Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort.

BACKGROUND: Despite sparse efficacy data, tenofovir-emtricitabine or tenofovir-lamivudine plus nevirapine is used in many resource-constrained settings. METHODS: This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir-emtricitabine or lamivudine (tenofovir group) or zidovudine-lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. RESULTS: A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03-1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40-.63) and increasing age (HR, 0.98; 95% CI, .97-.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. CONCLUSIONS: Compared with zidovudine-lamivudine, the use of tenofovir-lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection.

Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings.

BACKGROUND: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria. METHODS: We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria. RESULTS: A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001). CONCLUSIONS: Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.

Potential for false-positive HIV test results using rapid HIV testing algorithms.

Background: In order to scale up access to HIV counselling and testing in Nigeria, an HIV diagnostic algorithm based on rapid testing was adopted. However, there was the need to further evaluate the testing strategy in order to better assess its performance, because of the potential for false positivity. Objectives: The objective of this study was to compare positive HIV test results obtained from the approved rapid testing algorithm with results from western blot tests performed on samples from the same patient. Methodology: A retrospective review was conducted of HIV screening and confirmatory results for patients seen between 2007 and 2008. Rapid test and western blot results were extracted and compared for concordance. Discordant results were further reviewed using a combination of HIV-1 RNA viral load and CD4+ cell count test results and clinical presentation from medical records. Results: Analysis of 2228 western blot results showed that 98.3% (n = 2191) were positive for HIV-1, 0.4% (n = 8) were positive for HIV-2 and 0.3% (n = 7) were dual infections (positive for both HIV-1 and HIV-2); 0.6% (n = 13) were indeterminate and 0.4% (n = 9) were negative. Further investigation of the 13 indeterminate results showed nine to be HIV-1 positive and four to be HIV-negative, for a total of 13 negative results. The positive predictive value of the HIV counselling and testing algorithm was 99.4%. Conclusion: Using the rapid testing algorithm alone, false positives were detected. Therefore, effective measures such as training and retraining of staff should be prioritised in order to minimise false-positive diagnoses and the associated potential for long-term psychological and financial impact on the patients.

Comparison of the COBAS/Ampliprep Taqman and Amplicor HIV-1 monitor tests in Lagos, Nigeria.

BACKGROUND: The use of real-time Polymerase chain reaction (PCR) technology options is increasing in resource-limited settings because they are faster, improve assay sensitivity, have higher throughput, larger dynamic ranges and reduced rates of contamination. In 2010, UNAIDS ranked Nigeria as the second highest population of people living with HIV and AIDS (2.98 million people) in the world. OBJECTIVE: The objective of this study was to compare the analytical performances of the Amplicor HIV-1 Monitor (version 1.5) and the COBAS Ampliprep/Taqman (version 2.0) used in monitoring HIV disease progression in HIV-infected individuals. METHOD: In a cross-sectional study, HIV-1 RNA values obtained with the Amplicor HIV-1 monitor version 1.5 were compared with those of the COBAS/Ampliprep TaqMan HIV-1 version 2.0 in a routine clinical setting. Between May and November 2011, 176 plasma samples collected were analysed in parallel using both techniques. Data analysis was done using statgraphics Centurion XVI and Medcalc version 12.0. RESULT: The correlation coefficient for the two assays was 0.83 and the level of agreement using a Bland-Altman plot was 94.2%. CONCLUSION: These findings suggest that the results from the two methods were comparable, hence the COBAS/Ampliprep Taqman version 2.0 is recommended for high-volume laboratories.