Viral Blips Research Articles

1168Use of First Positive Cytomegalovirus (CMV) PCR Determination to Differentiate a Viral Blip From Established CMV Infection in Transplant Recipients

1168Use of First Positive Cytomegalovirus (CMV) PCR Determination to Differentiate a Viral Blip From Established CMV Infection in Transplant Recipients

Unboosted atazanavir with lamivudine/emtricitabine for patients with long-lasting virological suppression.

IntroductionUnboosted atazanavir (ATV) including regimens have been investigated as a ritonavir-sparing simplification strategy. No data are available on removal of one NRTI in subjects effectively treated with unboosted atazanavir+2NRTIs. We present the 48-week virological efficacy and safety of unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC) (lamivudine/emtricitabine/Reyataz©, LAREY Study).Materials and MethodsSingle arm, prospective, pilot study on HIV-treated patients, HBsAg negative, with HIV-RNA<50 cps/mL since at least 2 years, who switched from ATV+2NRTIs to ATV 400 mg QD +3TC or FTC. Virological failure was defined as 2 consecutive values of HIV-RNA>50 cps/ml; viral blip was defined as a single HIV-RNA value>50 cps/ml not subsequently confirmed. Results as median (IQR). Changes between baseline (BL) and week 48 assessed by the Wilcoxon signed rank test.ResultsForty patients enrolled: 75% males, 51 (47–54) years, 14% HCV co-infected, infected with HIV since 16 (9–21) years, on antiretroviral therapy since 13 (5–16) years, with a nadir CD4+ of 254 (157–307) cells/mm3, virologically suppressed since 4.2 (2.2–5.4) years; 53 patients switched from a tenofovir (TDF)-based regimens; ATV was associated with 3TC in 83% patients. No virological failures or discontinuations were observed; three patients had a single viral blip in the range 50–250 copies/mL; CD4+ increased from 610 (518–829) cells/mm3 at BL to 697 (579–858) cells/mm3 at week 48 [48-week change: 39 (−63/+160) cells/mm3 p=0.081]. Three clinical events were observed (one herpes zoster, one pneumonia, one syphilis) in absence of renal lithiasis, AIDS-defining or drug-related events or death. Overall, significant 48-week amelioration of ALP [BL: 83 (71–107) mg/dL; 48-week change: −15 (−27/−8) mg/dL p<0.0001] and CKD-EPI [BL: 100 (86–108) ml/min/1.73 m2; 48-week change: 1.5 (−3/+8) ml/min/1.73 m2, p=0.042] were observed. Patients switching from TDF (Table 1) significantly improved CD4+, lymphocytes, hepatic profile, renal profile and ALP; these patients had also a modest but significant decrease in haemoglobin.ConclusionsSwitch from an unboosted atazanavir-based regimen to ATV+3TC or FTC regimen was effective and safe in this small sample, supporting the hypothesis of a potential two-steps de-intensification (removal of ritonavir and removal of one NRTI) in patients on long-lasting virological suppression.

The importance of viral blips and duration of therapy initiated in primary infection in maintaining viral control after stopping cART.

