PubMed Health⌕ Search

Biomedical subjects

Pablo Tebas

Publications and source records attributed to Pablo Tebas.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence, risk factors, and outcomes for occult hepatitis B virus infection among HIV-infected patients.

BACKGROUND: Occult hepatitis B virus (HBV) is defined by the presence of HBV DNA in individuals with HBV core antibodies (anti-HBc) but without HBV surface antigen (HBsAg). The prevalence of occult HBV in HIV-infected patients remains controversial, and the risk factors and clinical significance are unknown. OBJECTIVES: To determine the prevalence, risk factors, and clinical significance of occult HBV among HIV-infected patients. Hypothesized risk factors include chronic hepatitis C virus (HCV), CD4 count < 200 cells/mm, HIV RNA level >1000 copies/mL, and lack of use of anti-HBV antiretrovirals. METHODS: We examined randomly selected HBsAg/anti-HBc HIV-infected patients in the Penn Center for AIDS Research Adult/Adolescent Database and Specimen Repository. HBV DNA was qualitatively detected using a transcription-mediated amplification assay. Risk factors and transaminases were ascertained at the time sera were collected. RESULTS: A total of 699 HBsAg/anti-HBc HIV-infected patients were identified. Of 179 randomly selected subjects, 17 (10%; 95% confidence interval [CI]: 5% to 14%) had occult HBV. Differences in the prevalence of HBV surface antibody (anti-HBs) between those with (7 [41%]) and without (94 [58%]) occult HBV were not statistically significant (P = 0.3). An HIV RNA level >1000 copies/mL (adjusted odds ratio [OR] = 4.88, 95% CI: 1.01 to 30.26) and the absence of chronic HCV (adjusted OR = 0.26, 95% CI: 0.05 to 0.95) were associated with occult HBV. Occult HBV did not increase the risk of transaminitis (adjusted OR = 0.42, 95% CI: 0.12 to 1.45). CONCLUSIONS: Occult HBV occurred in a sizable proportion of HIV-infected patients and was associated with detectable HIV and the absence of chronic HCV. It did not increase the risk of transaminitis. The presence of anti-HBs does not rule out occult HBV. Future studies should examine the long-term clinical implications of occult HBV in HIV-infected patients.

Adult↗
PubMed2007

Cardiovascular risks of antiretroviral therapies.

The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.

Anti-Retroviral Agents↗
PubMed2006

Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138.

BACKGROUND: Although the determinants of immune deficiency and immune restoration in chronic human immunodeficiency virus (HIV)-1 infection are not well understood, immune activation has been proposed as being central to the pathogenesis of HIV. METHODS: A randomized, controlled trial of cyclosporin A treatment for 2 weeks was performed in persons with chronic HIV-1 infection who were beginning a standardized antiretroviral therapy (ART) regimen. RESULTS: Treatment with cyclosporin A provided only a marginal and transient enhancement in circulating T cell restoration that was largely restricted to cells expressing the CCR7 chemokine receptor and that did not persist beyond 2 weeks. CONCLUSIONS: Cyclosporin A coadministered for 2 weeks with ART provided no sustained immunologic benefit to persons with chronic HIV-1 infection. If immune activation drives progressive immune deficiency in chronic HIV-1 infection, these activation pathways may not be sensitive to cyclosporin.

Adult↗
PubMed2006

Mixed patterns of changes in central and peripheral fat following initiation of antiretroviral therapy in a randomized trial.

