Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Indinavir”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMedDate not supplied

Different outcomes in patients achieving complete or partial viral load suppression on antiretroviral therapy.

BACKGROUND: Potent combination antiretroviral therapy can reduce HIV plasma viral load (VL) to levels below the detection limit for as long as 2 years or more. A VL <500 HIV RNA copies/mL was until recently considered a reasonable therapeutic goal. However, lower levels seem necessary if VL rebounds and development of drug resistance are to be avoided. PATIENTS AND METHODS: The clinical and virologic outcome at 1 year were prospectively examined in a group of 100 patients who began a triple combination antiretroviral therapy regimen consisting of stavudine (d4T), lamivudine (3TC), and indinavir (IDV). A modified ultrasensitive VL test with a detection limit of 40 copies/mL and a point mutation nested polymerase chain reaction (PCR) assay for detecting the codon 184 mutation conferring 3TC resistance were used for testing samples collected longitudinally from these individuals. RESULTS: Overall, VL values <40 copies/mL were reached in 45% and 32% of patients at nadir and at 12 months, respectively. More than half (24 of 45 persons) who achieved a level <40 copies/mL at nadir remained with undetectable VL at 1 year, whereas this occurred in only one fourth (7 of 28 persons) of those having levels of 40 to 500 copies/mL (P < .05). However, rebounds in VL to >500 copies/mL at 1 year were seen at similar rates (26.6% and 25%, respectively) in persons achieving either complete (<40 copies/mL) or partial (40-500 copies/mL) VL suppression at nadir. In contrast, the codon 184 mutation emerged more frequently at 1 year in patients whose VL remained between 40 and 500 copies/mL at nadir than in those who reached a level <40 copies/mL (30.7% versus 0%; P < .05). CONCLUSION: Plasma VL at nadir after beginning highly active antiretroviral therapy (HAART) predicts the 1-year outcome. The achievement of levels of viremia <40 copies/mL are desirable during antiretroviral therapy if prolonged benefit is to be obtained. Because more than two thirds of persons with residual viremia do not show drug resistance, intensification strategies should be investigated for those patients with a good virologic response but without complete suppression during the first 6 months on HAART.

Adult↗
PubMed2000

[Antiretroviral therapy in HIV infection. Effects of the introduction of new drugs on health care expenditures, 1994-1999].

The administration of antiretroviral compounds to our cohort of HIV-infected patients was assessed since 1994, on the ground of some epidemiological, clinical, and therapeutic variables. During the six-year study period, a significant increase of mean prescription rate of overall anti-HIV agents was observed, with a nearly 10-fold rise of mean prescribed daily doses per 1,000 patients-year. In particular, lamivudine and indinavir represented the most frequently administered drugs, among nucleoside analogues and protease inhibitors, respectively. A significant increase of the percentage of HIV-infected patients undergoing combined antiretroviral therapy (79.3% in 1999), and the mean number of drugs prescribed per patient (3.02 in 1999), was concurrently detected. The progressive changes of antiretroviral therapy guidelines were responsible for a nearly 16-fold increase of expenditures directly related to antiretroviral drug administration in 1999 compared with 1994 (with over 41% of costs related to protease inhibitors). On the other hand, a substantial modification of HIV disease evolution occurred in our patient cohort in terms of absolute morbidity and mortality figures, as expressed by a drop of notified AIDS cases and AIDS-related deaths ranging from 2.5 to 5 times, during the considered period.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy].

We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML.

Acquired Immunodeficiency Syndrome↗
PubMed2002

[Acute coronary syndromes in patients treated with HIV protease inhibitors].

INTRODUCTION: Cardiovascular complications occurring in patients infected by the human immunodeficient virus (HIV) have considerably changed since the appearance, in April 1996, of highly active antiretroviral tri-therapy (HAART), associating reverse transcriptase and protease HIV-1 inhibitors. The spectacular efficacy of anti-proteases has led to the almost complete disappearance of these opportunistic complications. However, in May 1998, acute coronary accidents were reported in the literature, thus questioning the possible responsibility of antiprotease treatment in the occurrence of accelerated atheroma. METHOD: We report a series of 8 seropositive patients in whom an acute coronary event had occurred between February 1997 and February 1999. RESULTS: The patients were young and all exhibited cardiovascular risk factors (smoking, dyslipidemia) and were treated with HIV-1 protease inhibitors. Six patients presented myocardial infarction, one patient unstable angina and one patient effort angina. COMMENTS: A rise in triglycerides was observed principally on ingestion of ritonavir and a rise in cholesterol and LDL-cholesterol with all the antiprotease agents. Glucose intolerance was observed with indinavir. The occurrence of acute coronary events appeared to be related to antiprotease treatment (at the origin of metabolic disorders, endothelial dysfunction...), although it was impossible to say whether the antiprotease agents were responsible for the early atheroma or whether they simply contributed to the event. The coronary lesions were characterized by their number (single artery) and their topography (proximal or median). Nelfinavir may carry less cardiovascular risks than the other antiproteases. Mean term prognosis was relatively good, after therapeutic adjustment (change in antiprotease, strategic measures against cardiovascular risk factors, introduction of anti-anginal treatment...). CONCLUSION: Larger and longer studies would help to specify the role of antiproteases in the occurrence of early coronary events. Rigorous monitoring (lipid and glucose measurements, tests to search for myocardial infarction,..) together with the development of new antiretroviral molecules would reduce the number of coronary events in this type of patient.