IntroductionAfter achieving undetectable HIV-RNA on cART, on cessation, HIV-RNA rebounds to pre-treatment values for the majority due to the presence of an inaccessible viral reservoir. There is some evidence that cART during primary HIV infection (PHI) limits the reservoir size, optimizing the chance of maintaining viral control off cART. Data are required to predict possible viral controllers for treatment interruption following cART. This analysis aims to investigate the effect of cART duration and the rate of viral blips while on cART initiated in PHI, and other factors on maintaining viral control for those stopping cART.Material and MethodsUsing CASCADE data on HIV seroconverters, we characterized virologic blip (viral suppression on cART followed by a single HIV-RNA above a blip threshold and a subsequent measure below the threshold without cART change) rates for those starting cART within six months of seroconversion (SC). Using Cox models, we examined the effect of the following factors on time to virologic rebound (HIV-RNA>1000) after cART stop: cART duration, severity/rate of blips on cART, time from SC to cART start, cART class, SC year, SC age, CD4 at cART start/stop, sex and HIV risk group.ResultsThe 660 individuals initiating cART in PHI were mostly male (91%), seroconverting between 1995 and 2012, with a median (IQR) age of 34 (29, 41) years mostly infected through sex between men (73%). Median cART duration was 14.8 (7.0, 31.7) months initiated at a median 1.9 (0.5, 3.9) months post SC. 13 (11, 16), 9 (7, 11), 6 (5, 9) and 7 (6, 10)% of individuals experienced blips >50, 100, 200 and 400 copies/mL, respectively. Of those who experienced blips, most (77–90%, depending on blip threshold) experienced just one. Among 250 individuals with undetectable HIV-RNA at cART stop, median time to rebound was 1.6 (0.30, 5.8) months. Time on cART was the only factor independently associated with control after stopping, HR for rebound=0.91 (0.86, 0.98) per extra six months spent on cART, HR for ever blipping >400 copies/mL while on cART=0.88 (0.40, 1.93).ConclusionsBlips occur in about 10% of individuals who initiate cART in PHI, most of who experience only one blip, but was not predictive of subsequent virologic rebound. Increasing time spent on cART initiated in PHI could increase time of virological suppression after cART stop.

Residual Viremia Is Preceding Viral Blips and Persistent Low-Level Viremia in Treated HIV-1 Patients

BackgroundIt has been suggested that low-level viremia or blips in HIV-infected patients on antiretroviral treatment are related to assay variation and/or increased sensitivity of new commercial assays. The 50-copy cut-off for virologic failure is, therefore, under debate.MethodsTreated patients with low-level viremia (persistent viral loads (VL) of 50–1000 copies/mL, group A, N = 16) or a blip (single detectable VL, group B, N = 77) were compared to a control group (consistently suppressed viremia since start therapy (<50 copies/mL), N = 79). Residual viremia (detectable viral RNA <50 copies/ml) in the year preceding the first VL above 50 copies/mL (T0) was determined using Roche Cobas-Amplicor v1.5 or CAP-CTM v2.0. Subsequent virologic failure (2 consecutive VLs>500 or 1 VL>1000 copies/mL that was not followed by a VL<50 copies/mL; median follow up 34 months) was assessed.ResultsSignificantly more patients in groups A and B had residual viremia in the year preceding T0 compared to controls (50% and 19% vs 3% respectively; p<0.001). Residual viremia was associated with development of low-level viremia or blips (OR 10.9 (95% CI 2.9–40.6)). Subsequent virologic failure was seen more often in group A (3/16) and B (2/77) than in the control group (0/79).ConclusionResidual viremia is associated with development of blips and low-level viremia. Virologic failure occurred more often in patients with low-level viremia. These results suggest that low-level viremia results from viral production/replication rather than only assay variation.

Stochastic population switch may explain the latent reservoir stability and intermittent viral blips in HIV patients on suppressive therapy

Highly active antiretroviral therapy can suppress plasma viral loads of HIV-1 infected individuals to below the detection limit of standard clinical assays. However, low-level viremia still persists. Many patients also have transient viral load measurements above the detection limit (the so-called “viral blips”). The latent reservoir consisting of latently infected CD4+ T cells represents a major obstacle to HIV-1 eradication. These cells can be activated to produce virions but the size of the latent reservoir is relatively stable. The mechanisms underlying low viral load persistence, emergence of intermittent viral blips and stability of the latent reservoir are not well understood. Cellular and viral transcription factors play an important role in the establishment and maintenance of HIV-1 latency. Infected cells with intermediate transcriptional activities may either revert to a latent state or become highly activated and produce virions due to intracellular perturbations. Here we develop a mathematical model that includes such stochastic population switch. We demonstrate that the model can generate a stable latent reservoir, intermittent viral blips, as well as low-level viremia persistence. Latently infected cells with intermediate transcription activities may maintain their size through a high level of homeostatic proliferation, while cells with low transcriptional activities are likely to be maintained through the reversion from cells with intermediate transcription activities. Simulations also suggest that treatment intensification or activation therapy may not help to eradicate the latent reservoir. Blocking the proliferation of latently infected cells might be a good strategy. These results provide more insights into the long-term dynamics of virus and latently infected cells in HIV patients on suppressive therapy and may help to develop novel treatment strategies.

Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV‐1‐infected individuals

Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips. HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients. Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/μL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46). The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.

CP-023 Effect of treatment complexity on medicines adherence and incidence of blips in HIV/HCV co-infected patients

BackgroundAnti-HCV treatment may add significant complexity to antiretroviral treatment (ART). The complexity of the medicines regimen could be a risk factor for non-adherence or increasing incidence of blips.PurposeTo determine if...

The Significance of HIV ‘Blips’ in Resource-Limited Settings: Is It the Same? Analysis of the Treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD)

IntroductionMagnitude and frequency of HIV viral load blips in resource-limited settings, has not previously been assessed. This study was undertaken in a cohort from a high income country (Australia) known as AHOD (Australian HIV Observational Database) and another cohort from a mixture of Asian countries of varying national income per capita, TAHOD (TREAT Asia HIV Observational Database).MethodsBlips were defined as detectable VL (≥ 50 copies/mL) preceded and followed by undetectable VL (<50 copies/mL). Virological failure (VF) was defined as two consecutive VL ≥50 copies/ml. Cox proportional hazard models of time to first VF after entry, were developed.Results5040 patients (AHOD n = 2597 and TAHOD n = 2521) were included; 910 (18%) of patients experienced blips. 744 (21%) and 166 (11%) of high- and middle/low-income participants, respectively, experienced blips ever. 711 (14%) experienced blips prior to virological failure. 559 (16%) and 152 (10%) of high- and middle/low-income participants, respectively, experienced blips prior to virological failure. VL testing occurred at a median frequency of 175 and 91 days in middle/low- and high-income sites, respectively. Longer time to VF occurred in middle/low income sites, compared with high-income sites (adjusted hazards ratio (AHR) 0.41; p<0.001), adjusted for year of first cART, Hepatitis C co-infection, cART regimen, and prior blips. Prior blips were not a significant predictor of VF in univariate analysis (AHR 0.97, p = 0.82). Differing magnitudes of blips were not significant in univariate analyses as predictors of virological failure (p = 0.360 for blip 50–≤1000, p = 0.309 for blip 50–≤400 and p = 0.300 for blip 50–≤200). 209 of 866 (24%) patients were switched to an alternate regimen in the setting of a blip.ConclusionDespite a lower proportion of blips occurring in low/middle-income settings, no significant difference was found between settings. Nonetheless, a substantial number of participants were switched to alternative regimens in the setting of blips.

Viral Blips May Not Need a Trigger: How Transient Viremia Can Arise in Deterministic In-Host Models

Recurrent infection is characterized by short episodes of high viral reproduction, separated by long periods of relative quiescence. This recurrent pattern is observed in many persistent infections, including the “viral blips” observed during chronic infection with the human immunodeficiency virus (HIV). Although in-host models which incorporate forcing functions or stochastic elements have been shown to display viral blips, simple deterministic models also exhibit this phenomenon. We describe an analytical study of a 4-dimensional HIV antioxidant-therapy model which exhibits viral blips, showing that an increasing, saturating infectivity function contributes to the recurrent behavior of the model. Using dynamical systems theory, we hypothesize four conditions for the existence of viral blips in a deterministic in-host infection model. In particular, we explain how the blips are generated, which is not due to homoclinic bifurcation since no homoclinic orbits exist. These conditions allow us to develop very simple (2- and 3-dimensional) infection models which produce viral blips, and we determine the complete parameter range for the 3-dimensional model in which blips are possible, using stability analysis. We also use these conditions to demonstrate that low-dimensional in-host models with linear or constant infectivity functions cannot generate viral blips. Finally, we demonstrate that a 5-dimensional immunological model satisfies the conditions and exhibits recurrent infection even with constant infectivity; thus, an increasing, saturating infectivity function is not necessary if the model is sufficiently complex.

