High Rate of HIV Re-suppression After Viral Failure on First Line Antiretroviral Therapy in the Absence of Switch to Second Line.

In a randomised comparison of nevirapine or abacavir with zidovudine + lamivudine, routine viral load monitoring was not performed yet 27% of individuals with viral failure at w48 re-suppressed by w96 without switching. This supports WHO recommendations that suspected viral failure should trigger adherence counselling and repeat measurement before considering treatment switch

Virological outcomes of second-line protease inhibitor-based treatment for human immunodeficiency virus type 1 in a high-prevalence rural South African setting: a competing-risks prospective cohort analysis

Background. Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. Methods. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up. Results. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001). Conclusions. Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed

Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

ABSTRACT: BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/mL) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n=701) and 70% (n=369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/mL). Risk factors for virological failure (>1,000 copies/mL) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSIONS: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy

Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa.

OBJECTIVES: To evaluate virologic response up to 48 weeks, and emergence of HIV-1 resistance mutations at 24 weeks, in therapy-naive adults initiating zidovudine/lamivudine/tenofovir DF. DESIGN: : A cohort within the DART trial. METHODS: Plasma HIV-1 RNA was assayed in 300 adults with baseline CD4 cell count 1000 copies/ml at 24 weeks were sequenced in the pol region. RESULTS: Median baseline CD4 cell count was 101 cells/mul and HIV-1 RNA 279,910 copies/ml (mean, 5.4 log10). At 48 weeks, 61% (165/272) had HIV-1 RNA 1000 copies/ml (6 and 17% > 10 000 copies/ml), and mean CD4 cell count increases were 103 and 127 cells/mul, respectively. Higher baseline CD4 cell count was the most important predictor of virological suppression at 48 weeks, with little effect of baseline viral load. Eighteen of 20 genotypes from week 24 samples with HIV-1 RNA > 1000 copies/ml showed key resistance mutations in reverse transcriptase. Fourteen had M184V [10 with one to four additional nucleoside analogue mutations (NAMs)]; one had three NAMs only; and the remaining three had K65R. One participant with M184V had major non-nucleoside reverse transcriptase inhibitor-associated mutations, despite no disclosed treatment with this class. CONCLUSION: Zidovudine/lamivudine/tenofovir has good virological efficacy in advanced HIV disease. In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often

Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa.

OBJECTIVES: To evaluate virologic response up to 48 weeks, and emergence of HIV-1 resistance mutations at 24 weeks, in therapy-naive adults initiating zidovudine/lamivudine/tenofovir DF. DESIGN: : A cohort within the DART trial. METHODS: Plasma HIV-1 RNA was assayed in 300 adults with baseline CD4 cell count &lt; 200 cells/mul from sites in Uganda and Zimbabwe using the Roche Amplicor assay v1.5. Samples with HIV-1 RNA &gt; 1000 copies/ml at 24 weeks were sequenced in the pol region. RESULTS: Median baseline CD4 cell count was 101 cells/mul and HIV-1 RNA 279,910 copies/ml (mean, 5.4 log10). At 48 weeks, 61% (165/272) had HIV-1 RNA &lt; 50 and 72% (196/272) &lt; 400 copies/ml, compared with 59% (167/281) and 79% (221/281) at 24 weeks. At 24 and 48 weeks, 15 and 24% respectively had HIV-1 RNA &gt; 1000 copies/ml (6 and 17% &gt; 10 000 copies/ml), and mean CD4 cell count increases were 103 and 127 cells/mul, respectively. Higher baseline CD4 cell count was the most important predictor of virological suppression at 48 weeks, with little effect of baseline viral load. Eighteen of 20 genotypes from week 24 samples with HIV-1 RNA &gt; 1000 copies/ml showed key resistance mutations in reverse transcriptase. Fourteen had M184V [10 with one to four additional nucleoside analogue mutations (NAMs)]; one had three NAMs only; and the remaining three had K65R. One participant with M184V had major non-nucleoside reverse transcriptase inhibitor-associated mutations, despite no disclosed treatment with this class. CONCLUSION: Zidovudine/lamivudine/tenofovir has good virological efficacy in advanced HIV disease. In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often

High rate of HIV resuppression after viral failure on first-line antiretroviral therapy in the absence of switch to second-line therapy.

In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered