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When to initiate antiretroviral therapy in patients with newly diagnosed HIV infection and TB has been debated. In this study from Cambodia, giving antiretrovirals 2 weeks after the start of TB therapy was superior to therapy begun at 8 weeks, with a decrease in mortality. Tuberculosis is a major cause of death in persons infected with the human immunodeficiency virus (HIV), especially in resource-limited settings. 1 , 2 Despite effective tuberculosis therapy, mortality is particularly high among patients with severe immunosuppression. 3 , 4 Although mortality among HIV-infected patients has been reported to be approximately 30% within the first 2 months of tuberculosis treatment if antiretroviral therapy (ART) is withheld, 5 the timing for starting ART in patients with tuberculosis has remained unclear. Arguments that support delayed initiation of ART include concern about the combined toxic effects of drugs, an increased risk of the immune reconstitution inflammatory syndrome (IRIS), and . . .

The role of Antibody-dependent cellular cytotoxicity (ADCC) responses in HIV-1 controllers is still unclear due to the heterogeneity of these patients. We analyzed 67 HIV-1 controllers and found significantly higher levels of ADCC antibodies in controllers versus viremic subjects (p = 0.017). Moreover, multivariate analysis revealed significantly higher ADCC titers in HLA B57- controllers compared to HLA-B57+ ones (p = 0.0086). These data suggest a role for ADCC in immune control of HIV, especially in HLA B57 negative controllers.

The prevalence of Ebola virus infection among people who have been in contact with patients with Ebola virus disease remains unclear, but is essential to understand the dynamics of transmission. This study aimed to identify risk factors for seropositivity and to estimate the prevalence of Ebola virus infection in unvaccinated contact persons. In this retrospective, cross-sectional observational study, we recruited individuals between May 12, 2016, and Sept 8, 2017, who had been in physical contact with a patient with Ebola virus disease, from four medical centres in Guinea (Conakry, Macenta, N'zérékoré, and Forécariah). Contact persons had to be 7 years or older and not diagnosed with Ebola virus disease. Participants were selected through the Postebogui survivors' cohort. We collected self-reported information on exposure and occurrence of symptoms after exposure using a questionnaire, and tested antibody response against glycoprotein, nucleoprotein, and 40-kDa viral protein of Zaire Ebola virus by taking a blood sample. The prevalence of Ebola virus infection was estimated with a latent class model. 1721 contact persons were interviewed and given blood tests, 331 of whom reported a history of vaccination so were excluded, resulting in a study population of 1390. Symptoms were reported by 216 (16%) contact persons. The median age of participants was 26 years (range 7–88) and 682 (49%) were male. Seropositivity was identified in 18 (8·33%, 95% CI 5·01–12·80) of 216 paucisymptomatic contact persons and 39 (3·32%, 5·01–12·80) of 1174 (2–4) asymptomatic individuals (p=0·0021). Seropositivity increased with participation in burial rituals (adjusted odds ratio [aOR] 2·30, 95% CI 1·21–4·17; p=0·0079) and exposure to blood or vomit (aOR 2·15, 1·23–3·91; p=0·0090). Frequency of Ebola virus infection varied from 3·06% (95% CI 1·84–5·05) in asymptomatic contact persons who did not participate in burial rituals to 5·98% (2·81–8·18) in those who did, and from 7·17% (3·94–9·09) in paucisymptomatic contact persons who did not participate in burial rituals to 17·16% (12·42–22·31) among those who did. This study provides a new assessment of the prevalence of Ebola virus infection among contact persons according to exposure, provides evidence for the occurrence of paucisymptomatic cases, and reinforces the importance of closely monitoring at-risk contact persons. Institut National de la Santé et de la Recherche Médicale, Reacting, the French Ebola Task Force, Institut de Recherche pour le Développement, and Montpellier University Of Excellence-University of Montpellier.

