Most of the biologic filler materials that increase the thickness of the corium in a wrinkle line are phagocytosed within a certain time. Therefore, a lasting effect can only be achieved with nonresorbable synthetic substances. Artefill consists of 20 volume percent microspheres of polymethyl‐methacrylate and 80 volume percent of bovine collagen. Beneath the crease, the microspheres with their exceptional surface smoothness stimulate fibroblasts to encapsulate each individual one of the 6‐million microspheres contained in 1 mL of Artefill. Collagen is merely a carrier substance that prevents the microspheres from agglomerating during tissue ingrowth. The 20 volume percent of microspheres in Artefill provides the scaffold for the 80% volume of connective tissue deposition, a complete replacement of the injected collagen. The filler material beneath a crease acts like a splint and prevents the possibility of its further folding, thereby allowing the diminished thickness of the corium in a crease to recover. This recovery process is well known even in older patients with facial paralysis or after a stroke, whose facial wrinkles and furrows on the paralyzed side disappear over time.

Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog IIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 34 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined ict mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection.The reverse transcriptase (RT) encoded by human immunodeficiency virus type 1 (HIV-1) catalyzes the conversion of the viral genomic RNA into proviral DNA (1, 2). Since RT is essential for virus replication and has no closely related identified cellular homolog, it has been the prime target for antiviral therapy against theacquired immunodeficiency syndrome (AIDS; refs. 3 and 4). This strategy is appropriate since 3'-azido-2',3'-dideoxythymidine (AZT), a nucleoside analog inhibitor of reverse transcription, was the first drug shown to benefit HIV-1-infected individuals (5). Other nucleoside analog RT inhibitors also show promise in clinical evaluations (6, 7). However, the administration of these drugs to patients is usually limited by serious toxicities (7,8). In addition, HIV-1 with reduced AZT-sensitivity has been obtained from AZT-treated patients, suggesting the emergence of resistant virus will limit the drug's efficacy (9, 10). Thus, effective prolonged treatment of HIV-1 infection likely requires the discovery of other, perhaps multiple, RT inhibitors. To this end, we and others (11, 12) have sought to identify other nonnucleoside HIV-1 RT inhibitors. MATERIALS AND METHODSCell Culture and Virus Infections. The cell cultures were maintained at 370C in 5% C02/95% air. The HIV-1 infectivity studies were conducted in MT-2 cells, peripheral blood mononuclear cells (PBMC), and H9 cells as described (9,(13)(14)(15). In brief, MT-2 or H9 cells were infected with HIV-1 (IlIb isolate) at a multiplicity of infection of 0.001. In MT-2 cells syncytium formation was determined 4 days after infection at the peak of the viral cytopathic effect (13). In H9 cells, growth medium with fresh drug was replaced every 3-4 days, and at 14 days-...

ArteFill, the successor product to Artecoll, is an injectable wrinkle filler composed of polymethylmethacrylate microspheres and bovine collagen, which offers long-lasting and probably permanent augmentation of wrinkles and skin contour deformities. The pivotal U.S. Food and Drug Administration study consisted of 251 subjects at eight centers in the United States who received injections of ArteFill or bovine collagen dermal filler (control) in 1334 wrinkles of the glabella, nasolabial folds, radial upper lip lines, and corners of the mouth. The efficacy data generated by masked observers using a photographic Facial Fold Assessment Scale demonstrated a significant improvement with ArteFill compared with collagen at 6 months (p < 0.001) in the nasolabial folds. In the ArteFill group, 12-month follow-up was obtained for 111 subjects (86.7 percent) and showed persistence of significant wrinkle correction. A subgroup of 69 patients who received ArteFill were recalled 4 to 5 years later. Five patients reported six late adverse events that occurred from 2 to 5 years after the initial injection; four of the adverse events were mild cases of lumpiness and two were severe. The total number of late adverse events was six of 272 (2.2 percent) wrinkles injected. Among the 272 wrinkles evaluated at 5 years, two events (0.7 percent) in one patient were rated as severe (a nodular, minimally inflammatory to noninflammatory reaction in both nasolabial folds). Investigator Facial Fold Assessment ratings at 4 to 5 years were improved from baseline by 1.67 points (p < 0.001).