on behalf of the CAPRISA 004 Trial Group ‡ The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18-to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use. W omen are disproportionately affected by the Acquired Immunodeficiency Syndrome (AIDS) epidemic in Africa, the region that accounts for 70% of global burden of Human Immunodeficiency Virus (HIV) infection (1). Current HIV prevention behavioral messages on abstinence, faithfulness, and condom promotion have had limited impact on HIV incidence rates in women, especially in sub-Saharan Africa, where young women bear the greatest HIV burden (2). The search for new technologies to prevent sexually transmitted HIV infection over the past three decades has had limited success. Only five of 37 randomized controlled trials, which tested 39 HIV prevention strategies, have demonstrated protection against sexual transmission of HIV infection (3). The successful trials tested medical male circumcision in South Africa (4), Kenya (5), and Uganda (6) (combined effectiveness in reducing HIV acquisition was 57%), sexually transmitted infection (STI) treatment in Tanzania (effectiveness in reducing HIV acquisition was 42%) (7), and a HIV vaccine combination in Thailand (effectiveness in reducing HIV acquisition was 31%) (8). Hence, HIV prevention technologies that women can use and control remain a pressing priority (9).Microbicides are products that can be applied to the vagina or rectum with the intention of reducing the acquisition of STIs, including HIV. An effective microbicide has the potential to alter the trajectory of the global HIV pandemic (10). Over the ...

On Nov 25, 2021, about 23 months since the first reported case of COVID-19 and after a global estimated 260 million cases and 5•2 million deaths, 1 a new SARS-CoV-2 variant of concern (VoC), omicron, 2 was reported. Omicron emerged in a COVID-19-weary world in which anger and frustration with the pandemic are rife amid widespread negative impacts on social, mental, and economic wellbeing. Although previous VoCs emerged in a world in which natural immunity from COVID-19 infections was common, this fifth VoC has emerged at a time when vaccine immunity is increasing in the world.The emergence of the alpha, beta, and delta SARS-CoV-2 VoCs were associated with new waves of infections, sometimes across the entire world. 3 For example, the increased transmissibility of the delta VoC was associated with, among others, a higher viral load, 4 longer duration of infectiousness, 5 and high rates of reinfection, because of its ability to escape from natural immunity, 6 which resulted in the delta VoC rapidly becoming the globally dominant variant. The delta VoC continues to drive new waves of infection and remains the dominant VoC during the fourth wave in many countries. Concerns about lower vaccine efficacy because of new variants have changed our understanding of the COVID-19 endgame, disabusing the world of the notion that global vaccination is by itself adequate for controlling SARS-CoV-2 infection. Indeed, VoCs have highlighted the importance of vaccination in combination with existing public health prevention measures, such as masks, as a pathway to viral endemicity. 7

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