Does region of origin influence the timing and outcome of first-line antiretroviral therapy in France?

OBJECTIVES: The aim of the study was to assess whether the timing of combination antiretroviral therapy (cART) initiation, the choice of cART and virological response differ in migrants versus European natives in the north and east of Paris area, after dissemination of French recommendations for universal treatment. METHODS: Antiretroviral therapy-naïve HIV-1-infected adults with at least two follow-up visits at one of 15 participating centres between 1 January 2014 and 31 March 2015 were included in the study. Factors associated with cART initiation before 31 March 2015, with protease inhibitor (PI)-containing cART among individuals initiating cART, and with 1-year virological success after cART initiation were assessed using multivariable logistic regression models. Sex, age, region of origin [Western Europe, sub-Saharan Africa (SSA) or other], HIV transmission group, baseline AIDS status, CD4 cell count and plasma viral load (VL), and hepatitis B and/or C virus infection were considered in the analyses. RESULTS: Among 912 individuals, only 584 (64%) started cART during the study period. After adjustment, migrants from SSA were half as likely to initiate cART and to have a subsequent virological response compared with individuals from Western Europe [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.82; and aOR 0.52; 95% CI 0.28-0.98, respectively]. PI-containing cART was more frequently prescribed in migrants from SSA, in people with lower CD4 cell counts and in people with higher VL. CONCLUSIONS: Even in the context of universal cART recommendations and of free access to care, migrants from SSA still have delayed access to cART and a lower virological response. Efforts are still necessary to provide immediate cART to all people living with HIV.

Recovery of fat following a switch to nucleoside reverse transcriptase inhibitor-sparing therapy in patients with lipoatrophy: results from the 96-week randomized ANRS 108 NoNuke Trial.

OBJECTIVES: To evaluate the impact on peripheral fat tissue of a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen in lipoatrophic HIV-1 infected patients. METHODS: This 96-week prospective, randomized study compared lipoatrophic patients switched to an NRTI-sparing regimen with patients remaining on an NRTI-containing regimen. The primary endpoint was the change in thigh subcutaneous fat tissue volume between baseline and week 48, as assessed by computerized tomography. RESULTS: One hundred patients were included, 50 in each arm. At baseline, patients had been on highly active antiretroviral therapy (HAART) for a median time of 6.6 years (4.9-9.7); 71% of the patients had received thymidine analogues [stavudine (37%), zidovudine (34%)]. The mean change in fat volume between baseline and week 48 significantly favoured the NRTI-sparing arm over the NRTI-maintaining arm in the intent-to-treat analysis, with a last-observation-carried-forward approach [+34 cm(3); 95% confidence interval (CI) 5-63 cm(3); P=0.002]. This was confirmed in the intent-to-treat analysis of available data, with a mean difference of +109 cm(3) (95% CI 34-185 cm(3)) at week 96 (n=53; P=0.001). This corresponded to increases of 12 and 30% in fat volume at weeks 48 and 96, respectively, in the NRTI-sparing arm. CONCLUSIONS: Switching from an effective NRTI-containing regimen to an NRTI-sparing regimen preserves immunovirological status and increases subcutaneous fat volume at weeks 48 and 96.

Pharmacokinetics of emtricitabine, didanosine and efavirenz administered once-daily for the treatment of HIV-infected adults (pharmacokinetic substudy of the ANRS 091 trial).

OBJECTIVE: This study was conducted to investigate the pharmacokinetics of emtricitabine (FTC), didanosine (ddI), and efavirenz (EFV) when administered in a once-daily combination. METHODS: Nine antiretroviral-naïve HIV-infected adults who received FTC [200 mg once a day (q.d.)], ddI (400 mg q.d. if > or =60 kg; 250 mg q.d. if <60 kg) and EFV (600 mg q.d.) were studied. The following pharmacokinetic (PK) parameters were determined over 24 h at steady-state after 4 weeks of treatment: area under the plasma concentration vs. time curve (AUC(0-24 h)), maximum (Cmax) and minimum (Cmin) plasma concentrations, time to reach Cmax (Tmax), and the elimination half-life (t(1/2)). EFV plasma concentrations were also measured during follow-up. RESULTS: Median PK parameters for FTC, ddI and EFV, respectively, were as follows. AUC(0-24 h): 7.2, 7.0 and 36.4 h x mg/L; Cmax: 1.8, 2.6 and 2.5 mg/L; Cmin: 0.04, <0.01 and 1.0 mg/L; Tmax: 1.8, 1.1 and 2.5 h; t(1/2): 7.4, 2.3, and 23.7 h. EFV plasma concentrations measured 10-13 h postdosing were higher during follow-up than during the PK study (2.57 vs. 1.19 mg/L, P<0.01). CONCLUSION: The simultaneous administration of FTC, ddI and EFV did not affect the PK parameters of FTC when compared to historical controls. EFV Cmax and Cmin were lower than expected, but the data may have been slightly underestimated in this study. High ddI AUC and Cmax were measured in these patients, and further studies are warranted to confirm this finding.

