Bayesian estimation of HIV acquisition dates for prevention trials.

Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data.

HIV cure research contributions from Africa in the last three decades.

Introduction: The HIV epidemic in Africa is characterized by extensive viral subtype diversity and human genetic heterogeneity which influence disease outcomes; amidst the co-morbidities that modulate HIV reservoirs and immune responses. This paper provides an overview of the quantity and spectrum of HIV cure research in context of the contributions made by African scientists toward HIV cure related research in Africa.

Methods: Using a hybrid environmental scan, we searched the Treatment Action Group website to identify registered HIV cure-related observational and interventional studies between 1995-2024.

Achieving the global agenda toward HIV cure calls for establishing a research-for-cure academy in West and Central Africa.

Despite global efforts to eliminate HIV as a public health threat, sub-Saharan Africa (SSA) still harbours about the highest burden of the pandemic, home to around 70 % of people living with HIV with limited contribution in the field of HIV cure research, especially in West and Central Africa (WCA). This gap is mainly due to challenges that researchers of this region are facing in initiating and advancing HIV cure research locally, with lesser commitment from the French-speaking countries. Furthermore, capacity-building of early career scientists on HIV cure research remains constrained due to limited awareness and language barriers to existing opportunities.

The Confluence of HIV-1 and HIV-2: Implications for Disease Progression and Insights for Therapy.

Two distinct types of human immunodeficiency virus (HIV), namely, HIV-1 and HIV-2 exist. HIV-1 is responsible for the global pandemic and has an aggressive pathogenesis. On the contrary, HIV-2 is not only less aggressive but also confined to West and Central African regions.

The impact of the PEPFAR funding freeze on HIV deaths and infections: a mathematical modelling study of seven countries in sub-Saharan Africa.

Background: On January 24, 2025, the United States government issued an executive order to freeze all foreign aid programs, including The President's Emergency Plan for AIDS Relief (PEPFAR), for 90 days. A limited waiver option became available, but its implementation remains incomplete. We estimated the impact of these policy changes on HIV deaths and new infections in seven sub-Saharan African (SSA) countries-Ethiopia, Kenya, Malawi, South Africa, Tanzania, Zambia, and Zimbabwe -, which together account for about half of all people living with HIV in SSA.

Antiretroviral therapy initiated during acute infection in women with HIV-1 clade C reduces anti-Tat antibody production and lowers CD8+ T cell activation.

Introduction: The HIV-1 Tat protein is essential for virus replication and spread and is therefore a potential target for anti-HIV therapy. Anti-Tat antibodies have been shown to slow HIV disease progression and improve antiretroviral therapy (ART) efficacy. Long-term ART results in partial reconstitution of the immune system in people living with HIV-1 (PLWH) who start treatment in the chronic phase of infection, but the impact of ART initiation in the acute phase of infection is less studied.

Distinct neutralization sensitivity between adult and infant transmitted/founder HIV-1 subtype C viruses to broadly neutralizing monoclonal antibodies.

Broadly neutralizing antibodies (bnAbs), passively administered or elicited through vaccination, are a promising strategy for novel HIV prevention, treatment or inducing ART-free remission. However, HIV diversity and evolution are a barrier to the efficacy of bnAbs and there is therefore an urgent need for continuous virus surveillance to identify bnAbs with optimal neutralization breadth and potency against transmitted/founder (TF) viruses, especially in high-burden regions. We determined the neutralization sensitivity of TF viruses isolated within seven days after first detection of heterosexually acquired infection from young women 18-23 years old (n = 39) and within 1 month after birth from in-utero infected infants (n = 21) from FRESH and Baby Cure cohorts respectively, in KwaZulu-Natal, South Africa, where HIV-1 subtype C predominates.

Distinct region-specific neutralization profiles of contemporary HIV-1 clade C against best-in-class broadly neutralizing antibodies.

While broadly neutralizing antibodies (bnAbs) have been clinically shown to prevent HIV-1 acquisition, their relative effectiveness against regionally relevant HIV-1 forms is not clear. In the present study, we examined the extent of neutralization susceptibility of contemporary HIV-1 Indian clade C at a population level along with a head-to-head comparison with that from South Africa against a panel of clinically relevant best-in-class bnAbs. Env-pseudotyped viruses encoding HIV-1 India clade C were found to be best neutralized by the V3 glycan-directed bnAbs (10-1074 and BG18) and select CD4 binding site (CD4bs)-directed bnAbs (VRC07, N6, and 1-18); however, they demonstrated significant resistance to V1/V2 apex-directed bnAbs.

Genetic determinants of HIV-1 subtype C Nef-mediated SERINC3 down-regulation.

Background: Nef-mediated down-regulation of the host restriction factors SERINC3 and SERINC5 significantly enhances HIV-1 infectivity. Natural Nef polymorphisms that affect SERINC3 down-regulation are not as well-characterised as those that affect SERINC5 down-regulation, particularly in HIV-1 subtype C infection. We therefore aimed to identify genetic determinants of SERINC3 down-regulation by subtype C Nef.