SIGEST

The SIGEST paper in this issue, “Viral Blips May Not Need a Trigger: How Transient Viremia Can Arise in Deterministic In-Host Models,” by Wenjing Zhang, Lindi M. Wahl, and Pei Yu, is from the SIAM Journal on Applied Mathematics. The authors have expanded the introduction to explain the details of the problem and survey the prior work on this subject. In this paper the authors analyze dynamic models of recurrent infections in individuals (the hosts in the title). These viral infections, HIV being a well-known example, have long periods of low viral activity punctuated by episodes of high viral reproduction. Previous models of the dynamics of these viral blips used either stochastic components or forcing terms as the triggers to simulate the phenomenon. The new models in the paper require neither stochastic features nor forcing terms and generate the viral blips by dynamic bifurcations. Such models had been investigated by others who simulated the blips numerically, but, until this paper, there were no analytical studies that supported the computational observations. While the analysis is very technical, the paper also has several simple examples. Any reader will enjoy playing with those.

Ritonavir-Boosted Lopinavir as Maintenance Monotherapy in HIV-Infected Patients Who Achieved Viral Suppression during a Second-Line Protease Inhibitor–Based Regimen

Eligibility criteria were (1) having previously failed first-line nonnucleoside reverse transcriptase inhibitor–based regimens and (2) having achieved virologic suppression &gt;6 months while receiving a protease inhibitor (PI)-based regimen as second-line treatment. Eligible participants were randomized to receive either (1) ritonavir-boosted lopinavir (LPV/r) monotherapy (n = 29) or (2) LPV/r with optimized background regimens (OBRs; n = 31). Median duration of viral suppression before randomization was 45 months. At week 48, viral suppression during LPV/r monotherapy was 86.2% and did not differ from the suppression achieved with LPV/r with OBRs (87.1%, P = 1.000). However, persistent viremia during LPV/r monotherapy tended to be higher than during LPV/r with OBRs (10.3% versus 3.2%, P = .346). History of viral blip during virologic suppression with second-line PI-based regimen is a predictor of achieving viral suppression at all visits (adjusted relative risk 0.255 [95% confidence interval 0.080-0.821], P = .022). Use of LPV/r monotherapy as maintenance regimen in this study produced persistent viremia that tended to be higher than LPV/r monotherapy with OBRs.

7.0 Managing virological failure

7.0 Managing virological failure

2.0 Recommendations and auditable outcomes

2.0 Recommendations and auditable outcomes

Backward bifurcation in a mathematical model for HIV infection in vivo with anti-retroviral treatment

Anti-retroviral treatments (ART) such as HAART have been used to control the replication of HIV virus in HIV-positive patients. In this paper, we study an in-host model of HIV infection with ART and carry out mathematical analysis of the global dynamics and bifurcations of the model in different parameter regimes. Among our discoveries is a parameter region for which backward bifurcation can occur. Biologically, the catastrophic behaviors associated with backward bifurcations may explain the sudden rebound of HIV viral load when ART is stopped, and possibly provide an explanation for the viral blips during ART suppression of HIV.