BMD is reduced in HIV-infected men irrespective of treatment.

UNLABELLED: Osteoporosis has be reported to be a complication of active antiretroviral therapy of HIV infection. We studied 148 HIV-infected men stratified according to their treatment. Our data show that these patients have an average 9% decreased BMD, irrespective of their treatment. Low body mass index and high resorption markers were associated with low bone density. INTRODUCTION: Osteoporosis has been reported in HIV-infected (HIV+) patients, and it has been suggested that it may be linked to protease-inhibitor treatments (PI). MATERIALS AND METHODS: To assess this risk and to investigate its putative link with treatments, we compared the bone density of HIV+ men, who were either receiving treatment (including PI [PI+], n = 49; without PI [PI-], n = 51) or untreated (UT, n = 48). We included 81 age-matched control HIV-negative (HIV-) males (age, 40 +/- 8 years). RESULTS: BMD adjusted for age (Z-score) was lower in the HIV+ patients at the lumbar spine (HIV+: -1.08 +/- 1.21, HIV-: -0.06 +/- 1.26, p < 0.001) and the femoral neck (HIV+: -0.39 +/- 1.05, HIV-: 0.25 +/- 0.87, p < 0.001). The prevalence of osteoporosis was 16% in HIV+ and 4% in HIV- subjects (p < 0.01). In the HIV+ subjects, the Z-score was correlated only to body mass index (r = 0.27 at lumbar spine and 0.35 at femoral neck). Untreated HIV+ patients had a negative Z-score (-0.82 +/- 1.15 for the lumbar spine), which was not different from the one of treated HIV+ patients. In the PI+ and PI- groups, the Z-score did not depend on the presence of lipodystrophy or the proportion of fat in the abdomen and legs measured by DXA. Markers of bone remodeling were measured in the 132 HIV+ and 35 HIV- subjects. Compared with controls, HIV+ patients had lower bone alkaline phosphatase and higher urinary cross-laps/Cr, which was negatively correlated with the Z-score at both the femoral neck (r = -0.22) and lumbar spine (r = -0.21). TNFalpha was increased in untreated compared with treated HIV+ subjects and was not correlated to the Z-score. CONCLUSION: Our cross-sectional study does not show any deleterious effect of the treatment but does indicate a decrease in bone density in HIV+ patients irrespective of the treatment. This low bone density is in part related to the low body weight and is associated with increased bone resorption.

[Febrile pseudotumor lesion of the arm. Atypical presentation of Shulman syndrome]]. / Lésion pseudotumorale fébrile du bras. Présentation atypique d'un syndrome de Shulman.

INTRODUCTION: The diagnostic approach when confronted with a pseudo-tumoral lesion and fever is difficult since it evokes an infectious, rheumatismal inflammatory or even systemic disease. OBSERVATION: A 39 year-old Vietnamese man was hospitalised for polyarthralgia if the arm and fever (39 degrees C). He was treated with non-steroidal anti-inflammatories, which were only partially effective. Biological examinations revealed a severe inflammatory syndrome and cytolysis three-fold higher than normal. Since the infectious, rheumatismal and immunological explorations were negative and in view of the appearance of a pseudo-tumoral inflammatory lesion of the left arm concomitant to infiltration of the underlying muscle revealed on MRI, a muscle biopsy was performed showing eosinophilic fasciitis. Diagnosis of Shulman's syndrome was made and the affection rapidly improved with corticosteroids. COMMENTS: The presentation of our patient was atypical for several reasons: his Vietnamese origin, the initial fever peak at 39 degrees C, the unilateral involvement, the severe inflammatory syndrome, the initial absence of hypereosinophilia, the visceral involvement and notably myositis are all uncommon in Shulman's syndrome. Hence, it is important to rule out its differential diagnosis from local edematous scleroderma, which does not share the same prognosis.

[A cost-effectiveness analysis of changes in therapeutic strategies in the treatment of HIV since 1996]. / Une analyse coût-efficacité du changement des schémas thérapeutiques dans le VIH depuis 1996.

