Drug Information Updates

On a monthly basis, USP DQI will supply new information on priority drugs, including antimicrobials, and new therapies that are published in authoritative medical and scientific journals or on reliable Internet sites.

July 2008 Update

Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants
Early changes in T-cell activation predict antiretroviral success in salvage therapy of HIV infection.
Differential extracellular and intracellular concentrations of zidovudine and lamivudine in semen and plasma of HIV-1-infected men
Impact on hemoglobin of starting combination antiretroviral therapy with or without zidovudine in anemic HIV-infected patients
The genotypic inhibitory quotient: a predictive factor of atazanavir response in HIV-1-infected treatment-experienced patients
Antiretroviral therapy for HIV-infected tuberculosis patients saves lives but needs to be used more frequently in Thailand
Adherence to antiretroviral therapy assessed by drug level monitoring and self-report in Cameroon
Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission
Stability of antiretroviral regimens in patients with viral suppression
Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria
A population-based study of the incidence and molecular epidemiology of methicillin-resistant staphylococcus aureus disease in San Francisco, 2004-2005
Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms
High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets
The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients
Class-Sparing Regimens for Initial Treatment of HIV-1 Infection

Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants

Background: Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a potential malaria control strategy. There is concern about the impact that increasing in vivo resistance to SP has on the efficacy of IPTi, as well as about the potential contribution of IPTi to increases in resistance.

Methods/Intervention/Results: The authors compared the frequency of clinical episodes of malaria caused by P. falciparum parasites with mutations in dhfr and dhps among sick children who received SP or placebo in the context of a randomized, double-blind, placebo-controlled IPTi trial in Mozambique.

Half of the children who received placebo harbored quintuple-pure mutant parasites. Nevertheless, the protective efficacy of IPTi within the 35 days after the third dose was 70.8% (95% confidence interval [CI], 40.7%-85.6%). Between month 2 after the third IPTi dose and the end of the follow-up period, children receiving SP harbored more dhps codon 437 mixed infections (odds ratio [OR], 10.56 [95% CI, 1.30-86.14]) and fewer dhps double-pure mutant parasites (OR, 0.43 [95% CI, 0.22-0.84]) than did placebo recipients.

Authors' Conclusions: IPTi appears to be associated with some changes in the prevalence of genotypes involved in SP resistance. In the face of a high prevalence of quintuple-mutant parasites, SP exhibited a high level of efficacy in the prevention of new episodes of malaria in infants.

Early changes in T-cell activation predict antiretroviral success in salvage therapy of HIV infection.

Background: Because effective antiretroviral therapy (ART) reduces immune activation, the authors hypothesize that early changes in immune activation are associated with subsequent virologic response to therapy. The study was an observational cohort study of 34 adult HIV patients with virologic failure on their current antiretroviral regimen at an institutional HIV clinic.

Methods/Intervention/Results: the intervention was a change to salvage regimen selected by patient's physician. The main outcome measures were measures of immune activation at baseline and at 2, 4, 8, and 24 weeks after enrollment. Data were analyzed by proportional hazards (PH) models.

PH models showed that reductions between baseline and week 2 in expression of CD38 (P=0.02) or CD95 (P=0.02) on CD4+ T cells were associated with increased likelihood of achieving virologic suppression. Kaplan-Meier analysis demonstrated that patients who had reductions within the first 2 weeks of therapy in CD4+ T-cell expression of CD38 (P=0.003) or CD95 (P=0.08) were more likely to achieve viral suppression than those who did not.

Authors' Conclusions: Reduced CD4+ T-cell expression of CD38 and CD95 occurring within 2 weeks of salvage therapy is associated with subsequent viral suppression. Monitoring CD38 and CD95 may allow earlier assessment of the response to ART.

Differential extracellular and intracellular concentrations of zidovudine and lamivudine in semen and plasma of HIV-1-infected men

Background: The objectives of this study were to quantitate extracellular and intracellular zidovudine (ZDV) and lamivudine (3TC) concentrations in blood and semen of HIV-1-infected men. The study was designed as non-blind, single-center, open-label pharmacokinetic (PK) study in 14 subjects receiving ZDV plus 3TC.