INTRODUCTION: Although peripheral fat loss is a consistent feature of HIV-associated lipodystrophy, less is known about whether changes in central and peripheral fat occur in tandem or independently over time. We examined intraindividual changes in dual-energy x-ray absorptiometry (DEXA) and anthropometry data over 64 weeks after initiation of antiretroviral therapy (ART). METHODS: In ACTG 384, ART-naive subjects were randomized to receive didanosine and stavudine or zidovudine and lamivudine plus efavirenz, nelfinavir, or both. In the metabolic substudy A5005S (N= 329), waist, hip, thigh, and arm circumferences were measured in triplicate. DEXA scanning was performed in 157 subjects. RESULTS: Individual changes in limb and trunk fat at week 64 correlated positively (R =.72, P <.001). Most subjects had directionally concordant changes in limb and trunk fat (36% gained and 32% lost in both regions). In 26%, trunk fat increased while limb fat decreased, whereas the reverse occurred in only 6% (P <.001). Changes in waist and hip circumferences also correlated positively (R =.62, P <.001). The proportion of subjects with waist/hip ratio more than .95 (men) or .90 (women) was 34% at baseline and 47% at week 64 (P =.003). In those who developed increased waist/hip ratio, 76% had increased waist circumference. CONCLUSIONS: Individual results obtained by both anthropometry and DEXA show diverse patterns of fat gain and loss over 64 weeks after initiation of ART, but changes tended to occur in the same direction. Increased waist/hip ratio was predominantly associated with increased waist circumference. There was no evidence that central fat accumulation and peripheral fat loss are linked in most subjects.

Absorptiometry, Photon↗
PubMed2006

Real-time nucleic acid sequence-based amplification assay to quantify changes in mitochondrial DNA concentrations in cell cultures and blood cells from HIV-infected patients receiving antiviral therapy.

BACKGROUND: To study the clinical relevance of changes in mitochondrial DNA (mtDNA) in peripheral blood mononuclear cells (PBMCs) attributable to HIV infection and/or combination antiretroviral therapy (cART), a high-throughput molecular assay to quantify mtDNA is required. METHODS: We developed a quantitative real-time duplex nucleic acid sequence-based amplification assay in which both mtDNA and nuclear DNA are simultaneously amplified in 1 tube. The assay could accurately quantify mtDNA in a range of 15-1500 copies of mtDNA per 2 genomic copies with an intrarun variation of 11% and an interrun variation of 16%. We compared this real-time assay with the lactate/pyruvate ratios in fibroblasts incubated with glucose and exposed to zalcitabine. Additionally, we studied the effects of platelet contamination and the in vivo effects of cART on mtDNA in PBMCs from a small group of patients. RESULTS: Decreases in mtDNA preceded the increase in lactate/pyruvate ratios and vice versa when zalcitabine was eliminated from the culture. Platelets affected the mtDNA in PBMCs if >5 platelets per PBMC were present. Within 12 weeks, mtDNA increased and remained increased in PBMCs from patients on continuous treatment with zidovudine/lamivudine/indinavir therapy (P = 0.03), but increased if patients were switched to stavudine/didanosine therapy (P = 0.008). CONCLUSION: After drug exposure, the mtDNA assay can detect changes in mtDNA concentrations in cell lines and PBMCs, when properly controlled for platelet effects, earlier than traditional assays.

Anti-HIV Agents↗
PubMed2006

Management of potential neurocysticercosis in patients with HIV infection.

In patients with human immunodeficiency virus, the diagnosis of neurocysticercosis can be complex, and the current diagnostic criteria may not apply. We report 3 cases and suggest including the CD4+ T lymphocyte count as an important factor in the proper diagnosis and treatment of patients with human immunodeficiency virus and potential neurocysticercosis.

Adult↗
PubMed2006

A pilot study evaluating time to CD4 T-cell count <350 cells/mm(3) after treatment interruption following antiretroviral therapy +/- interleukin 2: results of ACTG A5102.

