Risk Of Virologic Rebound Research Articles

Association between markers of hepatitis B virus infection and risk of virological rebound in people with HIV receiving antiretroviral therapy.

The aim of this analysis was to investigate the impact of hepatitis B virus (HBV) coinfection on the risk of HIV viral rebound (VR) after achieving suppression for the first time following initiation of antiretroviral therapy (ART) in the real-world setting. Patients living with HIV (PLWH) who were enrolled in the ICONA Foundation Study cohort and achieved viral suppression ≤50 copies/mL for the first time after starting ART were prospectively evaluated and divided in three exposure groups according to serology test results: (a) HIV-monoinfected; (b) HIV-positive/HBcAb-positive/HBsAg-negative; (c) HIV-positive/HBsAg-positive. The occurrence of VR, defined as two consecutive HIV-RNA values >50 copies/mL after achieving viral suppression for the first time (baseline), was investigated. Standard survival analysis by means of Kaplan-Meier curves and Cox regression analysis with the serology exposure fitted as a time-fixed covariate measured at baseline was employed after controlling for key confounding factors. Of a total of 5657 patients included, 4090 (72%) were HIV-monoinfected, 1342 (23.7%)were HBcAb-positive, and 225 (3.9%) were HbsAg-positive coinfected. Overall, 654 (11.5%) PLWH experienced VR > 50 copies/mL during follow-up. After controlling for all sources of measured confounding, coinfected PLWH showed an increased risk of experiencing VR compared with those who were HIV-monoinfected. In particular, the strongest associations were seen for the HIV/HBsAg-positive participants [adjusted hazard ratio (aHR) = 1.56, 95% confidence interval (CI): 1.03-2.38, p = 0.037] but an excess of risk was also seen in those who were HIV-positive/HBcAb-positive/HBsAg-negative (aHR = 1.25, 95% CI: 1.00-1.55, p = 0.047). Coinfection with HBV seems to have an impact on the probability of maintaining HIV viral suppression achieved for the first time after ART initiation. Of note, even PLWH positive for HBcAb, a marker of inactive HBV infection, appeared to be at higher risk of VR compared with those who were HIV-monoinfected and their HIV-RNA should be carefully monitored.

Very high pre-therapy viral load is a predictor of virological rebound in HIV-1-infected patients starting a modern first-line regimen.

Pre-cART (combined antiretroviral therapy) plasma viral load >500,000 copies/ml has been associated with a lower probability of achieving virological suppression, while few data about its role on maintenance of virological suppression are available. In this study we aimed to clarify whether high levels of pre-cART viraemia are associated with virological rebound (VR) after virological suppression. HIV-infected individuals who achieved virological suppression after first-line cART were included. VR was defined as the first of two consecutive viraemia >50 copies/ml (VR50) or, in an alternative analysis, >200 copies/ml (VR200). The impact of pre-cART viraemia on the risk of VR was evaluated by survival analyses. Among 5,766 patients included, 59.2%, 31.4%, 5.2% and 4.2% had pre-cART viraemia ≤100,000, 100,001-500,000, 500,001-1,000,000 and >1,000,000 copies/ml, respectively. Patients with pre-cART viraemia levels >1,000,000 copies/ml had the highest probability of VR (>1,000,000; 500,000-1,000,000; 100,000-500,000; <100,000 copies/ml; VR50: 28.4%; 24.3%; 17.6%; 13.8%, P<0.0001; VR200: 14.4%; 11.1%; 7.2%; 7.6%; P=0.009). By Cox multivariable analyses, patients with pre-cART viraemia >500,000 and >1,000,000 copies/ml showed a significantly higher risk of VR regardless of the VR end point used. No difference in the risk of VR was found between patients with pre-cART viraemia ranging 500,000-1,000,000 copies/ml and those with pre-cART viraemia >1,000,000 copies/ml, regardless of the VR end point used. Pre-cART plasma viral load levels >500,000 copies/ml can identify fragile patients with poorer chance of maintaining virological control after an initial response. An effort in defining effective treatment strategies is mandatory for these patients that remain difficult to treat.

Duration of Antiretroviral Therapy Adherence Interruption Is Associated With Risk of Virologic Rebound as Determined by Real-Time Adherence Monitoring in Rural Uganda.

