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PubMed1998

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, and hydroxyurea with granulocyte colony-stimulating factor support for patients with poor-prognosis cancer of the head and neck.

PURPOSE: We have previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (RT) (FHX). In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients. METHODS: Fifty-five patients who had either failed to respond to prior RT (n = 25) or surgery, had a coexistent or prior second malignancy, or who had unresectable or metastatic disease and an expected 2-year survival rate less than 10%, were treated. Chemoradiotherapy consisted of 2 Gy on days 2 to 6 (once-daily RT cohorts) or 1.5 Gy twice a day (hyperfractionated cohorts). Simultaneous HU (500 or 1,000 mg twice per day for 11 doses) and infusional 5-FU (600-800 mg/m2/d for 5 days) were given along with infusional paclitaxel at escalating doses of 5 to 25 mg/m2/d for 5 days. Granulocyte colony-stimulating factor (G-CSF) was administered on days 7 through 13 at 5 microg/kg/d. Cycles were repeated every 14 days until completion of RT. Plasma paclitaxel levels were determined on day 4 of cycle 1. RESULTS: Dose-limiting toxicities (DLTs) consisted of myelosuppression, mucositis, dermatitis, and diarrhea. Plasma concentrations of paclitaxel greater than 10 nmol/L were achieved in 65% of patients at the recommended phase II dose (RPTD) level of paclitaxel. Seventy percent of assessable patients achieved a complete response (CR) to therapy. Twenty patients were treated at the RPTD of HU 500 mg orally twice daily for 11 doses, 5-FU 600 mg/m2/d by continuous infusion for 5 days; and paclitaxel 20 mg/m2/d by continuous infusion for 5 days, with twice-daily RT. CONCLUSION: The addition of infusional paclitaxel and hyperfractionated RT to FHX is feasible. Radiosensitizing levels of paclitaxel are achieved in most patients. The high locoregional control rate of this regimen justifies further investigation in previously untreated patients.

Adult↗

PubMed1998

Cellular pharmacodynamics and plasma pharmacokinetics of parenterally infused hydroxyurea during a phase I clinical trial in chronic myelogenous leukemia.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and antileukemic activity of hydroxyurea (HU) administered intravenously to patients with advanced-phase chronic myelogenous leukemia (CML). Further objectives were to analyze pharmacodynamic effect on deoxynucleotides (dNTPs) and to seek relationships between the decrease in dNTP pools and inhibition of DNA synthesis in CML blasts. PATIENTS AND METHODS: HU (8, 12, 18, 27, and 40 g/m2) was administered intravenously by a 24-hour continuous infusion to 19 adults with CML in blastic or accelerated phase. Plasma levels of HU were analyzed in all patients. To determine the role of HU in inhibiting ribonucleotide reductase, dNTP pools in the leukemia cells were quantitated. Correlations were sought with these parameters and DNA synthesis inhibition measured ex vivo by [3H]thymidine incorporation. RESULTS: The MTD of HU given as a 24-hour infusion was 27 g/m2. The dose-limiting toxicity was mucositis. There was a significant but transient myelosuppression, with nadir counts generally seen 3 to 4 days after the dose. The steady-state concentration of HU in plasma was achieved by 6 hours, and was proportional to the dose. There was a median 57% decrease in the deoxyadenosine triphosphate (dATP) pool in circulating blasts. In contrast, deoxyguanosine triphosphate (dGTP) and pyrimidine dNTPs were not significantly affected. The extent of DNA synthesis inhibition was related to the residual concentrations of intracellular dATP. CONCLUSION: A 24-hour infusion of HU results in significant but transient myelosuppression in advanced-phase CML. The specific decrease of intracellular dATP correlated with the inhibition of DNA synthesis in CML blasts. This pharmacodynamic action of HU provides a rationale for combination with other chemotherapeutic agents, the effects of which could be augmented by the decline in dATP pools.

Adenosine Triphosphate↗

PubMed1999

Radiation therapy with concomitant hydroxyurea and fluorouracil in stage II and III head and neck cancer.

