Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy

Abstract

Background: Posttreatment control of HIV infection is a rare phenomenon primarily described among those initiating treatment with antiretroviral therapy (ART) during early/acute HIV infection. Methods: We examined a large, well-characterized cohort of HIV-infected Department of Defense beneficiaries for the presence of posttreatment controllers (PTCs) whom we defined as individuals with sustained viral suppression for ≥6 months after discontinuation of ART. We defined those who became viremic within 6 months of discontinuing ART as rapid viremics (RVs) and compared demographic and clinical characteristics, CD4 counts, and viral loads prior, during, and after ART discontinuation between the 2 groups. Results: From a cohort of 6070 patients, we identified 95 who had been treated with ART for 2 years or more who subsequently discontinued ART and had viral load assessments available after discontinuation. Four (4.2%) of these 95 met our definition of PTC. The duration of viral suppression off of ART ranged from 267 to 1058 days with 1 of the 4 restarting ART without having redeveloped a significant viremia. All 4 patients initiated ART during chronic HIV infection. Demographic and clinical characteristics of PTCs were similar to RVs. Conclusions: While posttreatment control has predominantly been described among individuals who initiated ART in early/acute HIV infection, we identified 4 PTCs who started ART during chronic infection suggesting that posttreatment control also occurs among such patients. The rarity of PTCs identified in our cohort is consistent with reports from previous studies.

Learning From the Exceptions: HIV Remission in Post-treatment Controllers

“…Furthermore, the loss of viral control was also defined differently between previous studies. Some considered 2 consecutive viral loads above 50 HIV-1 RNA copies/ml to indicate the loss of post-treatment control (8–10), while others considered 1–4 consecutive viral loads higher than 400 HIV-1 RNA copies/ml as the definition for viral rebound post-treatment interruption (7, 12, 16–18). Of note, the largest PTC study to date has been the Control of HIV after Antiretroviral Medication Pause (CHAMP) study, which identified 67 PTCs through the pooled analysis of 14 clinical studies from the AIDS Clinical Trials Group (ACTG) and other North American cohorts (6, 14, 20–32).…”

“…The median age of PTCs in these studies ranged from 27 to 46 years old. The majority of PTCs identified were male, likely reflecting the sex distribution of the clinical trial participants (6, 7, 9, 11, 12, 15–18). Intriguingly, there have been reports that female gender may be associated with a higher chance of post-treatment HIV control (10) and spontaneous control (33, 34), highlighting the need for studies focusing on female participants of treatment interruption trials.…”

“…Intriguingly, there have been reports that female gender may be associated with a higher chance of post-treatment HIV control (10) and spontaneous control (33, 34), highlighting the need for studies focusing on female participants of treatment interruption trials. In addition, the majority of PTCs have been reported by studies from North America and Europe (6, 7, 9–12, 15–18) and little is known about PTCs from outside of those regions. In an analysis of SPARTAC trial participants who initiated ART during early HIV infection, individuals with delayed viral rebound could be identified from participants enrolled in South Africa and Uganda (35).…”

“…There have been a number of subsequent studies of PTCs with a wide range of reported frequency amongst those who discontinue ART (6, 7, 9–19). This variation in reported frequency of PTCs may be attributed to different baseline characteristics of the populations in which these studies were done, as well as the heterogeneous definitions applied for defining this rare group of HIV patients (18). In this review, we will summarize the most recent findings on the clinical and immunological characteristics of PTCs, differentiate them from HIV spontaneous controllers (SCs), and discuss the role of PTCs in the search for strategies toward HIV remission and cure.…”

CRISPR/Cas9 Genome Editing to Disable the Latent HIV-1 Provirus

“…Post-treatment control has been defined as an HIV-1 viral load of <400 copies/ml for at least 24 weeks following ART interruption (ATI) (Sharaf et al, 2018). PTCs are rare, but have been identified in several patient groups as well as among patients who began ART in either acute or chronic phase of infection (Perkins et al, 2017). A recent study comparing the proviral sequences of PTCs and non-controllers (NCs) found that total number of proviruses is lower in PTCs prior to ATI (Sharaf et al, 2018).…”