A Phase 1 study of a recombinant viruslike particle vaccine against human papillomavirus type 11 in healthy adult volunteers.

Viruslike particles (VLPs) produced from the L1 protein of several papillomaviruses have induced protection from infection after live challenge in animal models. In the present study, the safety and immunogenicity of a human papillomavirus (HPV)--11 L1 VLP candidate vaccine were measured in a phase 1, dose-finding trial in humans. The vaccine was well tolerated and induced high levels of both binding and neutralizing antibodies. Marked increases in lymphoproliferation to HPV--11 L1 antigens were noted after the second vaccination. In addition, lymphoproliferation was induced after vaccination in peripheral blood mononuclear cells (PBMC) stimulated with heterologous L1 VLP antigens of HPV types 6 and 16. Statistically significant increases in HPV antigen--specific interferon--gamma and interleukin-5 production were measured from PBMC culture supernatants. This candidate HPV VLP vaccine induced robust B and T cell responses, and T cell helper epitopes appear to be conserved across HPV types.

Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture.

Three mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (V106A, V179D, and Y181C), which occur in clinical isolates and confer resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), were analyzed for RNA- and DNA-dependent DNA polymerization and RNase H cleavage. All mutants demonstrated processivities of polymerization that were indistinguishable from wild-type enzyme under conditions in which deoxynucleoside triphosphates were not limiting. The V106A reverse transcriptase demonstrated a three- to fourfold slowing of both DNA 3'-end-directed and RNA 5'-end-directed RNase H cleavage relative to both wild-type and V179D enzymes, similar to what was observed for P236L in a previously published study (P. Gerondelis et al., J. Virol. 73:5803-5813, 1999). In contrast, the Y181C reverse transcriptase demonstrated a selective acceleration of the secondary RNase H cleavage step during both modes of RNase H cleavage. The relative replication fitness of these mutants in H9 cells was assessed in parallel infections as well as in growth competition experiments. Of the NNRTI-resistant mutants, V179D was more fit than Y181C, and both of these mutants were more fit than V106A, which demonstrated the greatest reduction in RNase H cleavage. These findings, in combination with results from previous work, suggest that abnormalities in RNase H cleavage are a common characteristic of HIV-1 mutants resistant to NNRTIs and that combined reductions in the rates of DNA 3'-end- and RNA 5'-end-directed cleavages are associated with significant reductions in the replication fitness of HIV-1.

Analysis of env sequence evolution in human immunodeficiency virus-infected patients receiving therapy with nonnucleoside reverse-transcriptase inhibitors.

Nonnucleoside reverse-transcriptase inhibitors (NNRTIs) can rapidly select for drug-resistant human immunodeficiency virus type 1 (HIV-1) variants, although their effect on HIV-1 quasi-species diversity is unknown. To determine if changes in env gene diversification occur with NNRTI therapy, we used the heteroduplex tracking assay (HTA) to study HIV-1 env sequence diversity in 2 groups of patients: those who were on no therapy or were on chronic antiretroviral therapy and those who had just initiated NNRTIs. Forty-nine paired samples from 46 patients were analyzed. Fourteen of 32 paired samples from the NNRTI group and 9 of 17 paired samples from the control group had HTA changes (P>.10). There was no correlation between HTA change and sampling time interval, baseline virus load, change in virus load, or development of NNRTI resistance. Thus, we found no significant correlation of NNRTI therapy with changes in env HTA patterns, suggesting that these treatments had little short-term impact on HIV-1 quasi-species diversity.

Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. The ACTG 187 and 199 study teams.

