Clinical Outcome of HIV-Infected Antiretroviral-Naive Patients With Discordant Immunologic and Virologic Responses to Highly Active Antiretroviral Therapy

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 05/2008; 47(5):553-8. DOI: 10.1097/QAI.0b013e31816856c5
Source: PubMed


The prognostic significance of a response to highly active antiretroviral therapy (HAART) that is immunologically and virologically discordant is not well understood.
Four hundred four antiretroviral-naive patients initiating HAART at an urban HIV outpatient clinic in 1995 to 2004 were analyzed. The association of treatment responses at 3 to 9 months after HAART initiation with time to development of an opportunistic infection (OI) or death was determined using Cox proportional hazards modeling. Logistic regression modeling was used to examine the association between discordant responses and patient characteristics.
Of 404 patients, 70.5% experienced favorable concordant responses (CD4 cell count [CD4]+/viral load [VL]+: increase in CD4 count of >or=50 cells/microL and achievement of undetectable plasma HIV RNA level), 15.8% an immunologic response only (CD4+/VL(-)), 8.7% a virologic response only (CD4(-)/VL+), and 5.0% a concordant unfavorable response (CD4(-)/VL(-)). Both types of discordant responses (CD4+/VL(-) and CD4(-)/VL+), nonresponse (CD4(-)/VL(-)), and baseline CD4 cell count were significantly associated with earlier development of an OI or death (relative hazard [RH] = 2.81, 95% confidence interval [CI]: 1.31 to 3.97; RH = 4.83, 95% CI: 2.10 to 11.12; and RH = 0.93, 95% CI: 0.88 to 0.99, respectively). CD4+/VL(-) and CD4(-)/VL(-) were associated with nonwhite race in multivariate logistic regression models (adjusted OR = 2.83, 95% CI: 1.46 to 5.47 and adjusted OR = 6.50, 95% CI: 1.65 to 25.69, respectively).
Discordant immunologic and virologic responses at 3 to 9 months after HAART initiation play important roles in predicting long-term clinical outcomes in treatment-naive patients.

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    • "Despite the great progress in treating HIV-1 infection, in some patients starting their first treatment the effectiveness of highly active antiretroviral therapy (HAART) is still not sufficient, with consequent virological failures [1]–[4]. Furthermore, although antiretroviral therapy improves immune response, some patients infected with human immunodeficiency virus type 1 (HIV-1) present unsatisfactory CD4 T cell recovery despite achieving viral suppression, resulting in increased morbidity and mortality [4]–[10]. In this regard, an increase in CD4 cell count in the range of 50 to 150 cells/mm3 per year (generally with an accelerated response in the first 3 months of treatment) is considered an adequate CD4 response for most patients starting their first-line regimen [11]–[12]. "
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    ABSTRACT: Background We previously found that a very low geno2pheno false positive rate (FPR ≤2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. Methods The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Results Overall, at therapy start, 27% of patients had FPR ≤10 (6%, FPR ≤2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p = 0.003) and to achieve virological success (0.50 [0.26–0.94], p = 0.031) than those with pre-HAART FPR >60%. Conclusions Beyond the genotypically-inferred tropism determination, FPR ≤2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.
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    • "Some observational studies demonstrated that at least 76% of patients initiating HAART achieved an undetectable viral load within 6 months [1], but a percentage of 9%-45% did not obtain an appropriate recovery of CD4+ T cells [2,3]. This situation, commonly referred to as immuno-virological discordance, mainly associated with a low CD4+ nadir, may lead to an increased risk of progression to AIDS defining illness and death [4-8]. "
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    Full-text · Article · Nov 2013 · PLoS ONE
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    • "How such dysregulation is initiated and perpetuated has been a subject of study for the past two decades and continues to be a subject of intense interest. One of the renewed reasons for such interest lies in the finding that in spite of highly effective anti-retroviral therapy (ART) that reduces viral loads to almost undetectable levels for long periods of time still fails to promote the return of immune responses and function to “healthy” levels highlighted by the perpetuation of chronic immune activation and continued increased susceptibilities to infectious agents, accelerated incidence of end organ diseases and neoplasms [1]–[7]. Thus, it seems reasonable to define how such immune responses become abnormal and what strategies can be successfully utilized to reduce and perhaps reverse such events. "
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