PURPOSE: In 1986, a multi-institutional phase II trial was begun to study the use of chemotherapy with concomitant radiation in patients with stage II and III head and neck cancer. End points were overall survival, progression-free survival, local/regional control, and toxicity in the setting of organ preservation with concomitant treatment. METHODS: Eligible patients with stage II or III disease received chemotherapy and radiation on a 2-week cycle. Chemotherapy consisted of continuous infusion fluorouracil (5-FU) at 800 mg/m2/d for 5 consecutive days (days 1 to 5) and hydroxyurea (HU) at 1 g orally every 12 hours for 13 doses starting the evening before the start of irradiation. Radiation therapy was given as single 1.8- to 2.0-Gy fractions for 5 consecutive days (days 1 to 5) with chemotherapy. Each 5 days of treatment was followed by a 9-day break (days 6 to 14), during which no additional treatment was given. Treatment cycles were repeated until the completion of the planned radiation dose (six to eight cycles). RESULTS: Between 1989 and 1996, 60 patients were enrolled. All patients were eligible for analysis, with a median follow-up of 52 months for surviving patients and 42 months for all patients. Grade 3 to 4 mucositis occurred in 57% of patients. The 5 year-actuarial overall survival, progression-free survival, and local/regional control were 65%, 82%, and 86%, respectively. Eight patients developed local and/or regional recurrence after treatment. Surgical salvage was possible in three of these patients. Thus, the ultimate 5-year local/ regional control was 91%. CONCLUSION: Concomitant radiation and chemotherapy with 5-FU and HU is an effective regimen in patients with stage II and III head and neck cancer. Progression-free survival and local/regional control appear to be superior to expected rates in patients treated with surgery and radiation. Further testing of this regimen in a phase III setting is indicated.

Administration, Oral↗

PubMed1999

Phase II/pharmacodynamic trial of dose-intensive, weekly parenteral hydroxyurea and fluorouracil administered with interferon alfa-2a in patients with refractory malignancies of the gastrointestinal tract.

PURPOSE: Combined depletion of pyrimidine and purine DNA precursors has resulted in therapeutic synergism in vitro. The aims of the current study were to test this strategy in patients with refractory tumors and to assess its effects on selected nucleotide pools. PATIENTS AND METHODS: A single-institution phase II trial was initiated in patients with advanced carcinomas of the stomach and pancreas. Patients had measurable disease and had no prior chemotherapy except adjuvant fluorouracil (5FU) or gemcitabine. 5FU was administered by CADD + pump at 2.6 g/m(2) intravenously by 24-hour infusion on days 1, 8, 15, 22, 29, and 36. Parenteral hydroxyurea (HU) was administered at 4.3 g/m(2) as a 24-hour infusion concurrently with 5FU. Interferon alfa-2a (IFN-alpha2a) was administered at 9 million units subcutaneously on days 1, 3, and 5 each week. No drug was administered in weeks 7 and 8. Pharmacodynamic studies were performed to assess drug effects on levels of deoxyuridine triphosphate (dUTP) and thymidine triphosphate (TTP) pools in peripheral-blood mononuclear cells (PBMCs) before and 6 hours after treatment using a highly sensitive DNA polymerase assay. RESULTS: There were 53 patients enrolled onto the study (gastric carcinoma, 31; pancreatic carcinoma, 22). The median age was 61 years, with 22% of patients > or = 70 years old. The predominant grade 3 to 4 toxicities were leukopenia (49%), granulocytopenia (55%), and thrombocytopenia (22%). Severe diarrhea occurred in 12%, mucositis in 0%, and vomiting in 10% of patients. Patients > or = 70 years had no greater incidence of toxicities. Among the 30 assessable patients with gastric carcinoma, there were two (7%) complete responders and 11 (37%) partial responders (median duration, 7 months). Among the 21 assessable patients with pancreatic carcinoma, there was one responder. Median survival among all patients with gastric carcinoma was 10 months and 13 months for patients with pancreatic carcinoma. Twenty-three patients had samples studied for levels of dUTP and TTP. There was no change in the levels of TTP before and after treatment. Furthermore, dUTP was detected in only five of 28 samples after treatment with no increase in the dUTP/TTP ratio. CONCLUSION: Combination therapy with high-dose, weekly infusional HU and 5FU with IFN-alpha2a modulation was well-tolerated with activity in gastric cancer. Patients > or = 70 years tolerated therapy as well as younger patients. This was the first study to correlate levels of TTP and dUTP after treatment with clinical outcome. In PBMCs used as a surrogate tissue, HU abrogated the 5FU-induced increase in dUTP levels without reversing the overall efficacy of the regimen.