Antiretroviral therapy (ART) adherence interruptions have been associated with viral rebound; however, the true risk is unknown because HIV RNA has never been measured during ongoing interruptions. The Uganda AIDS Rural Treatment Outcomes Study is an observational longitudinal cohort of adults initiating ART. We monitored adherence with the device that wirelessly transmits records of device openings, and routinely assessed HIV RNA quarterly. When lapses of 48+ hours between device openings were detected, we made unannounced visits to participants to investigate the cause and assess HIV RNA. Generalized estimating equation logistic regressions were used to assess factors associated with viral rebound. We followed 479 participants (median: 25 months per participant). Most were women (72%), median age was 36 years, median pre-ART CD4 count was 198 cells per microliter, median pre-ART HIV RNA level was 5.0 log10 copies per milliliter, and median duration of prior viral suppression was 13 months. A total of 587 adherence interruptions followed confirmed prior viral suppression, of which 13 (2%) had detectable viral rebound. Viral rebound was associated with duration of adherence interruption (odds ratio: 1.25 for each day beyond 48 hours; P = 0.007) and 30-day adherence before the interruption (odds ratio: 0.73; P = 0.02). This article is the first demonstration of HIV RNA rebound during adherence interruptions objectively measured in real time. Odds of viral rebound increased by 25% with each day beyond 48 hours. Real-time adherence monitoring was feasible in a sub-Saharan African setting. Further research should assess the potential for real-time adherence interventions to sustain adherence to affordable first-line regimens.

HIV DNA loads, plasma residual viraemia and risk of virological rebound in heavily treated, virologically suppressed HIV-infected patients

In this single-centre, retrospective study, we analyzed data of 194 patients receiving antiretroviral therapy with <50 human immunodeficiency virus (HIV) RNA copies/mL in plasma and 318 HIV RNA/DNA paired samples. By kinetic polymerase chain reaction (kPCR) molecular system analysis, 104 (54%) subjects had undetectable HIV RNA and 90 (46%) had residual viraemia. Median (interquartile range) HIV DNA load was 780 (380–1930) copies/106 peripheral blood lymphocytes (PBL), and HIV DNA loads were independently associated with residual viraemia (p 0.002). Virological rebound occurred in 29/194 (15%) patients over a median (interquartile range) follow-up of 17.5 (13.5–31.5) months. Residual viraemia (p 0.002), but not HIV DNA load, was independently associated with virological rebound.

Plasma HIV-1 RNA Detection Below 50 Copies/mL and Risk of Virologic Rebound in Patients Receiving Highly Active Antiretroviral Therapy

Plasma human immunodeficiency virus type 1 (HIV-1) RNA suppression <50 copies/mL is regarded as the optimal outcome of highly active antiretroviral therapy (HAART). Current viral load (VL) assays show increased sensitivity, but the significance of RNA detection <50 copies/mL is unclear. This study investigated the virologic outcomes of 1247 patients with VL <50 copies/mL at an arbitrary time point during HAART (= T0), according to whether the actual, unreported (T0)VL was 40-49 copies/mL, RNA detected <40 copies/mL (RNA(+)), or RNA not detected (RNA(-)), as measured by the Abbott Real Time assay. Predictors of rebound >50 and >400 copies/mL over 12 months following T0 were analyzed with Cox proportional hazards models incorporating the (T0)VL and demographic and clinical data. Rebound rates >50 copies/mL were 34.2% for (T0)VL 40-49 copies/mL, 11.3% for RNA(+), and 4.0% for RNA(-); rebound rates >400 copies/mL were 13.0%, 3.8%, and 1.2%, respectively. The adjusted hazard ratios for rebound >50 copies/mL were 4.67 (95% confidence interval, 2.91-7.47; P < .0001) and 1.97 (1.25-3.11; P < .0001) with (T0)VL 40-49 copies/mL and RNA(+), respectively, relative to RNA(-), and 6.91 (2.90-16.47; P < .0001) and 2.88 (1.24-6.69; P < .0001), respectively, for rebound >400 copies/mL. The association was independent of adherence levels. In treated patients monitored by RealTime, a VL of 40-49 copies/mL and, to a lesser extent, RNA detection <40 copies/mL predict rebound >50 and >400 copies/mL independently of other recognized determinants. The goal of HAART may need to be revised to a lower cutoff than 50 copies/mL.

