Purpose: Nucleoside reverse transcriptase inhibitors (NRTIs) are associated with mitochondrial toxicities ranging from asymptomatic hyperlactatemia to fatal lactic acidosis. It is uncertain whether mild clinical symptoms predict hyperlactatemia and the need to consider changes in antiretroviral therapy. This cross-sectional study evaluated whether an association exists between mild symptoms and lactate levels. Method: HIV-positive patients on NRTIs attending routine clinic visits were surveyed about symptoms associated with hyperlactatemia. Symptom severity was quantified using Likert scales, and the sum was converted into a symptom score ranging from 0 to 30. Tourniquet-free blood specimens were collected simultaneously to measure serum lactate. Symptom scores were compared between patients with normal and elevated lactates. Results: 284 individuals were included. The most common NRTIs used included lamivudine (79%), zidovudine (50%), abacavir (39%), and stavudine (24%). Twenty-two patients (8%) had increased lactates (mean = 2.7 mmol/L; range, 2.1-4.5 mmol/L), while 262 patients (92%) had normal lactates (mean = 1.2 mmol/L, range, 0.1-2.0 mmol/L). Median symptom scores were similar between groups (3 vs. 2, p = .23). Spearman's correlation coefficient for lactate and symptom score was 0.07 (p = .22). Conclusions: Mild symptoms did not correlate with lactate levels, and symptoms alone should not trigger clinicians to measure serum lactates and stop NRTIs if the levels are elevated.

Purpose: The purpose of this study was to evaluate the short-term effects (up to 6 months) of tenofovir disoproxil fumarate (DF) use on renal function in patients being treated for HIV-1 infection. Method: The charts of 447 HIV-1-infected patients who received at least three months of tenofovir DF treatment were reviewed. Data collected included demographics, concurrent antiretrovirals, other concurrent medications, CD4 counts and HIV-1 viral loads, and serum creatinine values while on tenofovir DF. Data collection was truncated at 6 months. Results: Baseline serum creatinine (SCr) was 1.0 mg/dL, with a calculated creatinine clearance (CLCr) of 95.2 mL/min (using the Cockroft-Gault equation). There was no significant change in SCr or CLCr at 12 weeks (1.1 mg/dL and 92.7 mL/min, respectively) or 24 weeks (1.1 mg/dL and 92.9 mL/min, respectively). All three patients with grade 2 increases in SCr had other medical reasons for an increased SCr (one patient each had indinavir-associated nephrolithiasis, lactic acidosis, and pancreatitis). No patients experienced any complications from these increases in SCr. Conclusion: Increases in SCr and CLCr within the first 6 months of tenofovir DF therapy were rare. Although no clinical nephrotoxicity was observed, continued observation of renal function is warranted in patients predisposed to renal impairment.

Purpose: The purpose of this study was to evaluate the short-term effects (up to 6 months) of tenofovir disoproxil fumarate (DF) use on renal function in patients being treated for HIV-1 infection. Method: The charts of 447 HIV-1-infected patients who received at least three months of tenofovir DF treatment were reviewed. Data collected included demographics, concurrent antiretrovirals, other concurrent medications, CD4 counts and HIV-1 viral loads, and serum creatinine values while on tenofovir DF. Data collection was truncated at 6 months. Results: Baseline serum creatinine (SCr) was 1.0 mg/dL, with a calculated creatinine clearance (CLCr) of 95.2 mL/min (using the Cockroft-Gault equation). There was no significant change in SCr or CLCr at 12 weeks (1.1 mg/dL and 92.7 mL/min, respectively) or 24 weeks (1.1 mg/dL and 92.9 mL/min, respectively). All three patients with grade 2 increases in SCr had other medical reasons for an increased SCr (one patient each had indinavir-associated nephrolithiasis, lactic acidosis, and pancreatitis). No patients experienced any complications from these increases in SCr. Conclusion: Increases in SCr and CLCr within the first 6 months of tenofovir DF therapy were rare. Although no clinical nephrotoxicity was observed, continued observation of renal function is warranted in patients predisposed to renal impairment.

Method: Infectious complications were assessed in 25 HIV-HCV coinfected patients receiving 29 courses of HCV therapy (786 person-weeks). Results: The infection rate (1.3 infections/100 person-weeks) was similar when compared to the rate in HIV-negative patients. HIV status and neutrophil nadir did not predict infection risk or rate. Conclusion: Interferon dose reduction and/or G-CSF in HCVtreated HIV patients with neutropenia are not justified.

Purpose: To assess the safety and efficacy of a 4-drug, 3-tablet, once-daily (qd) regimen consisting of abacavir/lamivudine/zidovudine (ABC/3TC/ZDV; 2 tablets) and tenofovir (TDF) in antiretroviral-naïve patients with plasma HIV-1 RNA ⩾30,000 copies/mL at 48 weeks. Method: All participants received ABC/3TC/ZDV (300/150/300 mg) and TDF (300 mg) qd in this pilot, open-label, multicenter study. Intent-to-treat (ITT) analyses were conducted to evaluate virologic and immunologic efficacy. Results: Of the 123 participants enrolled, 52 (42%) prematurely discontinued study for adverse events (14), were lost to follow-up (13), had virologic nonresponse (12), and withdrew for other reasons (13). At week 48, by ITT missing=failure analysis, 41% (51/123) and 51% (63/123) of participants had plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; by ITT-observed analysis, 75% (51/68) and 93% (63/68) had plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; 11% (14/123) met virologic nonresponse criteria. Median week 48 change in CD4+ cell count from baseline was +127 cells/mm³. Median week 48 changes from baseline for fasting lipids were as follows: cholesterol (–9 mg/dL), HDL (+1 mg/dL), LDL (–9 mg/dL), and triglycerides (–4 mg/dL). Conclusion: A high rate of premature discontinuations contributed to the overall suboptimal virologic response to ABC/3TC/ZDV+TDF qd; however, the regimen was not associated with high rates of virologic failure previously observed with TDF+ABC/3TC.

