Antiretroviral Therapy for the Prevention of HIV-1 Transmission

Abstract

BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1– negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

Incidence, Predictors, and Outcomes of Implantable Cardioverter‐Defibrillator Discharge Among People Living With HIV

“…Furthermore, the overall viral suppression rate in this study was 51%. This rate of viral suppression is comparable to other contemporary observational clinical cohort studies (suppression rates of 45%–62%)1, 5, 38 and studies in this region (viral suppression rate of 58%),39 but is lower than observed in more recent registries and clinical trials 40, 41, 42. It is also possible that the PHIV with an ICD were sicker for other reasons, such as concomitant infections/lower CD4 cell count, and therefore more likely to have an ICD discharge.…”

Polyvalent vaccine approaches to combat HIV‐1 diversity

“…HIV/AIDS has remained a public health threat for many decades now, and concerted global efforts have resulted in successful prevention and treatment strategies that are beginning to show success in curtailing the spread and pathogenicity of this disease. Importantly, death rates and new HIV‐1 infections have declined in many regions of the world 3. Despite these advances, HIV‐1 remains a devastating global health problem.…”

“…Over half of the people living with HIV‐1 are not receiving treatment, and many infected people are not aware of their infection. In 2015, there were an estimated 36.7 million people living with HIV‐1, and approximately 1 million of these died AIDS‐related deaths 3. Moreover, by compromising the immune system, HIV‐1 increases the morbidity and mortality of other devastating diseases, including tuberculosis4 and malaria,5 which are endemic to regions with a high HIV‐1 prevalence.…”

“…Within each of the more than 70 million people who have been infected with HIV‐1 since the beginning of the pandemic,3 an extraordinary evolutionary process has played out. High baseline rates of HIV‐1 mutation6 and replication7 lay a foundation of viral diversity, and this combined with continuous immune‐driven selection generates a complex and unique viral quasispecies in each infected person 8, 9, 10, 11, 12.…”

The importance of serostatus awareness in arresting the spread of HIV

“…Moreover, studies such as START 2 and TEMPRANO 3 have indicated that individuals benefit from initiating treatment as soon as they are diagnosed. HPTN 052 4, the PARTNERS study 5, 6 and Opposites Attract 7 have demonstrated that individuals on effective treatment do not transmit HIV to their partners. Additionally, the use of tenofovir co‐formulated with emtricitabine for pre‐exposure prophylaxis adds to the armamentarium of prevention technologies enabling individuals to avoid becoming infected.…”