Adult↗

PubMed2001

Concomitant infusional paclitaxel and fluorouracil, oral hydroxyurea, and hyperfractionated radiation for locally advanced squamous head and neck cancer.

PURPOSE: To improve local disease control and survival with organ preservation, we conducted a phase II multi-institutional trial with a concomitant taxane-based chemotherapy and hyperfractionated radiation regimen. PATIENTS AND METHODS: Sixty-four patients with locally advanced squamous cancers (stage IV, 98%; N2/3, 81%) were treated on an intensive regimen consisting of 5-day (120-hour) infusions of paclitaxel (20 mg/m(2)/d) and fluorouracil (600 mg/m(2)/d), oral hydroxyurea 500 mg every 12 hours for 11 doses, and radiation 1.5 Gy bid (T-FH2X). Chemoradiation was administered concomitantly on days 1 to 5 of each 14-day cycle. A full treatment course consisted of five cycles during a 10-week period to a total radiation dose of 72 to 75 Gy. RESULTS: The median follow-up for the group is 34 months. At 3 years, progression-free survival is 63%, locoregional control is 86%, and systemic control is 79%; overall survival is 60%. Seventeen patients died of recurrent cancer, two died of second primary cancers, and four died of other causes. Side effects observed include anemia (22% required transfusion), leucopenia (34%, grade 3 to 4), and mucositis (84%, grade 3 to 4). Organ preservation principles were maintained. At 1 year posttreatment, 61% of patients had severe xerostomia and 47% had compromised swallowing. There was little disturbance of speech quality in 97% of patients at the same follow-up point. CONCLUSION: T-FH2X is a highly active and tolerable concomitant chemotherapy and hyperfractionated radiation regimen that induces sustained local tumor control and holds promise for improved survival with organ preservation in high-risk patients. Identification of less toxic therapy and improved distant disease control are needed. T-FH2X should be tested in a randomized trial and compared with a less intensive concomitant regimen that uses once-daily radiation fractionation.

Administration, Oral↗

PubMed2005

Box-Behnken experimental design in the development of a nasal drug delivery system of model drug hydroxyurea: characterization of viscosity, in vitro drug release, droplet size, and dynamic surface tension.

The purpose of the research was to investigate the changes in physicochemical properties and their influence on nasal formulation performance using 5-factor, 3-level Box-Behnken experimental design on the combined responses of viscosity, droplet size distribution (DSD), and drug release. Gel formulations of hydroxyurea (HU) with surface-active polymers (hydroxyethylcellulose [HEC] and polyethylene-oxide [PEO]) and ionic excipients (sodium chloride and calcium chloride) were prepared using Box-Behnken experimental design. The rheology and dynamic surface tension (DST) of the test formulations was investigated using LV-DV-III Brookfield rheometer and T60 SITA tensiometer, respectively. Droplet size analysis of nasal aerosols was determined by laser diffraction using the Malvern Spraytec with the InnovaSystems actuator. In vitro drug release studies were conducted on Franz diffusion cells. With PEO gel, calcium chloride increased the viscosity and DSD and retarded drug release, while sodium chloride decreased the viscosity, DST, and DSD and accelerated the release of HU. With HEC gel, the addition of the above salts resulted in less significant changes in viscosity, DSD, and DST, but both salts significantly increased the release of HU. Droplet size data obtained from a high viscosity nasal pump was dependent on type of polymer, polymer-excipient interactions, and solvent properties. The applications of Box-Behnken experimental design facilitated the prediction and identified major excipient influences on viscosity, DSD, and in vitro drug release.

