10 research outputs found
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Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria
Background: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. Methods and Findings: From 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. Conclusions: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access
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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
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Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria
Background. Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods. This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results. Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7–27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4+ cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions. The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections
Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort
Characteristics for Patients who Initiated Third-Line ART.
c<p>Results represent median (IQR) except where indicated.</p>d<p>Time from 2 L initiation, or last suppressed VL on 2 L, to genotype sample.</p
Patient Characteristics by Duration of Second-Line Treatment Failure.
a<p>Time from 2 L initiation, or last suppressed VL on 2 L, to genotype sample.</p>b<p>Numbers represent: Median (IQR) unless otherwise indicated.</p>c<p>Time from 2 L initiation to genotype sample.</p
Accumulation of Protease Mutations According to Duration of Second-Line Treatment Failure.
<p>Accumulation of Protease Mutations According to Duration of Second-Line Treatment Failure.</p
Prevalence of reverse transcriptase mutations.
<p>(A) NRTI resistance mutations; thymidine analog mutations (TAMs) are in light grey. (B) NNRTI resistance mutations; minor mutations indicated by light grey.</p