In an optimum One Health approach, because southeast Asian bat species harbour coronaviruses similar to SARS-CoV-2, coronavirus surveillance14 should have been triggered with regular biobanking from reservoirs, surveillance of transmission to potentially susceptible animals or to humans in contact with those animals, and an analysis of the environmental factors favouring transmission (ie, analysis of ecosystems and factors associated with carriage; figure). The omicron (B.1.1.529) variant is speculated to have possibly emerged after reverse zoonosis (figure).19 This understanding of potential evolutionary processes through reverse virus zoonosis and their consequences is part of the One Health strategy that needs to be addressed for each emergence (eg, monkeypox virus; appendix p 2). The panel published a new inclusive definition of One Health, encouraging intersectoral, but also interdisciplinary and multistakeholder approaches.21,22 Several One Health operationalisation plans have also been developed, such as the One Health Joint Plan of Action developed by the Quadripartite Agreement, working together for the health of humans, animals, plants and the environment,23 and the One Health operational framework proposed by The World Bank.24 However, although declarations and action plans provided by each stakeholder in their own sector are a prerequisite for any change, they are not enough. Conversely, this global understanding is more advanced in the ecology and animal health sectors, although One Health activities are poorly funded and mostly theoretical.

Hepatitis C virus (HCV) causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU) infected by human immunodeficiency virus type 1 (HIV-1) are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1) gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

In this trial of preexposure prophylaxis with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in men who have sex with men, TDF-FTC was found to be effective in preventing HIV-1 infection when it was taken before sexual activity. The prevention of infection with human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) remains a major public health challenge. 1 Owing to the lack of an effective HIV vaccine, consistent condom use remains the cornerstone of prevention, but biomedical interventions such as male circumcision and the use of antiretroviral drugs for the treatment of HIV infection represent additional prevention strategies. 2 – 5 Among the promising interventions is preexposure prophylaxis, in which antiretroviral drugs are started in HIV-negative persons before potential exposure to the virus. Daily oral preexposure prophylaxis with either tenofovir disoproxil fumarate (TDF) or the combination of TDF and . . .

Virological failure on a boosted-protease inhibitor (PI/r) first-line triple combination is usually not associated with the detection of resistance mutations in the protease gene. Thus, other resistance pathways are being investigated. First-line PI/r monotherapy is the best model to investigate in vivo if the presence of mutations in the cleavage sites (CS) of gag gene prior to any antiretroviral treatment might influence PI/r efficacy. 83 patients were assigned to initiate antiretroviral treatment with first-line lopinavir/r monotherapy in the randomised Monark trial. We compared baseline sequence of gag CS between patients harbouring B or non-B HIV-1 subtype, and between those who achieved viral suppression and those who experienced virological failure while on LPV/r monotherapy up to Week 96. Baseline sequence of gag CS was available for 82/83 isolates; 81/82 carried at least one substitution in gag CS compared to HXB2 sequence. At baseline, non-B subtype isolates were significantly more likely to harbour mutations in gag CS than B subtype isolates (p<0.0001). Twenty-three patients experienced virological failure while on lopinavir/r monotherapy. The presence of more than two substitutions in p2/NC site at baseline significantly predicted virological failure (p = 0.0479), non-B subtype isolates being more likely to harbour more than two substitutions in this specific site. In conclusion, gag cleavage site was highly polymorphic in antiretroviral-naive patients harbouring a non-B HIV-1 strain. We show that pre-therapy mutations in gag cleavage site sequence were significantly associated with the virological outcome of a first-line LPV/r single drug regimen in the Monark trial.

The isolation of HIV-1 was a fundamental step for understanding HIV and the disease it causes. Here, Françoise Barré-Sinoussi, Anna Laura Ross and Jean-François Delfraissy look back on three decades of research that have changed the lives of people infected with HIV and have inspired hope for a cure. This year marks the thirtieth anniversary of the publication of the study that first reported the isolation of HIV-1. In this Timeline article, we provide a historical perspective of some of the major milestones in HIV science, highlighting how translational research has affected treatment and prevention of HIV. Finally, we discuss some of the current research directions and the scientific challenges ahead, in particular in the search for a cure for HIV.