Administration, Intranasal↗

PubMed1977

The effects of actinomycin D, puromycin, cycloheximide and hydroxyurea on 3',5,3-triiodo-L-thyronine stimulated 2-deoxy-D-glucose uptake in chick embryo heart cells in vitro.

The uptake of 2-deoxy-D-[1-3H]glucose ([1-3H]DOG) by cultured chick embryo heart cells was stimulated by L-triiodothyronine (T3). This stimulation began with the exposure to T3, rose linearly for about 8 h and reached a plateau around 24h. Actinomycin D, puromycin and cyclohexmide had no effect on the stimulated sugar uptake during the first 6h. These agents prevented the further increase in the rate of [1-3H]DOG uptake in T3-treated cultures that occurred between 6 and 24h. In the presence of hydroxyurea the uptake of [1-3H]DOG in both control and T3-treated cells was unchanged. These results suggest that some of the effects of T3 may not require new synthesis of either RNA, proteins or DNA.

Animals↗

PubMed1991

Regulation of gene expression in choriocarcinoma by methotrexate and hydroxyurea.

Choriocarcinoma, a highly malignant neoplasm of trophoblastic origin, is remarkable for its marked degree of sensitivity to chemotherapeutic agents. We treated two cell lines derived from choriocarcinoma patients with two antineoplastic agents, methotrexate and hydroxyurea (HU), both of which cause nucleotide depletion and have been previously shown to be effective against choriocarcinoma, and found pleiotropic regulation of several genes. Three genes, hCG alpha-subunit, beta-subunit, and placental alkaline phosphatase, were all strongly induced by methotrexate and HU. Expression of c-myc, an oncogene associated with proliferation, was reduced to nearly undetectable levels by the drug treatment, while expression of beta 2-microglobulin, a component of the class 1 major histocompatibility locus, was unchanged. In addition, the mechanism of induction by HU of one of these genes, the hCG alpha-subunit gene, was found to occur at the level of transcription. The similar effects of methotrexate and HU, two mechanistically unrelated antimetabolites, on the induction of specific gene expression in choriocarcinoma cells suggest that these effects are due to nucleotide pool alteration, rather than specific ligand effects. Furthermore, the hCG alpha-subunit promoter contains a transcriptionally regulated HU-responsive element.

Choriocarcinoma↗

PubMed1975

Regulation of FSH secretion: use of hydroxyurea to deplete germinal epithelium.

Hydroxyurea, a chemotherapeutic agent that prevents mitosis by inhibiting DNA synthesis, was administered to adult male rats for 70 days. Plasma FSH and LH showed no systematic trend although severe germinal cell depletion was produced. These data suggest that the cell(s) of the seminiferous tubule involved in FSH regulation must be either the type A spermatogonium or the Sertoli cell.

Animals↗

PubMed1984

5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group.

Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival.

Adolescent↗

PubMed1988

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine.

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.

Adolescent↗

PubMed2006

Calcium channel antagonists augment hydroxyurea- and ru486-induced inhibition of meningioma growth in vivo and in vitro.

OBJECTIVE: Although the chemotherapy drug hydroxyurea (HU) and the antiprogesterone mifepristone (RU486) have been used to treat meningiomas for which surgical and radiation therapies have failed, results have been disappointing. The addition of calcium channel antagonists (CCAs) to chemotherapeutic drugs enhances tumor growth inhibition in other tumor types, and the authors demonstrated that CCAs can block meningioma growth in vitro and in vivo. The purpose of this study was to test the effects of the addition of a CCA to HU or RU486 on meningioma growth. METHODS: Primary and malignant (IOMM-Lee) meningioma cell lines were treated with HU, RU486, or either of these plus diltiazem or verapamil. Assays for cell growth, apoptosis, and fluorescent-activated cell sorting were performed on in vitro cultures. Similar cell lines were implanted into nude mice and were treated with HU or RU486, in combination with a CCA. Tumors were analyzed by light microscopy, MIB-1, and factor VIII immunohistochemical staining studies. RESULTS: The addition of diltiazem or verapamil to HU or RU486 augmented meningioma growth inhibition by 20 to 60% in vitro. In vivo, tumors treated with combination drugs were smaller; and immunohistochemical analysis of the IOMM-Lee tumors showed a 10% decrease in the MIB-1 ratio (from 0.41 to 0.30) and an approximate 75% decrease in microvascular density. CONCLUSION: The addition of diltiazem or verapamil to HU or RU486 augments meningioma growth inhibition in vitro by inducing apoptosis and G1 cell-cycle arrest. The combination of HU and diltiazem inhibited the growth of meningiomas in vivo by decreasing proliferation and microvascular density. These results suggest a possible role for these drugs as an additional adjuvant therapy for recurrent or unresectable meningiomas.

