guttmacher–Lancet Commission, we bring together themes from this Lancet Series to discuss the new scientific developments and sociopolitical changes that affect the programmatic integration of sexual and reproductive health services. As people who present for one sexual and reproductive health service frequently have other unmet sexual and reproductive health-related needs, there are often benefits to interventions and services that address multiple connected sexual and reproductive health issues during one clinical encounter (eg, family planning visits, including testing for HIV and other sexually transmitted infections), which supports the rationale for an integrated approach. Historically, key components of sexual and reproductive health have been managed separately, partly because of siloed and inadequate funding streams and structural limitations (eg, separate location of service delivery or insufficient staff cross-training). Vertical methods have also evolved from the need for different approaches to reach key populations, who might be reluctant to seek care from primary health care clinics. We build on the findings of the papers in this Series to discuss the rationale for sexual and reproductive health programmatic integration, which has the potential to better engage patients in care by meeting their preferences, simplify the user experience, and save resources when implemented in a thoughtful, culturally tailored manner. However, wide-scale sexual and reproductive health programmatic integration faces multiple challenges, requiring broadly trained health-care providers, a range of clinical and outreach channels, and well-resourced health systems. Programmatic integration might be further constrained by societal norms and regulations (eg, punitive laws, institutional homophobia, legal restrictions on access to safe abortion, and opposition to sexual and reproductive rights). Notably, the Trump Administration's withdrawal of support from various sexual and reproductive health programmes in January, 2025, is a major threat to continued progress. This Series paper provides a call to action based on the key findings from this Series that delineates the steps needed to better integrate programmes to optimise sexual and reproductive health outcomes.