Methods/Intervention/Results: Paired blood and semen samples were obtained during 1 intensive visit and 3 single time point visits over 2 weeks. Extracellular ZDV and 3TC concentrations were measured in blood plasma (BP) and seminal plasma (SP), and intracellular ZDV and 3TC triphosphate (TP) concentrations were measured in isolated mononuclear cells using validated methods. HIV-1 RNA was measured in blood and semen. PK parameters were estimated using noncompartmental analysis.

Median (interquartile range [IQR]) SP/BP area under the time-concentration curve over the 12-hour dosing interval (AUC0-12h) ratios for ZDV and 3TC were 2.28 (1.48 to 2.97) and 6.67 (4.10 to 9.14), respectively, whereas individual SP/BP concentration ratios ranged from 1.9 to 91.4. Intracellular median (IQR) SP/BP AUC0-12h ratios for ZDV-TP and 3TC-TP were 0.36 (0.30 to 0.37) and 1.0 (0.62 to 1.30), respectively, whereas individual SP/BP concentration ratios ranged from 0.11 to 2.9. HIV-1 RNA was undetectable in both compartments.

Authors' Conclusions: ZDV and 3TC SP exposures are 2- to 6-fold greater than BP exposures. Seminal ZDV-TP exposures are ~40% of those found in peripheral blood mononuclear cells (PBMCs), whereas 3TC-TP exposures are similar to PBMC exposures. PK variability makes individual SP/BP ratios a suboptimal surrogate for genital tract exposure.

Impact on hemoglobin of starting combination antiretroviral therapy with or without zidovudine in anemic HIV-infected patients

Background: The objective of this study was to evaluate, among anemic patients with HIV, the impact on hemoglobin (Hb) of initiating zidovudine (AZT)-containing and non-AZT-containing combination antiretroviral therapy (cART).

Methods/Intervention/Results: The authors used medical records data collected in 11 US cities from 1998 to 2004. Baseline anemia was described as mild (10

For 1620 patients initiating cART, more than half (54%) of patients had improvement of anemia. Time to improvement of anemia was longer for those initiating AZT-containing regimens and blacks and was shorter for those with moderate and severe anemia or CD4 counts <200 cells/µL.

Authors' Conclusions: Most anemic patients initiating cART (with or without AZT) had increases in Hb-especially those with more severe anemia or immunosuppression. Initiation of AZT-containing cART may be considered, even for patients with preexisting anemia; however, improvement of anemia may be delayed for black patients and for patients with mild disease.

The genotypic inhibitory quotient: a predictive factor of atazanavir response in HIV-1-infected treatment-experienced patients

Background: The objective of this study was to evaluate the predictive value of the genotypic inhibitory quotient (GIQ) on the atazanavir response in treatment-experienced HIV-1-infected patients.

Methods/Intervention/Results: Thirty-six patients receiving an atazanavir-containing regimen were enrolled in the study. Atazanavir plasma concentrations were measured at month (M) 1, and genotype was performed at baseline. Virologic response was defined as a viral load <400 copies/mL or a decrease =1 log10.

The median numbers (range) of previous regimens, baseline protease inhibitors, and atazanavir resistance mutations were 8 (0 to 20), 3 (0 to 15), and 1 (0 to 10), respectively. The atazanavir-GIQ was associated with virologic response at M6, with a median value (range) of 365 (50 to 1172) in responder patients compared with 126 (23 to 1126) in nonresponders (P=0.05). The cutoff value estimated for the atazanavir-GIQ was 183 (receiver operating characteristic curve test: 60% specificity, 74% sensitivity). Virologic response was achieved in 74% of patients with an atazanavir-GIQ >183 compared with only 26% of patients with an atazanavir-GIQ<183 (P=0.02). Neither the number of mutations nor the atazanavir trough concentration was predictive of the virologic response.

Authors' Conclusions: In pretreated patients, the atazanavir-GIQ might be useful to predict early virologic response and allow the determination of the target atazanavir trough concentration required to achieve virologic response and overcome drug resistance emergence in a given patient.

Antiretroviral therapy for HIV-infected tuberculosis patients saves lives but needs to be used more frequently in Thailand

Background: The impact of antiretroviral therapy (ART) on HIV-infected tuberculosis (TB) patients in public health programs in resource-limited settings is not well documented due to problems with statistical bias in observational studies.

Methods/Intervention/Results: The authors measured the impact of ART on survival of HIV-infected TB patients in Thailand using a propensity score analysis that adjusted for factors associated with receiving ART.