Aged↗

PubMed1989

Synergistic effects of hydroxyurea and thymidine on the growth inhibition of V79 cells.

The effects of hydroxyurea (HU) and thymidine (TdR) on cell cycle progression in V79 Chinese hamster lung cells were examined by flow cytometry. Suppression of the cell cycle progress rate by HU was further enhanced by the combination of a low concentration of TdR and HU as compared to that induced by TdR alone; i.e., these drugs were shown to have a synergistic effect. It was concluded that the presence of TdR was effective in assisting HU-induced suppression of DNA synthesis.

Animals↗

PubMed1989

Effects of hydroxyurea on the phagocytosis of microspheres in V79 cells.

Phagocytosis of fluorescent microspheres in V79 cells arrested in the S phase by hydroxyurea (HU) was investigated by flow cytometry. The phagocytic activity increased with the exposure time of HU. No dependency on the HU concentration was observed in the concentration used. Cell size (projection area) and membrane fluidity, two factors effected by HU treatment, were examined in relation to phagocytic activity, and were found to be significantly increased. The elevation in phagocytic activity could be interpreted in terms of the alteration in the two physiological factors.

Animals↗

PubMed1983

Limb deformity induced in chick embryo by hydroxyurea.

After a dose of 800 micrograms of hydroxyurea (HU) was administered to day-4 chick embryos in ovo, the limb deformity including micromelia was observed. We examined the teratogenic mechanism of the action for HU by using histochemical and biochemical techniques. The present study provides histological evidence for the cell death and the depression of cell proliferation just after the treatment with HU and the retardation in periosteal ossification during the process of repair and/or recovery from cell death. On the other hand, the incorporation of [3H]glucosamine and [35S]sulfate into glycosaminoglycan was inhibited at day-7 and day-9, when the embryos are in the process of repair and/or recovery. The cartilage specific proteoglycan, an index of chondrogenesis, appeared at day-7, but the ratio of cartilagenous proteoglycan/noncartilagenous proteoglycan in the treated limbs was depressed. These results suggest that the slight retardation in chondrogenesis and/or the incomplete function of chondrocyte were induced by the treatment with HU in chick embryos. It is considered from above observation that the retardation in chondrogenesis and osteogenesis caused during the repair and/or recovery process of cell death brought about the limb deformity; shortening, thinning and bending of hind limbs.

Animals↗

PubMed1992

Concomitant chemoradiotherapy with cisplatin, 5-fluorouracil and hydroxyurea in poor-prognosis head and neck cancer.

Based on encouraging results with 5-fluorouracil (5-FU), hydroxyurea, and concomitant radiotherapy in patients with advanced or recurrent head and neck cancer, an attempt was made to modulate the regimen by the addition of cisplatin as a third active agent. A cohort of 26 patients with head and neck cancer of all histologies were entered into a broad phase I study investigating simultaneous radiation therapy, 5-FU (with or without leucovorin), HU, and infusional cisplatin administered on an alternate-week schedule. Eleven patients (group 1) had failed prior curative local therapy and 15 patients (group 2) were considered to have a poor prognosis with standard therapy. The median follow-up was 30 months. The response rate for all evaluable patients was 82% (14/17), and the complete response rate was 65% (11/17). Patients in group 1 demonstrated a high failure rate (9/11), while few group 2 patients failed after treatment (2/15). The median time to progression was 4.4 months in group 1 and has not been reached in group 2. Patients in group 1 failed locally (7/11), while no local failures were observed in group 2. Acute and cumulative hematologic toxicity was encountered at all dose levels and schedules tested and prevented escalation of the cisplatin dose beyond the desired level of 100 mg/m2 per months. Mucositis was a second significant toxicity in patients with head and neck cancer and was more pronounced during cycles containing leucovorin. A detailed analysis of survival, time to progression, and site of failure is presented.