Physical and Psychological Symptoms and Risk of Virologic Rebound Among Patients With Virologic Suppression on Antiretroviral Therapy

We examined the association of self-reported physical and psychological symptoms with subsequent virologic rebound among patients with viral suppression on combination antiretroviral therapy (cART). We included 188 HIV patients from a routine London clinic, who completed a questionnaire on heath/treatment issues in 2005, and were on cART, with viral load (VL) < 50 c/mL. Symptom measures were based on the Memorial Symptom Assessment Scale Short Form, and additional questions: (1) physical symptom score; (2) psychological symptom score; (3) global symptom score; (4) total number of symptoms; (5) anxiety/depression; and (6) suicidal thoughts. Associations with time to (1) VL > 200 c/mL and (2) VL > 50 c/mL were assessed, considering each symptom measure separately. Of 188 patients, 22 experienced VL > 200 c/mL and 46 experienced VL > 50 c/mL (median follow-up: 2.2 years). Risk of VL > 200 c/mL was increased 4- to 5-fold for the highest versus lowest tertiles for the symptom scores (measures 1-3) and total number of symptoms (measure 4), and almost 4-fold for anxiety/depression (measure 5). Associations remained after adjustment for demographic and treatment-related factors (P = 0.006 to P = 0.050, measures 1-5), and were little attenuated after additional adjustment for subject-reported nonadherence (P = 0.011 to P = 0.072). There was a weaker, nonsignificant association with suicidal thoughts (measure 6). For risk of VL > 50 c/mL, all symptom measures were positively associated with rebound risk (P = 0.019 to P = 0.053, measures 1-6, adjusted for demographic and treatment-related factors; P = 0.022 to P = 0.084 after additional adjustment for nonadherence). Among patients on successful cART, physical and psychological symptoms were strongly predictive of viral rebound. Simple symptom inquiry may be valuable in the clinical setting to identify patients at risk of treatment failure, and provide opportunity for intervention.

Le voyageur infecté par le VIH : risques infectieux et prévention

Patients with human immunodeficient virus (HIV) must make special preparations before traveling. They have a higher risk of infection than the general population. They are more likely to develop malaria and the clinical episodes will be more severe, particularly in pregnant women. Prescriptions for malaria prophylaxis and treatment must take into account their interactions with antiretroviral drugs. Vaccination decisions require consideration of the risk and severity of the vaccine preventable diseases in the destination area, the nature of the vaccine, the patient's immune status, and the risk of virological rebound as a consequence of vaccination. Some countries have entry restriction for travelers with HIV. Special precautions may be necessary for transporting and storing antiretroviral medications.

Predictors of Residual Viremia in HIV‐Infected Patients Successfully Treated with Efavirenz and Lamivudine plus either Tenofovir or Stavudine

In human immunodeficiency virus (HIV)-infected patients successfully treated with highly active antiretroviral therapy (HAART), a low level of HIV RNA persists in plasma at steady state for years and varies among patients. To understand predictors of residual viremia, we measured HIV RNA levels <50 copies/mL in patients after 1 year of treatment with efavirenz and lamivudine plus either tenofovir disoproxil fumarate (n=55) or stavudine (n=45), by use of an HIV RNA assay with a limit of detection of 2.5 copies/mL. The mean posttreatment HIV RNA levels were 0.58 log(10) copies/mL (3.8 copies/mL) in the tenofovir arm and 0.61 log(10)copies/mL (4.1 copies/mL) in the stavudine arm (P=.24). Forty-seven percent of patients receiving tenofovir, compared with 29% of patients receiving stavudine, had undetectable residual viremia (P=.07). In multivariate analyses, we found that lower baseline HIV RNA levels in plasma, lower HIV DNA levels in peripheral blood mononuclear cells, and inclusion in the tenofovir arm each independently predicted undetectable residual viremia (P<.05). However, a level of residual viremia <50 copies/mL was not associated with CD4 cell count changes or risk of virologic rebound through 72 weeks of follow-up.