RATIONALE: To determine the dosage requirements and pharmacokinetics of atevirdine, a non-nucleoside reverse transcriptase inhibitor and its N-dealkylated metabolite (N-ATV) during phase I studies in patients receiving atevirdine alone or in combination with zidovudine. DESIGN: Two open label, phase I studies conducted by the adult AIDS Clinical Trials Group (ACTG) in which atevirdine was administered every 8 h with weekly dosage adjustments to attain targeted trough plasma atevirdine concentrations. SETTING: Five Adult AIDS Clinical Trials Units. PATIENTS: Fifty patients (ACTG 199; n = 20 and ACTG 187; n = 30) with HIV-1 infection and < or =500 CD4+ lymphocytes/mm3. INTERVENTION: ACTG 199; 12 weeks of therapy with atevirdine (dose-adjusted to achieve plasma trough atevirdine concentrations of 5-10 microM) and zidovudine (200 mg every 8 h). ACTG 187: 12 weeks of atevirdine monotherapy with atevirdine doses adjusted to achieve escalating, targeted trough plasma concentration ranges (5-13, 14-22, and 23-31 microM). MEASUREMENTS: ACTG 199: atevirdine, N-ATV and zidovudine trough determinations weekly (all patients) and intensive pharmacokinetics (selected patients) prior to and at 6 and 12 weeks during combination therapy. ACTG 187: atevirdine and N-ATV trough concentrations over a 12 week period. Intensive pharmacokinetic studies were conducted prior to and at 4 and/or 8 weeks during atevirdine monotherapy in female patients. RESULTS: Atevirdine plasma concentrations demonstrated considerable interpatient variability which was minimized by the adjustment of maintenance doses (range: 600-3900 mg/day) to achieve the desired trough concentrations. In ACTG 187, the mean number of weeks to attain the target value, and the percentage of patients who attained the target, was group I (5-11 microM): 2.7+/-2.4 weeks (92%); group II (12-21 microM): 2.6+/-1.8 (64%); and group III (22-31 microM): 7.0+/-5.6 weeks (27%). In ACTG 199 it was 3.2+/-5.2 weeks (95%) to achieve a 5-10 microM trough. Atevirdine demonstrated a mono- or bi-exponential decline among most of the patients studied after the first dose. During multiple-dosing a number of patterns of atevirdine disposition were observed including; rapid absorption with Cmax at 0.5-1 h, delayed absorption with Cmax at 3-4 h; minimal Cmax to Cmin fluctuation and Cmax to Cmin ratios of > 4. N-ATV (an inactive metabolite) patterns were characterized on day one by rapid appearance of the metabolite which peaked at 2-3 h after the dose and declined in a mono- or bi-exponential manner. At steady-state N-ATV patterns demonstrated minimal Cmax to Cmin fluctuations with some of the patients having more stable plasma N-ATV concentrations, while others had greater fluctuations week to week. CONCLUSIONS: Considerable interpatient variability was noted in the pharmacokinetics of atevirdine. The variation in drug disposition was reflected in the range of daily doses required to attain the targeted trough concentrations. Atevirdine metabolism did not appear to reach saturation during chronic dosing in many of our patients, as reflected by the pattern of N-ATV/ATV ratios in plasma and saturation was not an explanation for the variation in dosing requirements. No apparent differences were noted between males and females, and atevirdine did not appear to influence zidovudine disposition.

Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team.

The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had < or =100 CD4 T cells/microL in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4. 7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P=.005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P=. 0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P=.36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P<.001).

Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260).

The development of human immunodeficiency virus type 1 resistance to delavirdine (DLV) was studied in subjects receiving DLV monotherapy. Phenotypic resistance developed in 28 of 30 subjects within 8 weeks. K103N and Y181C, which confer nonnucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance, were the predominant reverse transcriptase mutations. P236L, which confers DLV resistance but hypersensitivity to other NNRTIs, developed in <10% of isolates.

The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities.

The nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) delavirdine (DLV) selects in vitro for the human immunodeficiency virus type 1 (HIV-1) RT mutation P236L, which confers high-level resistance to DLV but not other NNRTIs. Unexpectedly, P236L has developed infrequently in HIV-1 isolates obtained from patients receiving DLV; K103N is the predominant resistance mutation observed in that setting. We characterized the replication fitness of viruses derived from pNL4-3 containing P236L or K103N in both H9 and primary human peripheral blood mononuclear cell cultures infected in parallel with the two mutants. In the absence of DLV, p24 production by wild-type virus occurred more rapidly and to higher levels than with either mutant; P236L consistently demonstrated a two- to threefold decrease in p24 relative to K103N. At low levels of DLV, growth of wild-type virus was severely inhibited, and K103N replicated two- to threefold more efficiently than P236L. At high concentrations of DLV, P236L replication and K103N replication were both inhibited. Recombinant RTs containing K103N or P236L were analyzed for DNA polymerization on heteropolymeric RNA templates and RNase H degradation of RNA-DNA hybrids. Neither mutant demonstrated defects in polymerization. K103N demonstrated normal RNA 5'-end-directed RNase H cleavage and slowed DNA 3'-end-directed RNase H cleavage compared to wild-type RT. P236L demonstrated slowing of both DNA 3'-end- and RNA 5'-end-directed RNase H cleavage, consistent with its reduced replication efficiency relative to K103N. These data suggest that NNRTI resistance mutations can lead to reductions in the efficiency of RNase H cleavage, which may contribute to a reduction in the replication fitness of HIV-1.

Association of human papillomavirus infection and disease with magnitude of human immunodeficiency virus type 1 (HIV-1) RNA plasma level among women with HIV-1 infection.

Ninety-three women with human immunodeficiency virus type 1 (HIV-1) infection were enrolled in a cross-sectional study to evaluate the relationship between plasma HIV-1 RNA levels and coincident cervical infection and disease caused by human papillomaviruses (HPVs). HIV-1 RNA plasma levels of >10,000 copies/mL were highly associated with the presence in cervical specimens of HPV DNA of oncogenic (high risk) virus genotypes (P=.006; relative risk, 2.57). In addition, similar HIV-1 RNA plasma levels were associated with abnormal Pap smears (P=.01; relative risk, 2.11). In this study, 81% of women with high-risk HPV cervical infection had abnormal Pap smears. Measurement of HIV-1 RNA plasma levels may help to identify a subgroup of HIV-1-infected women at increased risk for cervical HPV infection and disease.

Highly active antiretroviral therapy results in a decrease in CD8+ T cell activation and preferential reconstitution of the peripheral CD4+ T cell population with memory rather than naive cells.

OBJECTIVE: Highly active antiretroviral therapy (HAART) can produce marked increases in peripheral blood CD4+ T cells and decreases in HIV plasma RNA copy numbers. However, it is not clear whether these absolute changes will be accompanied by a recovery in the known naive CD4+ T cell depletion or a decrease in the marked CD8+ T cell activation. DESIGN: Twenty-nine patients were enrolled in studies of either nucleoside therapy alone or nucleoside therapy combined with a protease inhibitor (zidovudine + lamivudine + indinavir). One hundred and ninety-one examinations were carried out at three baseline time points and during 40 weeks of follow-up to evaluate the effect of HAART on CD4+ memory/naive phenotype and CD8+ T cell activation. METHODS: CD4+ and CD8+ T cell number, CD62L/CD45RA expression on CD4+ T cells and CD38 expression on CD8+ T cells were measured by three-color flow cytometry. RESULTS: Most protease inhibitor treated patients had a significant rise in CD4+ numbers. The marked rise in the CD4+ T cells seen in individuals in this study was not accompanied over a 40-week period by a change in the abnormally low CD4+ naive compartment, and thus was almost completely of memory phenotype. The CD38 expression on CD8+ cells fell during treatment, and decreased to a greater degree than the comparable rise in CD4+ T cell counts. This decrease continued in many patients after the CD4+ T cell rise or viral load decline had plateaued. CONCLUSION: HAART results in changes in activation to a greater extent than absolute changes in CD4+ T cell numbers, but is not accompanied by an increase in naive CD4+ T cells. Measurements of CD4+ T cell numbers alone may not allow appropriate interpretation of immune activation or immune competence in patients receiving those drugs.

Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients.