The objective was to assess the cost-effectiveness ratio of HAART in the treatment of HIV infection. Two random samples were extracted from the database of the Rothschild Public Hospital, and patients were matched for age, sex and T4 cell counts: a first sample selected in 1996/97 of HAART treated patients (CAS group) and a second sample selected in 1994/95 of non-HAART treated patients (CONTROL group). Immune recovery and use of resources data were extracted and analyzed over two years for 196 included patients. Mean T4 cell count after two years was higher among CAS patients (344/mm3 vs. 234/mm3; p < 0.0001). CAS patients recorded a supplementary cost of antiretroviral treatments (+171%; p < 0.0001) balanced by savings in other drugs expenses (-62%; p = 0.0560) and in hospitalizations (-25%; NS). Overall, CAS patients presented a 15% (NS) lower medical cost than CONTROL patients.

Sexual dysfunction in 156 ambulatory HIV-infected men receiving highly active antiretroviral therapy combinations with and without protease inhibitors.

We conducted a cross-sectional study of 156 ambulatory HIV-infected homosexual or bisexual men to assess and compare the prevalence and characteristics of sexual dysfunction according to treatment combinations (group A, protease inhibitor [PI] treatment; group B, no PI treatment; and C, PI treatment interrupted >1 month previously). The study was based on a self-administered 163-item questionnaire that included a French translation of the International Index of Erectile Function, five sections of the Derogatis Sexual Functioning Inventory, and open questions. Data analysis was performed using Mann-Whitney and Kruskal-Wallis H nonparametric tests (quantitative values) and chi2 tests (qualitative values) using SPSS software (SPSS, Chicago, IL, U.S.A.). One hundred fifty-six patients completed the study. The median age +/- SD of the patients was 40.5 +/- 7.7 years, and the median CD4+ cell count +/- SD was 415 +/- 236/mm3. One hundred eleven (71%) of 156 patients reported some degree of sexual dysfunction since the beginning of their treatment (65 [71%] of 91 group A patients; 15 [65%] of 23 group B patients; and 31 [74%] of 42 group C patients), with no significant difference among the groups. Of the 111 patients, 99 (89%) reported decrease or loss of libido, 76 (68%) reported orgasmic perturbation, 96 (86%) reported erectile dysfunction, and 65 (59%) reported ejaculation perturbation, with no significant difference among the three groups. There were no significant differences among the three groups regarding the International Index of Erectile Function and Derogatis Sexual Functioning Inventory scores. These data suggest that PI-based therapy does not seem to increase sexual dysfunction in this patient population.

Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy.

HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.

Quantification of Epstein-Barr virus load in peripheral blood of human immunodeficiency virus-infected patients using real-time PCR.

Epstein-Barr virus (EBV) reactivation is more likely to occur in immunocompromised patients with subsequent higher susceptibility to EBV-associated lymphoproliferations. In contrast to transplant recipients, limited data are available concerning the EBV load in HIV-infected patients, with or without AIDS-related non-Hodgkin's lymphomas. We developed a TaqMan real-time PCR assay, allowing both the EBV genome and a cellular gene to be quantified in order to obtain a reliable normalized measurement of the EBV load in peripheral blood mononuclear cells (PBMCs). With a wide 6-log(10) quantification range and inter-assay variations of less than 24%, this quantitative PCR was sufficiently accurate and reproducible for routine follow-up. The EBV load was determined in PBMCs from 113 HIV-infected patients, 11 patients with primary HIV infection and 24 HIV-seronegative healthy controls. The rates of EBV detection were similar in the three groups. However, EBV loads were higher in the HIV-infected group (P < 0.00001) except for the patients with primary HIV infection. Unexpectedly, EBV loads were not correlated with the clinical stages of HIV infection or HIV replication, and did not depend on the degree of immunodepression, as judged by CD4+ counts. This study contributes towards the definition of the baseline EBV load during HIV infection and stresses the broad inter-individual variability of the EBV load in HIV-infected patients. Real-time PCR provides a useful tool that can be used in further longitudinal studies to assess the relevance of the EBV load to identify HIV-infected patients with a high risk of EBV-associated lymphoproliferations.

Effect of HAART on health status and hospital costs of severe HIV-infected patients: a modeling approach.