Of 626 HIV-infected TB patients started on ART during TB treatment, 68 (11%) died compared with 295/643 (46%) of patients not prescribed ART (relative risk 0.24, 95% confidence interval: 0.19 to 0.30); in patients with very low CD4 (<10), 12/56 (21%) patients receiving ART died compared with 35/43 (81%) patients not receiving ART (relative risk 0.26, 95% confidence interval: 0.16 to 0.44). Patients treated in the private sector and in rural areas were less commonly prescribed ART. After controlling for propensity to receive ART, the hazard ratio for death among patients treated with ART was 0.17 (95% confidence interval: 0.12 to 0.24).

Authors' Conclusions: Patients who received ART had one sixth the risk of death of those not receiving ART. The survival benefit persisted even for those with a very low CD4 count. Expanding use of ART in HIV-infected TB patients will require increasing ART use in the private sector and rural areas.

Adherence to antiretroviral therapy assessed by drug level monitoring and self-report in Cameroon

Background: The objectives of this study were to compare adherence to antiretroviral therapy using drug level monitoring and self-report and to explore the relation between these 2 methods and viral load measurements.

Methods/Intervention/Results: Sixty patients received a fixed-dose combination of nevirapine, stavudine, and lamivudine in a clinical study in Cameroon. Adherence was assessed every 6 months until month 36 by nevirapine minimal plasma concentration and self-report. Plasma HIV-1 viral load was determined at the same time. Analyses included 159 complete observations. The proportion of patients labeled as "adherent" was significantly lower using nevirapine monitoring (88.7%, 95% confidence interval [CI]: 82.7 to 93.2) than self-report (97.5%, CI: 93.7 to 99.3; P=0.002). Virologic failure was associated with the nevirapine concentration (adjusted odds ratio [aOR]=4.43; P=0.018) but not with the self-reported adherence (aOR=0.84; P=0.9). As compared with the virologic outcome, the sensitivity of nevirapine level monitoring for predicting inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4%, and the negative predictive value was 78.0%. For self-report, the respective values were 2.6%, 97.5%, 25.0%, and 75.5%.

Authors' Conclusions: Drug level monitoring provided a more reliable estimate of adherence than self-report. This method could be used in research settings. Operational research is required to define how to improve the accuracy of the self-report method because it is the most feasible method in clinical practice.

Citation: Kouanfack C, et al for the French National Agency for Research on AIDS 1274 Study Group. JAIDS 2008; 48(2): 216-9.

Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission

Background: The objective of this study was to determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission

Methods/Intervention/Results: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens.

Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P=0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR]=0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR=0.8, 95% CI: 0.3 to 1.8).

Authors' Conclusions: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.

Background: The 0bjective was to study the rate of treatment change due to toxicities in patients who achieved viral suppression within 6 months of starting antiretroviral therapy and who have never experienced virological failure.

Methods/Intervention/Results: Included patients attended the Royal Free Hospital in London, started antiretroviral therapy in 2000-2005, and achieved viral suppression within 6 months. Included follow-up (censored at virological failure) was spent on a regimen of lamivudine or emtricitabine, with a second nucleoside/nucleotide reverse transcriptase inhibitor, and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor.

In 912 person-years, there were 140 treatment changes due to toxicities (rate=15.4 per 100 person-years, confidence interval=12.8-17.9). In the multivariable analysis, factors associated with a higher rate of treatment change due to toxicities included increased age (for every 10 years increase: incidence rate ratio=1.28, confidence interval=1.04-1.57), being on stavudine compared with zidovudine (incidence rate ratio=2.04, confidence interval=1.28-3.26), and being on lopinavir compared with efavirenz (incidence rate ratio=1.55, confidence interval=1.04-2.31), whereas factors associated with a lower rate were being on tenofovir compared with zidovudine (incidence rate ratio=0.46, confidence interval=0.29-0.73), and being on atazanavir compared with efavirenz (incidence rate ratio=0.23, confidence interval=0.06-0.91).

Authors' Conclusions: In patients who have never experienced virological failure, the rate of treatment change due to toxicities is low, and certain regimens are associated with an even lower rate of change. If virological failure is avoided, some regimens are so far proving to be sufficiently stable to suggest that very long-term use is potentially feasible.

Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria

Background: Although malaria treatment aims primarily to eliminate the asexual blood stages that cause illness, reducing the carriage of gametocytes is critical for limiting malaria transmission and the spread of resistance.

Methods/Intervention/Results: Clinical and parasitological responses to the fixed-dose combination of sulfadoxine and pyrimethamine in patients with uncomplicated falciparum malaria were assessed biannually since implementation of this treatment policy in 1998 in Mpumalanga Province, South Africa.

Despite sustained cure rates of >90% (P=.14), the duration of gametocyte carriage increased from 3 to 22 weeks (per 1000 person-weeks) between 1998 and 2002 (P<.001). The dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance were the most important drivers of the increased gametocytemia, although these mutations were not associated with increased pretreatment asexual parasite density or slower asexual parasite clearance times. The geometric mean gametocyte duration and area under the gametocyte density time curve (per 1000 person-weeks) were 7.0 weeks and 60.8 gametocytes/µL per week, respectively, among patients with wild-type parasites, compared with 45.4 weeks (P=.016) and 1212 gametocytes/µL per week (P=.014), respectively, among those with parasites containing 1-5 dhfr/dhps mutations.

Authors' Conclusions: An increased duration and density of gametocyte carriage after sulfadoxine-pyrimethamine treatment was an early indicator of drug resistance. This increased gametocytemia among patients who have primary infections with drug-resistant Plasmodium falciparum fuels the spread of resistance even before treatment failure rates increase significantly.

A population-based study of the incidence and molecular epidemiology of methicillin-resistant staphylococcus aureus disease in San Francisco, 2004-2005

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections have become a major public health problem in both the community and hospitals. Few studies have characterized the incidence and clonal composition of disease-causing strains in an entire population. The objective was to perform a population-based survey of the clinical and molecular epidemiology of MRSA disease in San Francisco, California.

Methods/Intervention/Results: The authors prospectively collected 3985 MRSA isolates and associated clinical and demographic information over a 12-month period (2004-2005) at 9 San Francisco-area medical centers. A random sample of 801 isolates was selected for molecular analysis.

The annual incidence of community-onset MRSA disease among San Francisco residents was 316 cases per 100,000 population, compared with 31 cases per 100,000 population for hospital-onset disease. Persons who were aged 35-44 years, were men, and were black had the highest incidence of community-onset disease. The USA300 MRSA clone accounted for 234 cases of community-onset disease and 15 cases of hospital-onset disease per 100,000 population, constituting an estimated 78.5% and 43.4% of all cases of MRSA disease, respectively. Patients with community-onset USA300 MRSA versus non-USA300 MRSA disease were more likely to be male, be of younger age, and have skin and soft-tissue infections. USA300 strains were generally more susceptible to multiple antibiotics, although decreased susceptibility to tetracycline was observed in both community-onset (P=.008) and hospital-onset (P=.03) USA300 compared to non-USA300 strains.

Authors' Conclusions: The annual incidence of community-onset MRSA disease in San Francisco is substantial, surpassing that of hospital-onset disease. USA300 is the predominant clone in both the community and hospitals. The dissemination of USA300 from the community into the hospital setting has blurred its distinction as a community-associated pathogen.

Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms

Background: Telavancin is an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action.

Methods/Intervention/Results: The authors conducted 2 parallel, randomized, double-blind, active-control, phase 3 studies with a prespecified pooled analysis design. Patients aged 18 years who had complicated skin and skin-structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin (10 mg/kg intravenously every 24 h) or vancomycin (1 g intravenously every 12 h).

A total of 1867 patients were randomized and received 1 dose of study medication. In the clinically evaluable population, at 7-14 days after receipt of the last antibiotic dose, success was achieved in 88% and 87% of patients who received telavancin and vancomycin, respectively (95% confidence interval for the difference, -2.1 to 4.6). Methicillin-resistant Staphylococcus aureus was isolated at baseline from samples from 579 clinically evaluable patients. Among these patients with methicillin-resistant S. aureus infection, cure rates were 91% among patients who received telavancin and 86% among patients who received vancomycin (95% confidence interval for the difference, -1.1 to 9.3). Microbiologic eradication among patients infected with methicillin-resistant S. aureus was 90% in the telavancin treatment group and 85% in the vancomycin treatment group (95% confidence interval for the difference, -0.9 to 9.8). Therapy was discontinued because of adverse events in 8% and 6% of patients who received telavancin and vancomycin, respectively. Except for mild taste disturbance, nausea, vomiting, and serum creatinine concentration elevation in the telavancin treatment group and pruritus in the vancomycin treatment group, adverse events were similar between groups with regard to type and severity.