Background: Regimens based on ritonavir-boosted protease inhibitors (PI/r) are often used as rescue interventions. It is unclear whether significant differences exist between distinct PI/r. Method: All HIV+ patients who had experienced PI failure at two HIV clinics and were rescued with a regimen based on saquinavir (SQV)/r 1000/100 mg bid, indinavir (IDV)/r 800/100 mg bid, lopinavir (LPV)/r 400/100 mg bid, amprenavir (APV)/r 600/100 mg bid, atazanavir (ATV)/r 300/100 mg qd, or tipranavir (TPV)/r 500/200 mg bid were retrospectively examined. A significant virological response (VR) was defined as >1 log reduction in plasma HIV-RNA or to <50 copies/mL at week 24. Results: A total of 389 patients were included in the analysis: 139 on SQV/r, 35 on IDV/r, 129 on LPV/r, 35 on APV/r, 29 on ATV/r, and 22 on TPV/r. No significant differences in HIV-RNA and CD4 counts at baseline were recognized between groups. In a multivariate analysis, only the total number of protease resistance mutations was associated with a lower VR (odds ratio [OR] = 0.77, 95% CI 0.68–0.87, p .001). The presence of <5 or ⩾5 protease resistance mutations at baseline was the best threshold to discriminate the achievement of VR in any treatment group. In an intent-to-treat analysis, for individuals with ⩾5 protease resistance mutations, the rates of VR were 64% with TPV/r, 47% with LPV/r, 46% with SQV/r, 33% with ATV/r, 25% with IDV/r, and 16% with APV/r. Adverse events leading to treatment withdrawal occurred more frequently using IDV/r (22.8%) than others (p = .03). Conclusion: The rate of VR in salvage therapy using PI/r-based regimens is relatively high in PI-experienced patients. The efficacy is greatly influenced by the number of baseline protease resistance mutations; 5 mutations is the best threshold to predict the chances of VR to any PI/r-based regimen.

Purpose: Adverse effects are important determinants of quality of life (QOL) during highly active antiretroviral therapy (HAART). The PLATO study investigated the association between changes in patient-reported outcomes including QOL and substitution with lopinavir/ritonavir in patients experiencing side effects (SEs). Method: HIV–1–infected participants (N = 849) with undetectable viral load experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized to immediate (baseline) or deferred (week 4) substitution with lopinavir/ritonavir soft-gel capsules 400/100 mg bid. The primary endpoint was change in the total score from the AIDS Clinical Trials Group (ACTG) Symptoms Distress Module (ASDM), supplemented with two items for nephrolithiasis. Secondary endpoints included Medical Outcomes Study (MOS)-HIV scores and Center for Epidemiologic Studies–Depression (CES-D) scores. Results: Immediate substitution resulted in improved ASDM total score at week 4 compared with deferred substitution (p <.001) and significant improvements in all MOS-HIV domains, while significant improvement was observed in CES-D scores at week 8. Primary SEs resolved at week 8 in 65% of participants in the immediate substitution group. Suppression of HIV-1 was maintained. Treatment was well-tolerated and associated with elevations in cholesterol and triglycerides. Conclusion: Substitution with LPV/r improved patient-reported outcomes including QOL in patients experiencing Grade-2 SEs, while maintaining viral suppression.

Objectives: To analyze the incidence of severe liver events in HIV patients treated with lopinavir/ritonavir and the role of coinfection in the development of this toxicity. Method: This was a retrospective, multicenter, cohort study of all HIV-positive patients who started a regimen of HAART that included lopinavir/ritonavir (LPV/r). The main outcome variable was the emergence of a severe liver event, defined as decompensation of pre-existing chronic liver disease and grade 3–4 hypertransaminasemia (HT), that is, plasma AST or ALT values >5 times above the upper limit of normality, if baseline levels were normal, or >3.5 times the baseline values when they were abnormal. Results: 388 HIV-infected patients were included, with a median follow-up of 25.6 months. Coinfection with HCV was present in 61% of the patients and with HBV in 6.7%. There were 6 cases of severe liver events, all involving patients who were coinfected with HCV and all within the first 6 months. This represents 0.72 events per 100 patient-years (95% confidence interval [CI] 02.98) and 1.21 events per 100 patient-years (95% CI 0.60–5.86) in coinfected patients. The only factors associated with severe liver events at 6 months were baseline HT and HCV coinfection. Conclusion: The incidence of severe hepatic events in HIV-positive patients receiving a HAART regimen including LPV/r was very low, even in coinfected patients. HCV coinfection and baseline HT were the only factors associated with severe liver events. LPV/r can be considered a safe and well-tolerated option in HIV patients with hepatotropic virus coinfections.

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This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.