The safety, tolerability, and antiviral activity of atevirdine (ATV), a nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts < or =500/mm3. In all, 34 HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses chosen to achieve one of three serum trough levels: 5 to 13 microM, 14 to 22 microM, or 23 to 31 microM. Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients. No significant change from baseline in HIV-1 plasma RNA mean copy number was detected at week 4 (+0.09 log10 copies/ml; p = .30). However, some evidence indicated moderate antiviral activity at week 4, based on median changes in CD4 count (+23/mm3; p = .05), and viral peripheral blood mononuclear cell (PBMC) titer (-0.68 log10) copies/ml; p = .03). In addition, 2 of 4 patients with detectable baseline serum p24 antigen showed declines of >50%. HIV-1 resistance to ATV was detected in 41% of patients and was most commonly associated with RT mutations K103N and Y181C. In contrast, the Y181C mutation was not detected in ATV-resistant isolates obtained from patients enrolled in ACTG 199, a study of ATV given in combination with zidovudine. Under the conditions of this study, ATV failed to demonstrate significant antiretroviral activity. However, transient in vivo activity might have been obscured by rapid development of resistance coupled with inadequate sampling at early time points following initiation of ATV therapy.

Mycobacterium szulgai osteomyelitis in an AIDS patient.

Mycobacterium szulgai is a scotochromogen mycobacterium that accounts for < 1% of all human isolates of non-tuberculous mycobacteria. We report the first case of osteomyelitis caused by Mycobacterium szulgai in an AIDS patient. Culture from tissue was needed for isolation and identification of the organism, which was initially misidentified as Mycobacterium gordonae. Susceptibility testing to a fluoroquinolone was carried out and is also reported here for the first time. This case demonstrates the pathogenic potential of M. szulgai in this setting, and illustrates the need to obtain tissue specimens for culture in infected immunosuppressed patients to make a specific microbiological diagnosis and institute appropriate therapy.

Isolation and propagation of human papillomavirus type 16 in human xenografts implanted in the severe combined immunodeficiency mouse.

We report the isolation and propagation of human papillomavirus type 16, the main agent of cervical cancer, using human foreskin fragments implanted in severe combined immunodeficiency mice. The infection produced viral particles, and with each passage of the virus it caused lesions identical to intraepithelial neoplasia, the precursor to carcinoma.

Variability and prognostic values of virologic and CD4 cell measures in human immunodeficiency virus type 1-infected patients with 200-500 CD4 cells/mm(3) (ACTG 175). AIDS Clinical Trials Group Protocol 175 Team.

Virologic measurements are increasingly used to evaluate prognosis and treatment responses in human immunodeficiency virus (HIV) type 1 infection. Markers of HIV-1 replication, including infectious HIV-1 titer from peripheral blood mononuclear cells, serum HIV-1 p24 antigen, plasma HIV-1 RNA, CD4 cell numbers, and viral syncytium-inducing (SI) phenotype, were determined in 391 virology substudy participants in AIDS Clinical Trials Group study 175. The subjects had 200-500 CD4 cells/mm3. All markers of viral replication significantly correlated with one another and were inversely related to CD4 cell number. Disease progression to an AIDS-defining event or death or loss of >50% of CD4 cells was associated with infectious HIV-1 titer (P < .001), HIV-1 RNA (P < .001), and HIV-1 p24 antigen (P = .007). In multivariate proportional hazards models, p24 antigen was never significant when HIV-1 RNA level was included. In a model containing infectious HIV-1 titer (P = .038), HIV-1 RNA (P < .001), SI phenotype (P < .001), and CD4 cell number (P = .18), only the virologic parameters remained significantly associated with progression.

Changes in virologic markers as predictors of CD4 cell decline and progression of disease in human immunodeficiency virus type 1-infected adults treated with nucleosides. AIDS Clinical Trials Group Protocol 175 Team.