Cobas Ampliprep/Cobas TaqMan HIV-1 v2.0 Assay: Consequences at the Cohort Level

BackgroundHigh-sensitive real-time PCR assays are routinely used to monitor HIV-1 infected subjects. Inter-assay discrepancies have been described at the low viral load (VL) end, where clinical decisions regarding possible virological rebound are based.MethodsA retrospective study was performed to analyze frequencies of viral blips after transition to the COBAS Ampliprep/COBAS TaqMan v2.0 HIV-1 assay (Taqman v2.0) in patients with prior undetectable VLs as measured with the Roche Cobas Ampliprep Amplicor HIV-1 Monitor Test, v1.5 (Amplicor) and was evaluated in comparison to a group of patients monitored with the Abbott Real-time HIV-1 assay (Abbott RT) during the same period of time.Results85 of 373 patients with VLs below the limit of quantification with Amplicor had VLs >50 copies/mL after transition to the TaqMan v2.0 assay. Among these 74.1% had VLs ranging from 50–499 copies/mL, 22.9% had VLs >500 copies/mL. From 22 patients with initial Taqman v2.0 based VLs exceeding 500 copies/mL, 6 patients had VLs <20 copies/mL after novel VL measurement on a next visit. In our control group with VL quantification using the Abbott RT assay, only 1 patient became detectable and showed a VL of <40 copies/mL after new measurement.ConclusionsTransition to the Taqman v2.0 assay was accompanied by an increase of quantifiable HIV-1 VLs in patients with long term viral suppression under antiretroviral therapy that might be attributed to technical shortcomings of the Taqman v2.0 assay. A high test variability at the low VL end but also beyond was observed, making meaningful clinical interpretation of viral blips derived from different assays difficult.

Stability analysis for HIV infection delay model with protease inhibitor

In this article, we considered a model of HIV-1 infection with a protease inhibitor therapy and three delays. The frequency of the bifurcating periodic solution as well as the threshold value is approximated numerically using realistic parameter. The estimated threshold value is realistic and the frequency of the oscillations is consistent with that of the observed viral blips.

Short Communication: HIV Blips While on Antiretroviral Therapy Can Indicate Consistently Detectable Viral Levels Due to Assay Underreporting

Viral blips, where HIV RNA plasma viral load (pVL) intermittently increases above the lower limit of assay detection, are a cause for concern. We investigated a number of hypotheses for their cause. We assessed HIV RNA, and total and episomal HIV DNA from 16 individuals commencing antiretroviral therapy (ART) consisting of raltegravir and tenofovir/emtricitabine for 3 years, using two assays: a single-copy assay [SCA; lower limit of quantification (LLOQ), <1 copy/ml] and the Amplicor assay (LLOQ of 50 copies/ml). Two individuals exhibited viral blips. From week 20 onward, the period where ART had achieved its final suppressive levels, pVL ranged from <1 to 330 copies/ml, except for one individual at the final time. Both assays were 98% consistent (108/110) in assessing pVL <50 copies/ml, but the Amplicor assay registered 56% of samples (19/34) as below the LLOQ that were in the 50 to 1000 copy/ml range as quantified by SCA. pVL changes between successive time points did not correlate with changes in cellular infection as measured through either total or episomal HIV DNA. Changes in pVL were correlated (negatively) with changes in total CD4(+) T cell numbers (p=0.003), naive (CD45RO(-)CD62L(+)CD4(+)), natural regulatory (CD45RO(-)CD25(+)CD127(-)CD4(+)), activated effector (CD45RO(+)CD38(++)CCR5(+)CD8(+)), but not activated (CD38(+)HLA-DR(+)) CD4(+) T cells. Patients receiving stable, seemingly suppressive ART can have pVL near the 50 copy LLOQ at multiple time points. The high Amplicor assay error rate around this level implies that viral blips underrepresent pVL being more consistently above the LLOQ. Activation of latently infected cells is less likely to contribute to this phenomenon.