BACKGROUND: Although an intermittent antiviral treatment (ART) strategy may limit long-term toxicity and cost, there is concern about the risk for virologic failure, selection of drug resistance mutations, and disease progression. By boosting CD4 T-cell counts, interleukin 2 (IL-2) could safely prolong the duration of treatment interruption (TI) in a CD4-driven strategy. METHODS: The AIDS Clinical Trials Group (ACTG) study A5102 evaluated 3 cycles of IL-2 before TI, on clinical and immunologic outcomes, using a CD4 T-cell count of <350 cells/mm as the threshold for restarting ART. Forty-seven HIV-infected subjects on potent ART with CD4 T-cell counts of > or =500 cells/mm or more and HIV RNA levels of less than 200 copies/mL were randomized to arm A (ART + three 5-day cycles of IL-2 at 4.5 million U, Sc, BID every 8 weeks, n = 23) or arm B (ART alone, n = 24) for 18 weeks (step 1). At the end of step 1, subjects with a CD4 T-cell count of > or =500 cells/mm or more stopped ART until a CD4 count of <350 cells/mm (step 2). CD4 T-cell count, time to return of viremia, and the emergence of drug resistance mutations after TI were compared between study arms. RESULTS: IL-2 recipients maintained higher CD4 counts during TI for 48 weeks with a waning of the CD4 effect by 72 weeks. A sustained CD4 T-cell count of more than 350 cells/mm and more durable TI were associated with a higher nadir CD4 T-cell count before ART and higher naive CD4 T-cell count at entry. After TI, a higher viral set point and drug resistance mutations at virologic rebound were associated with a shorter time to CD4 T-cell count of less than 350 cell/mm. There were no differences in the magnitude of virologic rebound (at week 8 of step 2, median log10 HIV RNA level was 4.23 for arm A and 4.21 for arm B) or the steady-state HIV-1 RNA level after week 8. CONCLUSIONS: IL-2 before TI did not prolong time to CD4 of less than 350 cells/mm. A TI strategy utilizing a CD4 T-cell threshold of less than 350 cells/mm for restarting ART appears generally safe with most subjects in both arms remaining off ART for more than 1 year. Implications of our results for TI strategies include the potential advantage of starting ART at higher CD4 T-cell levels while avoiding any drug resistance and evaluating immunomodulators or drugs to reduce T-cell activation and HIV-1 RNA rebound during the TI.

Adult↗
PubMed2006

Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy.

BACKGROUND: Protease inhibitors (PIs) are associated with hypertriglyceridemia and atherogenic dyslipidemia. Identifying HIV-1-infected individuals who are at increased risk of PI-related dyslipidemia will facilitate therapeutic choices that maintain viral suppression while reducing risk of atherosclerotic diseases. Apolipoprotein C-III (apoC-III) gene variants, which vary by race/ethnicity, have been associated with a lipid profile that resembles PI-induced dyslipidemia. However, the association of race/ethnicity, or candidate gene effects across race/ethnicity, with plasma lipid levels in HIV-1-infected individuals, has not been reported. METHODS AND FINDINGS: A cross-sectional analysis of race/ethnicity, apoC-III/apoA-I genotypes, and PI exposure on plasma lipids was performed in AIDS Clinical Trial Group studies (n = 626). Race/ethnicity was a highly significant predictor of plasma lipids in fully adjusted models. Furthermore, in stratified analyses, the effect of PI exposure appeared to differ across race/ethnicity. Black/non-Hispanic, compared with White/non-Hispanics and Hispanics, had lower plasma triglyceride (TG) levels overall, but the greatest increase in TG levels when exposed to PIs. In Hispanics, current PI antiretroviral therapy (ART) exposure was associated with a significantly smaller increase in TGs among patients with variant alleles at apoC-III-482, -455, and Intron 1, or at a composite apoC-III genotype, compared with patients with the wild-type genotypes. CONCLUSIONS: In the first pharmacogenetic study of its kind in HIV-1 disease, we found race/ethnic-specific differences in plasma lipid levels on ART, as well as differences in the influence of the apoC-III gene on the development of PI-related hypertriglyceridemia. Given the multi-ethnic distribution of HIV-1 infection, our findings underscore the need for future studies of metabolic and cardiovascular complications of ART that specifically account for racial/ethnic heterogeneity, particularly when assessing candidate gene effects.

Black or African American↗
PubMed2005

Bone disease and HIV infection.

The high prevalence of bone demineralization among human immunodeficiency virus (HIV)-infected patients in the current therapeutic era has been described in multiple studies, sounding the alarm that we may expect an epidemic of fragility fractures in the future. However, despite noting high overall prevalences of osteopenia and osteoporosis, recent longitudinal studies that we review here have generally not observed accelerated bone loss during antiretroviral therapy beyond the initial period after treatment initiation. We discuss the continued progress toward understanding the mechanisms of HIV-associated bone loss, particularly the effects of HIV infection, antiretroviral therapy, and host immune factors on bone turnover. We summarize results of clinical trials published in the past year that studied the safety and efficacy of treatment of bone loss in HIV-infected patients and provide provisional opinions about who should be considered for bone disease screening and treatment.