Effect of the vaginal live biotherapeutic LACTIN-V (Lactobacillus crispatus CTV-05) on vaginal microbiota and genital tract inflammation among women at high risk of HIV acquisition in South Africa: a phase 2, randomised, placebo-controlled trial.

Background: Absence of vaginal lactobacilli and accompanying genital inflammation is associated with HIV acquisition. We aimed to assess how a vaginal live biotherapeutic containing Lactobacillus crispatus affects cervicovaginal microbiota and markers of HIV susceptibility in South African women.

Methods: This randomised, placebo-controlled, phase 2 trial evaluated LACTIN-V (L crispatus CTV-05), a vaginal live biotherapeutic, compared with placebo in cisgender women in South Africa, aged 18-23 years, recruited at a community-based research clinic.

IgG antibody response to Mycobacterium tuberculosis curli pili (MTP) in people from different geographical regions in Sub-Saharan Africa.

Previously, a slot blot or an indirect enzyme-linked immunosorbent assay (ELISA) using a synthetic or purified MTP antigen, conceptually demonstrated IgG antibody induction in pulmonary TB patients, albeit with small sample sizes and differing sensitivity. Therefore, we evaluated an IgG MTP ELISA in larger populations from The Gambia (n = 549), Uganda (n = 161), and South Africa (n = 193), comprising human immunodeficiency virus (HIV) positive and negative, with microbiologically confirmed active TB. The association between the IgG level and demographic characteristics was determined by multivariate logistic regression.

HIV-1 Gag-protease-driven replicative capacity influences T-cell metabolism, cytokine induction, and viral cell-to-cell spread.

High replicative capacity (RC) HIV-1 strains are associated with elevated viral loads and faster disease progression in the absence of antiretroviral therapy. Understanding the mechanisms by which high RC strains adversely affect the host is essential for developing novel anti-HIV interventions. This study investigates cellular metabolism, cytokine induction, and cell-to-cell spread as potential mechanisms differentiating clinical outcomes between low and high RC strains of HIV-1.

Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection.

Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are a barrier to cure efforts. Early antiretroviral therapy (ART) enables post-treatment viral control in some cases, but mechanisms remain unclear. We hypothesised that ART initiated before peak viremia impacts HIV-1 subtype C reservoirs.

'It is scary to pause treatment': perspectives on HIV cure-related research and analytical treatment interruptions from women diagnosed during acute HIV in Durban, South Africa.

Background: HIV remains a major challenge in KwaZulu-Natal, South Africa, particularly for young women who face disproportionate risks and barriers to prevention and treatment. Most HIV cure trials, however, occur in high-income countries.

Objective: To examine the perspectives of young women diagnosed with acute HIV in a longitudinal study, focusing on their perceptions on ATI-inclusive HIV cure trials and the barriers and facilitators to participation.

Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.

Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.

Target product profile for cell-based and gene-based therapies to achieve a cure for HIV.

This target product profile (TPP) highlights the minimal and optimal characteristics for ex-vivo and in-vivo cell and gene therapy-based products aimed at achieving an HIV cure (ie, durable antiretroviral-free viral control). The need for an effective, safe, scalable, affordable, accessible, and acceptable cure for HIV infection remains a major global priority. The possibilities for cell and gene therapy-based products for an HIV cure are rapidly expanding.

Service.

There are many dimensions to scientific life. We asked investigators about the impact of service to the scientific community and beyond and how service has shaped their experience, perspective, and research path.

Dynamics of the blood plasma proteome during hyperacute HIV-1 infection.

The complex dynamics of protein expression in plasma during hyperacute HIV-1 infection and its relation to acute retroviral syndrome, viral control, and disease progression are largely unknown. Here, we quantify 1293 blood plasma proteins from 157 longitudinally linked plasma samples collected before, during, and after hyperacute HIV-1 infection of 54 participants from four sub-Saharan African countries. Six distinct longitudinal expression profiles are identified, of which four demonstrate a consistent decrease in protein levels following HIV-1 infection.

Dysfunctional bronchoalveolar effector memory CD8 T cells in tuberculosis-exposed people living with antiretroviral-naïve HIV infection.

HIV causes susceptibility to respiratory pathogens, including tuberculosis (TB), but the underlying immunological mechanisms remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from TB-exposed people in the presence or absence of antiretroviral-naïve HIV co-infection. Bulk transcriptional profiling demonstrated compartment-specific enrichment of immunological processes.

Phylogenetic evidence of extensive spatial mixing of diverse HIV-1 group M lineages within Cameroon but not between its neighbours.

From the perspective of developing relevant interventions for treating HIV and controlling its spread, it is particularly important to comprehensively understand the underlying diversity of the virus, especially in countries where the virus has been present and evolving since the cross-species transmission event that triggered the global pandemic. Here, we generate and phylogenetically analyse sequences derived from the (2010 bp;  = 115), partial (345 bp;  = 36), and (719 bp;  = 321) genes of HIV-1 group M (HIV-1M) isolates sampled between 2000 and 2022 from two cosmopolitan cities and 40 remote villages of Cameroon. While 52.