PURPOSE: The purpose of this study was to assess the impact of highly active antiretroviral therapy (HAART) on health status and hospital costs in severe HIV-infected patients who were followed in a French hospital. METHOD: The first 500 patients who received HAART, with CD4 + cell count below 250/mm(3), were considered. Evolution of the distribution of patients among different health states, including death, was modeled through a continuous time Markov model. Hospital financial charges and antiretroviral treatment costs were computed. Health states defined by both CD4 counts and viral load were used to show clinical changes in the patient population over a 14-month period after HAART initiation. The economic impact of HAART initiation was assessed using a simplified model based on CD4 counts only over two 14-month periods, before and after initiation. RESULTS: Between day 0 and month 14, the proportion of patients in the least severe state (CD4 + >100/mm(3) and viral load<500 copies/mL) increased from 1% to 50%, and the proportion with more than 100 CD4 + cells/mm(3) increased from 17% to 80%. Antiretroviral treatments amounted to Fr 2,141 per patient-month before HAART initiation and to Fr 3,093 after. Conversely, hospital charges fell from Fr 5,138 per patient-month to Fr 3,136. CONCLUSION: Our model gives a representation of the effect of HAART on (1) the improvement of patients' health status, (2) the increase of treatment costs, and (3) the reduction of hospital financial charge. Important savings in hospital charges can compensate for the extra cost associated with the initiation of HAART.

Reversible ALS-like disorder in HIV infection.

OBJECTIVE: To describe the clinical features, treatment, and outcome of six cases of HIV-1-associated ALS-like disorder. METHODS: The authors reviewed patients with HIV infection with neurologic symptoms seen over a 13-year period. Patients were identified by using the El Escorial research diagnostic criteria defining three categories of certainty for definite, probable, or possible ALS. Clinical features, EMG, CSF, serum analyses, and imaging and virological studies were assessed. RESULTS: Six patients with immunodepression (mean CD4(+) cells = 86.2/mm(3); mean age = 34 years) developed distal motor weakness mimicking a monomelic amyotrophy that subacutely progressed regionally or assumed a symmetric distribution on more than one region. EMG was characteristic of motor neuron disease with no multifocal conduction block. Causes other than HIV-1 were ruled out. The unusual rapid extension of the disease and the positive response to antiretroviral therapy suggest that ALS syndrome and HIV infection are etiologically related. HIV-1 might cause an ALS-like disorder by several mechanisms-via neuronal infection, by secretion of toxic viral substance, by inducing the immune system to secrete cytokines, or by inducing an autoimmune disease. CONCLUSION: These cases suggest that the association between some motor neuron diseases and HIV infection is not coincidental but pathogenetically related and that ALS-like disorder should be considered an HIV-related neurologic complication.

Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment.

OBJECTIVES: To demonstrate that lamivudine and zidovudine, given separately (lamivudine/zidovudine) or as a single combination tablet (Combivir), had equivalent efficacy. To evaluate the safety and antiretroviral activity of intensification with abacavir in patients treated with lamivudine/zidovudine for > or = 12 weeks. DESIGN: A 12-week, equivalence study of lamivudine/ zidovudine versus Combivir. Patients who completed this study could enter a 48-week, intensification study of Combivir plus abacavir. METHODS: In the equivalence study, treatment-naive patients were assessed for HIV-1 RNA, CD4 cell count and genotype. The same assessments plus phenotype were made in the intensification study. Serious adverse events were recorded in the equivalence study and all adverse events in the intensification study. RESULTS: Lamivudine/zidovudine (n=40) and Combivir (n=35) gave equivalent reductions in plasma HIV-1 RNA levels at week 12. An identical proportion of patients (74%) in each treatment group harboured virus with the M184V mutation after 12 weeks. Fifty-two patients entered the intensification study and 44 completed 48 weeks of treatment. At the time of intensification with abacavir, all 35 patients with evaluable isolates harboured HIV-1 containing M184V. Addition of abacavir to Combivir led to further decreases in plasma HIV-1 RNA and increases in CD4 cell counts compared with the start of intensification (P<0.001 at week 48). After 48 weeks of triple therapy, multi-nucleoside resistance mutations at codons 69 and 151 were not detected in any patients. All treatment regimens were generally well tolerated. CONCLUSION: Lamivudine/zidovudine and Combivir have equivalent antiretroviral activity over 12 weeks. Adding abacavir to Combivir can be a safe and effective therapeutic option for patients, including those harbouring virus with the M184V mutation.

Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA.

OBJECTIVE: To assess the antiviral efficacy, safety and adherence in patients switched to an abacavir-containing nucleoside reverse transcriptase inhibitor (NRTI) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease inhibitor (PI) combination. METHODS: In an open-label, multicentre study, patients receiving 2NRTI plus PI for at least 6 months, with a history of undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1 RNA < 50 copies/ml at screening, were randomly assigned to replace the PI with abacavir (n = 105) or continue the same treatment (n = 106). Clinical assessments included plasma HIV-1 RNA, chemistry, haematology, lymphocyte counts, and adverse event reports. Adherence to treatment was assessed by patient self-report. RESULTS: A significantly longer time to treatment failure was demonstrated in the abacavir arm compared with the PI arm (P = 0.03) while treatment failure was experienced by significantly more patients in the PI arm: 24 (23%) versus 12 (12%) (P = 0.03). Therapy-limiting toxicity led to treatment failure in eight versus 14 cases in the abacavir and PI arms, respectively, whereas virological rebound was the cause in four versus two cases. Significant reductions in cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed in the abacavir arm (P < 0.001 andP = 0.035, respectively). The number of patients reporting no difficulty in taking their therapy showed a marked increase from baseline in the abacavir arm. CONCLUSION: The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.