Adult↗
PubMed2005

Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides.

OBJECTIVE: To determine if particular components of antiretroviral drug regimens are associated with greater insulin resistance, dyslipidemia, and peripheral lipoatrophy. METHODS: Metabolic and body composition variables were measured prospectively over 64 weeks in 334 antiretroviral-naive, HIV-infected subjects who were randomized to receive nelfinavir, efavirenz, or both, combined with zidovudine/lamivudine or didanosine/stavudine in a factorial design, multicenter trial. Subjects assigned to efavirenz (n = 110) were compared with those assigned to nelfinavir (n = 99); subjects assigned to zidovudine/lamivudine (n = 154) were compared with those assigned to didanosine/stavudine (n = 180). A subset of 157 subjects had serial dual-energy X-ray absorptiometry (DEXA) scans. RESULTS: Lipid measures increased in all groups. Greater increases in high density lipoprotein (HDL) cholesterol occurred with efavirenz than with nelfinavir. Greater increases in total cholesterol, non-HDL cholesterol and HDL cholesterol occurred with stavudine and didanosine than with zidovudine/lamivudine. There were no differences in insulin resistance in the comparisons. After initial increases in the first 16 weeks, median limb fat decreased. Greater changes in percentage changes in limb fat occurred with didanosine/stavudine (-16.8%) than with zidovudine/lamivudine (+4.0%; P < 0.001 for overall change from baseline) and with nelfinavir (-13.1%) compared with efavirenz (+1.8%; P = 0.003). CONCLUSIONS: Over 64 weeks, all regimens were associated with increases in lipids but insulin resistance did not differ between groups. Regimens containing didanosine/stavudine and regimens containing nelfinavir were associated with greater loss of limb fat.

Absorptiometry, Photon↗
PubMed2005

Distinct mechanisms of T cell reconstitution can be identified by estimating thymic volume in adult HIV-1 disease.

BACKGROUND: We have attempted to identify factors associated with T cell reconstitution in response to highly active antiretroviral therapy. METHODS: In a prospective, multicenter cohort study, we compared clinical, immune, and viral responses to an initial antiretroviral regimen in older (>or=45 years old) versus younger (18-30 years old) human immunodeficiency virus type 1-infected subjects. Multivariable linear-regression models identified independent factors associated with changes in T cell counts. RESULTS: Older subjects had smaller increases in naive T cells but greater T cell receptor-excision circle DNA content after 48 weeks, despite similar virologic responses and comparable reductions in immune activation. Changes in T cell counts were associated with plasma interleukin (IL)-7 levels in subjects with low thymic scores, whereas first-phase T cell increases (perhaps mediated by redistribution to the circulation of tissue-associated lymphocytes) were associated with reductions in immune activation in subjects with high thymic scores. Reductions in immune activation were associated with reductions in spontaneous lymphocyte apoptosis. CONCLUSIONS: Distinct processes may underlie T cell restoration, according to estimated thymic volumes. IL-7-mediated peripheral expansion may drive T cell restoration in persons with low thymic volume, whereas therapy-associated reversal of immune reactivation may drive T cell losses and their restoration in persons with larger thymic volume.

Adolescent↗
PubMed2005

A tale of 2 epidemics: the intersection between obesity and HIV infection in Philadelphia.