Seminal Human Immunodeficiency Virus Blips and Structured Natural Conception In Serodiscordant Couples

TO THE EDITOR—As the prognosis for human immunodeficiency virus (HIV)– infected patients has improved with effective therapies, the prospect of raising children has become a realistic expectation among many serodiscordant couples. For seronegative women, structured natural conception can offer an appealing (and affordable) balance between getting pregnant and avoiding infection from their seropositive male partner. However, despite sustained long-term suppression of plasma viremia by antiretroviral therapy below the level of detection, some HIV-infected men intermittently and unpredictably have detectable free or cell-associated HIV in their semen, independent of drug regimen or seminal drug levels [1–4]. Shedding has been associated with transient increases in T-cell activation confined to the male genital tract [4–6]. The finite (albeit quite small) possibility of infecting a seronegative partner during intercourse even when the seropositive patient has plasma virus fully suppressed looms over structured natural conception initiatives for discordant heterosexual couples wanting offspring [1, 7, 8]. Unfortunately, an absolute zero risk for a coital act seems theoretically unattainable, given the limitations of current interventions, since elimination of cellassociated HIV is not yet achievable [9]. Integrated proviral DNA lies dormant in compartmentalized cellular reservoirs, prominently including the neurological and genitourinary compartments. When HIV-harboring cells within a compartment are stimulated, site-specific viral blips occur irrespective of systemic events in blood and elsewhere. Restricted by their specific mechanism of action, drugs targeting isolated intracellular steps in the preintegration viral life cycle cannot interfere with release of virus during the first ensuing cycle after activation [10]. Even when pregnancy is the goal, unprotected intercourse should be avoided in the presence of recognized sexually transmitted diseases or other genitourinary infections; however, self-limited productive HIV infection is likely more often triggered by subclinical and, thus, unsuspected inflammation (such as asymptomatic shedding of herpesviruses) [5, 6, 11, 12]. The very small residual risk of HIV transmission associated with structured natural conception may be acceptable to qualifying and well-informed couples (especially when other options are unavailable or impractical), but the ultimate decision maker must always be the unharassed female partner [13–15].

Role of Baseline HIV-1 DNA Level in Highly-Experienced Patients Receiving Raltegravir, Etravirine and Darunavir/Ritonavir Regimen (ANRS139 TRIO Trial)

ObjectiveIn the ANRS 139 TRIO trial, the use of 3 new active drugs (raltegravir, etravirine, and darunavir/ritonavir), resulted in a potent and sustained inhibition of viral replication in multidrug-resistant treatment-experienced patients. The aim of this virological sub-study of the ANRS 139 TRIO trial was to assess: (i) the evolution of HIV-1 DNA over the first year; and (ii) the association between baseline HIV-1 DNA and virological outcome.MethodsAmong the 103 HIV-1-infected patients included in the ANRS-139 TRIO trial, HIV-1 DNA specimens were available for 92, 84, 88, and 83 patients at Week (W)0, W12, W24, and W48, respectively. Quantification of total HIV-1 DNA was performed by using the commercial kit “Generic HIV DNA Cell” (Biocentric, Bandol, France).ResultsBaseline median HIV-1 DNA of patients displaying virological success (n = 61), viral blip (n = 20), and virological failure (n = 11) were 2.34 log10 copies/106 PBMC (IQR = 2.15–2.66), 2.42 (IQR = 2.12–2.48), and 2.68 (IQR = 2.46–2.83), respectively. Although not statistically significant, patients exhibiting virological success or viral blip had a tendency to display lower baseline HIV-1 DNA than patients experiencing virological failure (P = 0.06). Median decrease of HIV-1 DNA between baseline and W48 was -0.13 log10 copies/106 PBMC (IQR = -0.34 to +0.10), mainly explained by the evolution from W0 to W4. No more changes were observed in the W4-W48 period.ConclusionsIn highly-experienced multidrug-resistant patients, HIV-1 DNA slightly decreased during the first month and then remained stable during the first year of highly potent antiretroviral regimen. In this population, baseline HIV-1 DNA might help to better predict the virological response and to tailor clinical therapeutic management as more aggressive therapeutic choices in patients with higher baseline HIV-1 DNA.

Patterns and Causes of Suboptimal Response to Tenofovir-Based Therapy in Individuals Coinfected With HIV and Hepatitis B Virus

Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART). One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA. Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified. Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.