Natural history of HIV-control since seroconversion

Madec, Yoann; Boufassa, Faroudy; Porter, Kholoud; Prins, Maria; Sabin, Caroline; Monforte, Antonella d’Arminio; Amornkul, Pauli N.; Bartmeyer, Barbara; Sannes, Mette; Venet, Alain; Lambotte, Olivier; Meyer, Laurence

doi:10.1097/01.aids.0000431945.72365.01

Cited by 42 publications

(51 citation statements)

References 24 publications

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“…Interestingly, CD4 counts also decreased in those who maintained virological control at the end of follow-up, around 9 cells/year, albeit at a slower pace than during natural history [32]. The association between CD4 decline and occurrence of blips during HIV control has been previously described [9,10,12], but here, and for the first time to our knowledge, we were able to model lymphocyte count dynamics before and after viral rebounds. We showed that CD4 counts and CD4/CD8 ratio declined several years before the first viral rebound was clinically observed.…”

Section: Discussionmentioning

confidence: 67%

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

et al. 2017

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ObjectiveHIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control.MethodsHICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models.ResultsWe identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds.DiscussionExpansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs.

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Section: Discussionmentioning

confidence: 67%

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

et al. 2017

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“…There are many reasons pre-ART individuals may present as aviraemic. A detailed discussion of this phenomenon is beyond the scope of this article, but undisclosed ART use dispensed from a different facility and transient virological control are just two common causes that may confound the use of VL as a confirmatory tool [19–20]. In these aviraemic individuals, further serological testing is required, but our calculation suggests that this tandem VL-ELISA approach is 10 times more costly than simply confirming every positive RDT with ELISA alone.…”

Section: Resultsmentioning

confidence: 99%

Misdiagnosed HIV infection in pregnant women initiating universal ART in South Africa

Hsiao

Zerbe

Phillips

et al. 2017

Journal of the International AIDS Society

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Introduction: Rapid diagnostic tests (RDTs) are the primary diagnostic tools for HIV used in resource-constrained settings. Without a proper confirmation algorithm, there is concern that false-positive (FP) RDTs could result in misdiagnosis of HIV infection and inappropriate antiretroviral treatment (ART) initiation, but programmatic data on FP are few. Methods: We examined the accuracy of RDT diagnosis among HIV-infected pregnant women attending public sector antenatal services in Cape Town, South Africa. We describe the proportion of women found to have started on ART erroneously due to FP RDT results based on pre-ART viral load (VL) testing and enzyme-linked immunosorbent assay (ELISA). Results: We analysed 952 consecutively enrolled pregnant women diagnosed as HIV infected based on two RDTs per local guideline and found 4.5% (43/952) of pre-ART VL results to be <50 copies/ml. After excluding 6 women who had detectable virus on subsequent VL measurements, ELISA was performed on the 37 remaining women. Of these, 3/952 (0.3%) HIV RDT diagnoses were found to be FP. We estimate that using ELISA to confirm all positive RDTs would cost $1110 (uncertainty interval $381–$5382) to identify one patient erroneously initiated on ART, while it costs $3912 for a lifetime of antiretrovirals with VL monitoring for one person. Conclusions: Compared to the cost of confirming the RDT-based diagnoses, the cost of HIV misdiagnosis is high. While testing programmes based on RDT should strive for constant quality improvement, where resources permit, laboratory confirmation algorithms can play an important role in strengthening the quality of HIV diagnosis in the era of universal ART.

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“…Recent studies of viral load dynamics early in infection have focused on small numbers of well-characterized elite or viremic HIV controllers, 3-6,16 and most reports from longitudinal cohort studies do not provide detailed information about viremia early in infection. Some studies have suggested that certain HLA alleles (e.g., HLA-B57) have a protective effect that may contribute to lower viral load set points in HIV controllers.…”

Section: Discussionmentioning

confidence: 99%

“…2-4 Other studies have shown that virologic suppression among HIV controllers is usually established within the first year of HIV infection. 3,5,6 In a recent study, over half of the individuals identified as HIV controllers had undetectable viral loads at seroconversion, and 25% achieved viremic control within six months. 6 …”

Section: Introductionmentioning

confidence: 99%

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Low-Level Viremia Early in HIV Infection

Chen

Cummings

Fogel³

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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HIV RNA levels are usually high early in HIV infection. In the HPTN 061 study, men were tested for HIV infection every six months; six (21.4%) of 28 men who acquired HIV infection during the study had low or undetectable HIV RNA at the time of HIV diagnosis. Antiretroviral drugs were not detected at the time of HIV diagnosis. False-negative HIV test results were obtained for two men using multiple assays. Antiretroviral drug resistance mutations were detected in HIV from one man. Additional studies are needed to identify factors associated with low HIV RNA levels during early HIV infection.

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Natural history of HIV-control since seroconversion

Cited by 42 publications

References 24 publications

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Misdiagnosed HIV infection in pregnant women initiating universal ART in South Africa

Low-Level Viremia Early in HIV Infection

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