BACKGROUND: Obesity and HIV infection are ongoing epidemics in the United States. Obesity predisposes to diabetes and cardiovascular disease, which are complications also associated with HIV and/or its treatment. OBJECTIVE: To determine the prevalence and risk factors for overweight and obesity in HIV-infected individuals. DESIGN AND SETTING: Retrospective cross-sectional study in which 1689 patients enrolled in the University of Pennsylvania Center for AIDS Research Adult/Adolescent Database at 1 university hospital clinic, 2 affiliated practices, and 1 Veterans Administration clinic in Philadelphia had demographic, social, and medical data collected prospectively since 1999. PARTICIPANTS: Body mass index (BMI) data were available for 1669 HIV-infected subjects: 78% were men, and 60% were African American. The median CD4 count was 381 cells/microL, 47% of subjects had a viral load <400 copies/mL, and 9% of subjects were treatment naive. MAIN OUTCOME MEASURES: The prevalence and risk factors for overweight (BMI: 25-29.9 kg/m) and obesity (BMI>or=30 kg/m) in HIV-infected subjects. RESULTS: Obesity and overweight were more prevalent than wasting (14%, 31%, and 9%, respectively; P<0.0005), but they were not more common than in the general population. Although women and men were equally overweight (30% vs. 31%), women were more obese than men (28% vs. 11%; P<0.001). Among women, African American race (odds ratio [OR]=1.8, 95% confidence interval [CI]: 1.1-2.9) and a CD4 count>or=200 cells/microL (OR=2.8, 95% CI: 1.6-4.9) were associated with overweight and obesity. Among men, only a CD4 count>or=200 cells/microL (OR=1.6, 95% CI: 1.04-2.4) was associated with increased BMI. In men and women, smoking was associated with decreased obesity and overweight (OR=0.59, 95% CI: 0.47-0.74 and OR=0.65, 95% CI: 0.43-0.98, respectively). Age, income, employment, education, past or current intravenous drugs, being on HIV treatment, and viral load were not associated with obesity in the multivariate model. There was a positive correlation between BMI and total cholesterol, triglycerides, and glucose. CONCLUSION: Obesity is more common than wasting in this therapeutic era. Women, particularly those of African American race, are at high risk. Obesity might add to metabolic abnormalities associated with HIV or its treatment and contribute to morbidity, as patients with HIV live longer.

Adolescent↗
PubMed2005

Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection.

BACKGROUND: Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48-week prospective, randomized, open-label study to evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone mineral density (BMD) in patients with HIV infection. METHODS: Thirty-one HIV-infected subjects with lumbar spine BMD t-scores less than -1.0 on antiretroviral therapy for a minimum of 6 months were randomized to receive (n = 15) or not to receive (n = 16) 70 mg of alendronate weekly for 48 weeks. All subjects received calcium (1000 mg daily as calcium carbonate) and vitamin D supplementation (400 IU daily). The study was powered to detect 3% changes in BMD in the lumbar spine within arms at 48 weeks. RESULTS: Thirty-one patients were enrolled; most were male, with an average length of HIV infection of 8 years. Eighty-four percent had an HIV RNA load below 400 copies/mL, with a current median CD4+ T-cell count of 561 cells/mm3 (median nadir CD4 cell count of 167 cells/mm). At baseline, the median t-score in the lumbar spine was -1.52 and the median t-score in the hip was -1.02. Alendronate in combination with vitamin D and calcium increased lumbar spine BMD by 5.2% (95% confidence interval [CI]: 1.3-6.4) at 48 weeks compared with an increase of 1.3% (95% CI: -2.4 to 4.0) in subjects receiving vitamin D and calcium alone. One subject discontinued treatment in each arm. There were no serious adverse events. CONCLUSIONS: Alendronate, vitamin D, and calcium are safe and potentially useful in the treatment of osteopenia/osteoporosis associated with HIV infection.

Absorptiometry, Photon↗
PubMed2005

Plasmid vaccination of stable HIV-positive subjects on antiviral treatment results in enhanced CD8 T-cell immunity and increased control of viral "blips".

Antiviral therapy prolongs suppression of viral replication and allows for significant immune reconstitution but has not been effective in eradicating reservoirs of virus, which produce resurgent viremia when highly active antiretroviral therapy (HAART) is discontinued. Immune-based therapy may provide an additional antiviral effect. We vaccinated stable HIV-positive patients on HAART with an HIV plasmid vaccine to determine safety, immunogenicity, and therapeutic potential. Volunteers received a combination of two HIV DNA plasmid constructs, which drive expression of env/rev and gag/pol genes. The vaccine was well tolerated with no toxicity. CD4 and CD8 lymphocyte counts did not change significantly among volunteers. CD8 MHC class I-restricted responses to HIV antigens were assayed. Eight of 13 vaccinees responded after vaccination with detectable ELISpot result. Importantly, we observed a difference in viral detection events in vaccinated compared to control patients. Three out of the five placebo recipients had "viral blips" (transient elevations of HIV RNA) during follow-up (10/49 assays) while these were only present in one of 13 vaccinees on one occasion (1/130 assays; p<0.04). The decrease in the frequency of transient viremia and failure suggests that DNA immunization with CD8-generating vaccines in HAART-controlled HIV-positive subjects may have therapeutic potential.

