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Post-treatment control in an adult with perinatally acquired HIV following cessation of antiretroviral therapy

McMahon, James H.a,b,c; Chang, Judyd; Tennakoon, Surekhad; Dantanarayana, Ashantid; Solomon, Ajanthad; Cherry, Catherinea,b,c; Doherty, Richarde,f; Cameron, Paula,d; Lewin, Sharon R.a,d

doi: 10.1097/QAD.0000000000001472

aDepartment of Infectious Diseases, Alfred Health Hospital

bMonash University

cCentre for Population Health, Burnet Institute

dPeter Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, The University of Melbourne

eDepartment of Paediatrics, Monash University, Melbourne

fDepartment of Infectious Diseases, Monash Children's Hospital, Clayton, Victoria, Australia.

Correspondence to James H. McMahon, Department of Infectious Diseases, Alfred Health Hospital, Commercial Rd, Melbourne, VIC, 3004, Australia. Tel: +61 3 9076 6908; fax: +61 3 9076 2431; e-mail:

Received 1 March, 2017

Accepted 2 March, 2017

A 25-year-old woman who was diagnosed at 2.2 years of age with perinatally acquired HIV infection [1] and with no history of opportunistic infection commenced antiretrovirals at 3.5 years of age when her CD4+ cell count (%) was 716 cells/μl (11%; Fig. 1). Consistent with practise at that time, she initially received zidovudine, then zidovudine with lamivudine prior to starting three-drug combination antiretroviral therapy (ART) at age 4.9 years. HIV genotype performed retrospectively on a sample taken at 4.8 years of age revealed high-level resistance to thymidine analogues and lamivudine (reverse transcriptase mutations: M41LM, M184V, L210LW, T215NSTY). She achieved virological suppression on ART from 7.5 to 23 years of age with 26 of 33 plasma samples having an HIV RNA below the limit of assay quantification (range 20–400 copies/ml) with HIV RNA being 37–309 copies/ml when detected. The patient elected to stop ART in April 2015 and over the following 2 years without ART was asymptomatic, had four viral loads ranging from less than 20 to 104 copies/l with no significant changes in CD4+ T-cell counts (704–869 cells/μl) and percentage (47–51%).

Fig. 1

Fig. 1

She was infected with a subtype B virus. She was homozygous for wild-type CCR5 and 4-digit HLA typing was performed (summarised in Fig. 1). Cell-associated unspliced (CA-US) HIV RNA and DNA on sorted CD4+ T cells from peripheral blood mononuclear cells collected 16 months after cessation of ART was assessed as previously described [2]. CA-US HIV RNA was 2.4 log10 copies/million copies 18S and HIV DNA was 0.9 log10/million cell equivalents. CA-US HIV RNA and DNA was also assessed in CD4+ T-cell subpopulations sorted based on the expression of CD45RA, CCR7, and CD27 into naïve (0.8%), central (0.6%), transitional (23.1%), effector memory (0.7%), and terminally differentiated (71.9%), populations. All cells were infected, with highest to lowest levels of CA-US HIV RNA in the order: central memory, naïve, transitional memory, effector memory and then terminally differentiated. Levels of HIV DNA were highest to lowest in the order: central memory, effector memory, naïve, transitional memory and than terminally differentiated. RNA/DNA ratios were higher for central (29.3) and naïve (15.1) compared with transitional (8.8.), effector memory (2.7), and terminally differentiated (0).

Long-term virological control of HIV RNA below detectable limits of commercial assays has been well described in less than 1% of people with HIV naïve to ART and is associated with a specific HLA profile (elite controllers) [3,4]. More recently, long-term virological control has been reported after ART cessation in adults and one perinatally infected child who were treated very early after infection and subsequently stopped therapy [post-treatment control (PTC)]. In these individuals similar HLA profiles to elite controllers were not identified and most had weak HIV-specific CD8+ T-cell responses in blood [5,6].

PTC after starting ART in established chronic infection is far rarer but has also been described. Of four adult PTCs, two individuals infected with subtype B virus had transient rebound in HIV RNA before achieving undetectable levels and then had immunological decline and/or infectious complications requiring ART reinitiation. The other two individuals had no viral rebound following ART cessation and maintained immunological control with viral blips up to 1000 copies/ml. Notably these four individuals had no favourable HLA B alleles and for the three who had samples available, there were low to undetectable levels of HIV DNA, unspliced, and multiple spliced HIV RNA [7–9].

The individual in this report is unique in the literature as she demonstrates PTC in perinatally acquired HIV, following established chronic infection and a prolonged period of effective ART. Cell-associated HIV RNA and DNA were easily detectable unlike previous individuals [7,8] and were detected in all T-cell subsets including naïve T cells, in contrast to 9 of 11 adult PTCs treated in early infection who did not have detectable HIV DNA in naïve T cells [6]. This individual does not exhibit the ‘classic’ HLA B alleles seen in elite controllers [5–8] but does have HLA-B14 : 02/C08 : 02, more recently associated with elite controller [10]. Notably, patterns of HLA-C allele expression were not described in other adult PTCs reported. Interestingly, in another recently described perinatally infected PTC A23 : 01 (homozygous) and C08 : 02 alleles were present as seen in our case, but limited conclusions can be drawn based on these two reports.

In conclusion, the unique combination of perinatal acquisition, established viremia before prolonged ART and a favourable HLA allele may have led to enhanced HIV-specific immune responses that in later life allowed for control without ART, even when there was evidence of HIV persistence in all T-cell subsets, including naïve T cells. PTC can occur following initiation of ART in chronic perinatally acquired HIV infection. Establishing a large international cohort of similar individuals will be needed to define the predictors of PTC.

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J.H.M. is an NHMRC early career fellow and S.R.L. is an NHMRC practitioner fellow. J.H.M. and C.C. acknowledge the Victorian Operational Infrastructure Support Program (Department of Health, Victoria, Australia) to the Burnet Institute.

J.H.M.'s institution has received grant funding from Merck, Viiv, Bristol Myers Squibb, Pfizer and Gilead and funding for attendance at advisory boards for Gilead and Viiv.

S.R.L. is supported by NIH (U19 AI096109, UM1 AI126611), American Foundation for AIDS Research (amfAR), Wellcome Trust and has investigator initiated clinical trials funded by Viiv, Gilead, and Merck.

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Conflicts of interest

There are no conflicts of interest.

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