Adult↗

PubMedDate not supplied

The effect of hydroxyurea on the phosphorylation of zidovudine and lamivudine in human umbilical vein endothelial cells.

The purpose of this study was to characterize the activation of zidovudine (ZDV) and lamivudine (3TC) in human umbilical vein endothelial cells (HUVEC) with and without hydroxyurea (HU) pretreatment. HUVEC were pretreated with HU or control media for 24 h and then incubated for an additional 3 h with ZDV or 3TC. Intracellular concentrations of parent drugs and the phosphorylated forms were determined by high-performance liquid chromatography. Pretreatment with HU resulted in more than a threefold increase in intracellular concentrations of total ZDV, with the major intracellular form being the monophosphate (>80%). The relative percentage of each ZDV form was similar between control and HU-treated cells. On the other hand, intracellular concentrations of total 3TC increased only slightly (14%) with HU pretreatment. Although the parent drug remained the major intracellular form of 3TC, there was nearly a 400% increase in the 3TC triphosphate after HU pretreatment. These data demonstrate that HU causes a large increase in the intracellular accumulation of total ZDV, whereas it increases total 3TC only slightly but improves its triphosphorylation. Given the increase in intracellular concentrations of ZDV monophosphate after HU pretreatment and that the monophosphate has no antiviral activity but is associated with toxicity, the use of HU is not a good strategy to improve ZDV activation in human endothelium. There is improved production of the active antiviral 3TC triphosphate with HU pretreatment. The combination may be beneficial in treating potential sanctuary sites such as endothelium.

Anti-HIV Agents↗

PubMedDate not supplied

Hydroxyurea plus didanosine as maintenance therapy for HIV-infected patients on long-term successful highly active antiretroviral therapy.

BACKGROUND: Toxicity and quality of life issues have moved to delay the initiation of highly active antiretroviral therapy (HAART) and to explore novel treatment strategies for HIV infection. The switch to simpler regimens or treatment discontinuation has been attempted with limited success. The combination of hydroxyurea (HU) plus didanosine (ddI) is a simple regimen that might be able to restrain virus replication for long periods of time and could be an acceptable option as maintenance therapy in patients on prolonged successful HAART. METHOD: The combination of HU (500 mg bid) plus ddI (400 mg qd) was offered to participants with viral load (VL) <50 HIV RNA copies/mL and CD4 counts >350 cells/microL for more than 6 months under HAART. The prior HAART regimen was resumed if VL rose to >5,000 copies/mL and/or the CD4 count fell to <200 cells/microL after being on HU + ddI maintenance therapy. RESULTS: A total of 187 participants replaced HAART with HU + ddI. In an intent-to-treat analysis at 48 weeks, 109 (58%) and 77 (41%) patients had VL below 5,000 and 500 HIV RNA copies/mL, respectively. The mean CD4 count dropped from 809 +/- 283 to 573 +/- 270 cells/microL, while 77% of patients remained above 350 cells/microL. The proportion of participants with hypercholesterolemia declined from 70% to 46% (p <.001), while those with hypertriglyceridemia fell from 36% to 21% (p <.05). Significant improvements in lipohypertrophy and lipoatrophy were observed in 52% and 64% of participants, respectively. Grade 3-4 toxicities appeared in 20 patients (11%), including 3 cases of pancreatitis and 1 of peripheral neuropathy. Prior history of VL >5 log, CD4 counts <200 cells/microL, and ddI experience were independently associated with lower response to HU + ddI maintenance therapy. CONCLUSION: The combination of HU + ddI may be a satisfactory maintenance therapy for more than half of patients on successful HAART who want to alleviate drug-related toxicities and/or pill burden. Patients with metabolic and/or body-shape abnormalities might particularly benefit from switching to this simple regimen.

Adult↗