AIDS Vaccines↗
PubMed2005

Treating morphologic and metabolic complications in HIV-infected patients on antiretroviral therapy. A consensus statement of an advisory committee of the International Association of Physicians in AIDS Care.

OBJECTIVE: Clinicians are increasingly challenged by presentation of morphologic and metabolic complications in HIV-infected patients. These complications are associated with HIV infection and/or combination antiretroviral therapy. This Consensus Statement is intended to offer guidance to clinicians actively involved in HIV/AIDS care. PARTICIPANTS: Seven clinicians with expertise in HIV medicine were invited by the International Association of Physicians in AIDS Care (IAPAC) to serve on an ad hoc Advisory Committee. CONSENSUS PROCESS: IAPAC convened the Advisory Committee to develop a draft Consensus Statement. Each clinician was tasked with drafting a specific section of the Consensus Statement corresponding with his or her expertise around a morphologic and/or metabolic complication. Scientific and clinical research, and other data in published literature and abstracts from scientific conferences were considered by strength of evidence. This document represents the consensus agreement of the Advisory Committee.

Anti-HIV Agents↗
PubMed2004

Niacin in HIV-infected individuals with hyperlipidemia receiving potent antiretroviral therapy.

BACKGROUND: Extended release (ER)-niacin therapy, which has been associated with reduced glucose tolerance in human immunodeficiency virus (HIV)-seronegative individuals, has not been evaluated in the HIV-infected population. METHODS: This open, prospective trial evaluated the safety and efficacy of ER-niacin therapy for antiretroviral therapy-associated dyslipidemia. Fourteen individuals received ER-niacin at maximum doses of 2000 mg per day for 14 weeks. RESULTS: Significant reductions in serum levels of triglycerides (P=.02), total cholesterol (P=.005), and non-HDL cholesterol (P=.04) were seen after ER-niacin therapy. Seven of 11 subjects were glucose intolerant after ER-niacin therapy; for 3 of these subjects, this was a new finding. Beta-cell sensitivity to basal glucose levels increased significantly without concomitant increase in overall glucose disposition indices. The values for the homeostasis model of insulin resistance index increased significantly (P=.005). CONCLUSION: ER-niacin's role in the treatment of antiretroviral therapy-associated dyslipidemia requires further evaluation, but the results of this pilot study indicate that it is safe and tolerated and provides a valuable treatment option.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine.

BACKGROUND: Cross resistance is common among the non-nucleoside reverse transcriptase inhibitors (NNRTIs). G190A appears in 5-15% of the patients treated with nevirapine or efavirenz who develop clinical resistance. OBJECTIVES: In this study we investigated the effect of G190A and other NNRTI substitutions on the phenotypic susceptibility to this class of drugs. STUDY DESIGN: We identified 15 individuals, who after treatment with NNRTIs (nevirapine or efavirenz; median exposure of 20 months), developed isolated G190A, G190A in combination with K103N, or K103N alone. Phenotypic and genotypic analyses of stored plasma specimens were performed before and after the mutations occurred to assess NNRTI susceptibility. RESULTS: All isolates that developed only G190A substitution became less susceptible to nevirapine (median: 125-fold) and efavirenz (median: 10-fold) but were 2.5-fold more sensitive to delavirdine (Wilcoxon P = 0.06). In the group with only K103N substitution, acquisition of resistance to all NNRTIs was observed. In the group with the double substitutions, G190A and K103N, delavirdine susceptibility decreased 13-fold, while resistance to nevirapine and efavirenz decreased by 239- and 154-folds, respectively (Kruskal-Wallis H P = 0.009). CONCLUSIONS: The data suggest that the presence of a G190A substitution attenuates the phenotypic resistance associated with a K103N substitution, although resistance is still present. The in vivo significance of the increased phenotypic susceptibility to delavirdine is not known but could be evaluated in a clinical trial.

Anti-HIV Agents↗