The associations of CD4 cell count, plasma human immunodeficiency virus (HIV) type 1 RNA, infectious HIV titer in peripheral blood mononuclear cells, immune complex-disrupted (ICD) p24 antigen, and MT-2 assays with measures of disease progression after drug treatment were assessed in a subset of patients enrolled in AIDS Clinical Trials Group Study 175. Baseline plasma RNA levels and changes in RNA values at weeks 8 or 56 were more important predictors of disease progression than were baseline or changes in CD4 cell counts. Each 10-fold lower HIV RNA concentration at baseline and each 10-fold decrease in HIV RNA between baseline and week 8 was associated with increases of 49-61 CD4 cells/mm3 at weeks 56 and 104. In multivariate analyses, neither baseline values nor changes in infectious HIV titer nor ICD p24 antigen concentrations were associated with long-term changes in CD4 cell count. Plasma HIV-1 RNA appears to be the best predictor of long-term CD4 cell count responses and disease progression.

Results of a screening program for Chlamydia trachomatis infection in men attending a sexually transmitted diseases clinic.

BACKGROUND: Screening programs for Chlamydia trachomatis infection in men are uncommon. GOAL: To report the results of a screening program using the Syva MicroTrak direct fluorescent antibody (DFA) test (Palo Alto, CA) for diagnosis of C. trachomatis infection in men attending a sexually transmitted diseases (STD) clinic. STUDY DESIGN: DFA testing was performed on an additional urethral specimen obtained during male new patient or new complaint visits between July 1, 1994 and June 30, 1996. Positive and negative test results were compared according to patient demographic characteristics, symptoms, diagnoses, and treatments received. RESULTS: 474 of 9,662 (4.9%) DFA tests were positive. Men with chlamydial infection were more likely to be African-American (p < 10(-7)) and less than 24 years of age (p < 10(-7)). C. trachomatis infection was present in 10.7% of those with gonorrhea and 10.0% of those with nongonococcal urethritis. Forty percent of chlamydia cases were asymptomatic, and 97% were treated at the visit owing to existing clinic protocols. CONCLUSIONS: C. trachomatis infection is common and often asymptomatic in men attending STD Clinics. Infected men are likely to be young and African-American. Routine screening with the Syva MicroTrak DFA test will detect unsuspected cases of chlamydial infection; however, in the clinic in this report, most cases were already treated according to standard clinic protocols.

A randomized, double-blind trial of parenteral low dose versus high dose interferon-beta in combination with cryotherapy for treatment of condyloma acuminatum.

Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts. Subjects were randomized to receive subcutaneous injections of either 2 x 10(6) or 4 x 10(6) IU/m2 of IFN-beta (Biogen) three times a week for a total of 6 weeks. Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals. Systemic side- effects were modest in intensity and included fever, chills, myalgia, and headaches (flu-like symptoms). During the first 2 weeks of therapy, they were more common in the high dose group than in the low dose group (P = 0.02). Using survival analysis, there was no significant difference between the two groups in rates of resolution of warts present at baseline (P = 0.62). However, the rate of new lesion formation during the study was significantly lower in the high dose group (P = 0.04).

HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine.

Previous studies have shown that the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase mutation Y181C, which confers high-level resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), develops rarely during therapy with NNRTIs plus zidovudine. To determine whether didanosine (ddI) is also effective in preventing the emergence of Y181C, we analyzed delavirdine (DLV) susceptibilties and reverse transcriptase sequences of isolates obtained from patients enrolled in a pharmacokinetic study of DLV and ddI. Nine NNRTI-naive patients were evaluated. Seven received DLV/ddI and two received DLV/ddI/zidovudine. Median durations of prior zidovudine and ddI were 26 and 15 months, respectively. Isolates from eight of nine patients had a mutation(s) associated with nucleoside resistance at entry. After treatment with DLV and ddI alone, isolates from five of seven patients developed Y181C, four in combination with K103N. Thus, in this group of nucleoside-experienced patients, combination therapy with DLV/ddI did not prevent the emergence of Y181C.

The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team.