Quantification of human immunodeficiency virus type 1 proviral load by a TaqMan real-time PCR assay.

Proviral human immunodeficiency virus type 1 (HIV-1) DNA could be a useful marker for exploring viral reservoirs and monitoring antiretroviral treatment, particularly when HIV-1 RNA is undetectable in plasma. A new technique was developed to quantify proviral HIV-1 using a TaqMan real-time PCR assay. One copy of proviral HIV-1 DNA could be detected with 100% sensitivity for five copies and the assay had a range of 6 log(10). Reproducibility was evaluated in intra- and interassays using independent extractions of the 8E5 cell line harboring the HIV-1 proviral genome (coefficients of variation [CV], 13 and 27%, respectively) and peripheral blood mononuclear cells (PBMC) from a patient with a mean proviral load of 26 copies per 10(6) PBMC (CV, 46 and 56%, respectively). The median PBMC proviral load of 21 patients, measured in a cross-sectional study, was determined to be 215 copies per 10(6) PBMC (range, <10 to 8,381). In a longitudinal study, the proviral load of 15 out of 16 patients with primary infection fell significantly during 1 year of antiretroviral therapy (P = 0.004). In the remaining patient, proviral HIV-1 DNA was detectable but not quantifiable due to a point mutation at the 5' end of the TaqMan probe. No correlation was observed between proviral load and levels of CD4(+) cells or HIV-1 RNA in plasma. TaqMan PCR is sensitive and adaptable to a large series of samples. The full interest of monitoring proviral HIV-1 DNA can now be ascertained by its application to the routine monitoring of patients.

Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo-controlled trial in AIDS patients.

This phase IIa, randomised, single-blind, placebo-controlled study was conducted to determine the dose of recombinant human granulocyte colony-stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) < or = 1.0 x 10(9)/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n = 14) or one of four lenograstim arms: 150 microg/m2/d (the standard onco-haematology dose, n = 13) or 100 (n = 13), 50 (n = 15), or 25 microg/m2/d (n = 14). In all groups, the planned dose of GCV was 10 mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p = 0.05). At week 3, median ANC (x 10(9)/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 microg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 microg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 microg/m2/d group at weeks 2 (p = 0.05) and 3 (p = 0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50 microg/m2/d is suitable for the treatment of ganciclovir-induced neutropenia and is safe. These results should help the physician choose an optimal and cost-efficient regimen for patients with AIDS-related neutropenia when rHuG-CSF support is indicated.

Long-term outcome and treatment modifications in a prospective cohort of human immunodeficiency virus type 1-infected patients on triple-drug antiretroviral regimens. Triest Cohort Investigators.

We designed a cohort in order to assess the long-term effects of triple-drug antiretroviral combinations in 608 patients infected with human immunodeficiency virus type 1 (HIV-1). We recruited patients who had been previously treated with nucleoside analogues as well as treatment-naive patients who were starting triple-drug antiretroviral combinations consisting of nucleoside analogues, either alone or in combination with a protease inhibitor. After a median follow-up time of 22 months, the incidence rates of acquired immune deficiency syndrome-defining events and death were, respectively, 6.9 (95% confidence interval [CI], 5.3-8.8) and 2.9 (95% CI, 1.9-4.2) per 100 person-years. Advanced clinical stage of disease (P=.004), a low CD4(+) cell count (P=.002), and a low quality-of-life score (P=.001) at baseline were independent predictors of clinical progression. The initial triple-drug combination was modified a total of 647 times in 321 patients. The only independent predictor of treatment modification was previous exposure to a nucleoside analogue in patients who did not receive a new nucleoside analogue at inclusion (P=.001). Plasma HIV RNA values below 500 copies/mL were obtained in 88% of the treatment-naive patients and in 57% of the previously treated patients (P<.001). Compared with previously treated patients who received > or = 1 new nucleoside analogue at enrollment, previously treated patients who did not receive a new nucleoside analogue at enrollment were twice as likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.8), and the antiretroviral-naive patients were significantly less likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted OR, 0.2; 95% CI, 0.1-0.4).

Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients.

The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.