HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4(+) T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial.

BACKGROUND: Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. METHODS: The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 µg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4(+) T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4(+) T-cell counts and therapy compliance. RESULTS: Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4(+) T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4(+) T-cell numbers over study entry levels as compared to placebo. CONCLUSIONS: The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012.

Cervical cancer screening in a population of black South African women with high HIV prevalence: A cross-sectional study.

Cervical cancer is largely preventable through early detection, but screening uptake remains low among black women in South Africa. The purpose of this study was to determine the prevalence and factors associated with cervical cancer screening in the past 10 years among black African women in primary health care (PHC) clinics, in Gauteng Province, South Africa. This was a cross-sectional study involving 672 consecutively recruited black women at cervical cancer screening programs in PHC clinics between 2017 and 2020. An interviewer-administered questionnaire covered socio-demographics, HIV status, sexual history, cervical cancer risk factors knowledge, and screening behaviours in the past 10 years. The mean age of participants was 38 years. More than half (63%) were aged 30-49 years. Most completed high school education (75%), were unemployed (61%), single (60%), and HIV positive (48%). Only 285 (42.4%) of participants reported screening for cervical cancer in the past 10 years. Of participants that reported receiving information on screening, 27.6% (n = 176) and 13.97% (n = 89) did so from healthcare facilities and community platforms respectively. Participants aged 30 years or more were more likely to report for cervical cancer screening as compared to other categories in the past 10 years. The study found low cervical cancer screening prevalence. This calls for health education campaigns and prevention strategies that would target individual patients' contexts and stages of behavioral change. Such strategies must also consider socio-demographic and clinical correlates of cervical cancer screening and promote better integration into PHC services in South Africa.