Authors' Conclusions: Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.

Citation: Stryjewski ME, et al on behalf of the Assessment of Telavancin in Complicated Skin and Skin-Structure Infections Study. Clin Infect Dis 2008; 46: 1683-93.

High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets

Background: Previous research in healthy volunteers has demonstrated that rifampicin and adjusted doses of lopinavir/ritonavir soft-gel capsules resulted in adequate exposure to lopinavir. The objective of this study was to study the combined use of rifampicin and the newly introduced lopinavir/ritonavir tablets.

Methods/Intervention/Results: A total of 40 healthy volunteers were planned to start with 600 mg rifampicin once daily from days 1-5. From days 6-15, volunteers were randomized to receive lopinavir/ritonavir tablets dosed as either 600/150 or 800/200 mg twice daily, both in addition to 600 mg rifampicin once daily. A 12 h pharmacokinetic curve was planned on day 15. Safety assessments were conducted regularly throughout the study period.

Eleven volunteers started as the first group in this study. No major complaints occurred during day 1-5 (rifampicin only). After addition of lopinavir/ritonavir, eight volunteers suffered from both nausea and vomiting, one from nausea only, and one from vomiting only. On day 7, increases in aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were reported in all volunteers and on day 8, the study was prematurely terminated. The AST/ALT levels continued to rise and peaked (grade 2, n=2; grade 3, n=1; grade 4, n=8) on days 9-10. All values returned to normal within 6 weeks.

Authors' Conclusions: The study showed a high incidence of adverse events when a higher than standard dose of the new lopinavir/ritonavir tablets was combined with rifampicin. In the future, this drug combination should not be given to healthy volunteers. Liver function should be carefully monitored when rifampicin and lopinavir/ritonavir are combined in patients.

The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients

Background: Entecavir, an antiviral with potent anti-hepatitis B virus activity, was recently shown to have anti-HIV activity in three patients and the ability to select for the lamivudine-resistant HIV polymerase mutation M184V in a patient with prior antiretroviral therapy. The objectives of this study were to further characterize entecavir's anti-HIV activity and identify risk factors for selection of the M184V.

Methods/Intervention/Results: This retrospective cohort study evaluated the virological characteristics of HIV and hepatitis B virus in 17 HIV-hepatitis B virus coinfected patients (10 antiretroviral therapy-naive and seven antiretroviral therapy-experienced) prior to and during entecavir monotherapy. Descriptive statistics were used to assess changes in HIV RNA and hepatitis B virus DNA. Variables associated with development of the M184V were determined by univariate analysis.

Of the 17 patients, 13 (76%) demonstrated a reduction in HIV RNA by at least 0.5 log10 copies/ml. Of the remaining four patients, two had the M184V detected prior to entecavir therapy and the other two had wild-type HIV. The median reduction in HIV RNA for the cohort was 1.2 log10 copies/ml, which was similar in antiretroviral therapy-naive and antiretroviral therapy-experienced patients. The M184V mutation emerged in six patients receiving entecavir, including three antiretroviral therapy-naive patients. No other HIV mutations were consistently detected. Risk factors for the emergence of the M184V mutation were a decline in hepatitis B virus DNA (P=0.04) and duration of entecavir use (P=0.05).

Authors' Conclusions: Entecavir monotherapy in HIV-hepatitis B virus coinfected patients, including antiretroviral therapy-naive patients, has significant anti-HIV activity and can result in the development of the M184V variant. Entecavir should not be used in such co-infected patients without concomitant antiretroviral therapy.

Background: The use of either efavirenz or lopinavir–ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir–ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.

Methods/Intervention/Results: An open-label study compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir–ritonavir plus two NRTIs (lopinavir–ritonavir group), and lopinavir–ritonavir plus efavirenz (NRTI-sparing group). The authors randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups.

At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir–ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir–ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir–ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups.

Authors' Conclusions: Virologic failure was less likely in the efavirenz group than in the lopinavir–ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance.

Citation: Riddler SA, et al for the AIDS Clinical Trials Group Study A5142 Team. N Engl J Med 2008; 358: 2095-106.