BACKGROUND: We studied measures of human immunodeficiency virus (HIV) replication, the viral phenotype, and immune function (CD4 cell counts) and the relation of changes in these indicators to clinical outcomes in a subgroup of patients in a controlled trial of early antiretroviral treatment for HIV, the AIDS Clinical Trials Group Study 175. METHODS: The 391 subjects, each of whom entered the study with a single screening CD4 cell count of 200 to 500 per cubic millimeter, were randomly assigned to receive zidovudine alone, didanosine alone, zidovudine plus didanosine, or zidovudine plus zalcitabine. Plasma concentrations of HIV RNA were assessed in 366 subjects, and viral isolates from 332 subjects were assayed for the presence of the syncytium-inducing phenotype. RESULTS: After eight weeks, the mean (+/-SE) decrease from base line in the concentration of HIV RNA, expressed as the change in the base 10 log of the number of copies per milliliter, was 0.26+/-0.06 for patients treated with zidovudine alone, 0.65+/-0.07 for didanosine alone, 0.93+/-0.10 for zidovudine plus didanosine, and 0.89+/-0.06 for zidovudine plus zalcitabine (P<0.001 for each of the pairwise comparisons with zidovudine alone). Multivariate proportional-hazards models showed that higher base-line concentrations of plasma HIV RNA, less suppression of plasma HIV RNA by treatment, and the presence of the syncytium-inducing phenotype were significantly associated with an increased risk of progression to the acquired immunodeficiency syndrome and death. After adjustment for these measures of viral replication and for the viral phenotype, CD4 cell counts were not significant predictors of clinical outcome. CONCLUSIONS: Both the risk of the progression of HIV disease and the efficacy of antiretroviral therapy are strongly associated with the plasma level of HIV RNA and with the viral phenotype. The changes in the plasma concentration of HIV RNA predict the changes in CD4 cell counts and survival after treatment with reverse-transcriptase inhibitors.

Prognostic value of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in patients with advanced HIV-1 disease and with little or no prior zidovudine therapy. AIDS Clinical Trials Group Protocol 116A/116B/117 Team.

The association of plasma human immunodeficiency virus type 1 (HIV-1) RNA level at study entry and over time with clinical progression was evaluated in 187 patients from AIDS Clinical Trials Group protocol 116A who had little or no prior zidovudine treatment. Three-fold-higher HIV-1 RNA levels at study entry and 3-fold increases by week 8 were associated with progression (relative hazard [RH], 1.67; 95% confidence limits [CL], 1.20, 2.32; and RH, 1.45; CL, 1.02, 2.05, respectively). Having 3-fold-higher CD4 cell count at entry was independently associated with a 52% reduction in risk for progression (adjusted RH, 0.48; CL, 0.33, 0.70). When stratified by length of prior zidovudine therapy, RNA level was predictive in drug-naive patients (adjusted RH, 1.87; CL, 1.23, 2.85) but not predictive in patients with up to 16 weeks of prior therapy (adjusted RH, 1.11; CL, 0.70, 1.76). Analysis suggests that the acquisition of mutations at HIV-1 reverse transcriptase codons 215 and 74 is associated with subsequent increases in HIV-1 RNA level (relative risk, 7.00; CL, 0.86, 56.90).

Therapeutic efficacy and complications of excisional biopsy of condyloma acuminatum.

BACKGROUND AND OBJECTIVES: Among the various treatment modalities for condyloma acuminatum, excisional cold-blade surgery appears excellent but it has been little studied and little used, particularly for lesions not located in the perianal area. GOALS: To examine the efficacy and complications of scissors excision of single anogenital warts. STUDY DESIGN: Retrospective analysis of single warts completely excised with scissors for the purpose of biopsy before patient entry in a randomized, placebo-controlled study of the efficacy and safety of various parenteral interferons in combination with cryotherapy. RESULTS: Of 152 patients entered in the main study, 85 patients were available for analysis. At 4 and 16 weeks after excision, 16 of 85 (19%) and 14 of 68 (21%) of the excised lesions recurred. After at 6 least months of follow-up, 2 of 11 (18%) of the excision sites demonstrated some evidence of pigmentation changes. CONCLUSIONS: Scissors excision of single anogenital warts has a high rate of success and acceptable long-term side-effects.