Adult↗
PubMed2002

[Post-exposure prophylaxis in Zambia; the experiences of a tropical disease specialist following a cut accidentally incurred while operating on an HIV positive patient].

The author, a 33-year-old man employed as a tropical diseases specialist in Zambia, accidentally cut himself during an operation on an HIV positive patient. After washing the wound, he took zidovudine and lamivudine and, on the advice of a counsellor and following logistical discussions with the Dutch Embassy, indinavir as well. Blood test results for HIV antibodies on the day of the accident, after 1 month and after 3 months were negative. After six months, two Zambian tests were positive and two Dutch tests negative. A confirmative test in the Netherlands using blood flown over from Zambia was negative for both anti-HIV and HIV RNA. For health professionals working abroad, there is a protocol for post-exposure prophylaxis. However, improvements to this can be made, for example, how and where diagnostic tests are carried out and where reliable HIV tests are carried out.

Adult↗
PubMedDate not supplied

Successful simplification of HAART in patients with acute primary HIV infection.

Aggressive treatment has been advocated for the management of primary HIV infection (PHI), but the composition and the optimal duration of therapy are still to be determined. In addition, time to undetectable viral load (VL), rate and duration of VL suppression as well as subsequent therapeutic choices remain issues widely debated. We evaluated the rate and duration of VL suppression in 12 consecutive patients with PHI given triple-drug treatment with zidovudine, lamivudine and indinavir (highly active antiretroviral therapy, HAART) at onset of the acute illness and subsequently switched to a simplified 2-NRTI-based regimen once VL suppression was maintained for at least 6 months. Throughout the study, no patient discontinued treatment because of symptoms attributed to the study medications. In the study population, undetectable VL was achieved after a median of 84 days (range: 67-135) on HAART and was maintained for a median of 194 days (range: 179-205) before simplification. After switching to simplified maintenace, undetectable VL was maintained in all patients for at least 6 months. Only one patient experienced virological failure, plasma HIV-RNA remaining suppressed for a median foliow-up of 33 months (15-54) and T-CD4+ being steadily higher than 500/mL in the remaining patients. Our results suggest that simplification of HAART in patients promptly treated during PHI and maintaining undetectable VL for at least 6 months before simplification may be a valid option capable of controlling viral replication and maintaining an optimal immunological profile for a prolonged time.

Adult↗
PubMed2003

Inhibition of TNF-alpha mediated cell death by HIV-1 specific protease inhibitors.

HIV-1 protease inhibitors have contributed significantly to the reduction in morbidity and mortality associated with HIV-1 disease. Some of their clinical benefit may be attributed to inhibition of non-viral pathogen proteases and mammalian proteases involved in apoptosis. Our objective was to investigate the effect of HIV-1 protease inhibitors on two different mechanisms of apoptosis in cells not exposed to HIV-1. Modulation of apoptosis induced in U937 or Jurkat cells by CD95 (Fas-ligand) or TNF-alpha was measured using flow cytometry using the 7-AAD and annexin/propidium iodide methods. - HIV-1 protease inhibitors reduced TNF-alpha mediated cell death in a dose-dependent manner, with a maximum inhibition ranging between 38% and 60% observed for 100 microM indinavir. Saquinavir and ritonavir, but not nelfinavir also inhibited TNF-alpha induced cell death. Nevirapine (an HIV-1 reverse transcriptase inhibitor) showed no effect. The TNF-alpha activity was also inhibited by the caspase inhibitors Z-VAD-fmk at concentrations of 10 microM or less, and by DEVD-cmk. In contrast, HIV-1 protease inhibitors did not affect CD95 induced apoptosis in Jurkat cells at any of the concentrations tested. Our findings indicate that HIV-1 protease inhibitors may act on mammalian proteases involved in the regulation of apoptosis; whether this is relevant in the clinical setting remains to be established. Identification of the pathways involved may lead to a better understanding of the clinical impact of this drug class and their role in HAART associated toxicities.

Antineoplastic Agents↗
PubMed2002

[HIV genotypic mutation selectively induced by the protease inhibitor nelfinavir at codon 30. Case series and consequences for antiretroviral management].

In a survey of 247 HIV-infected patients which received at least six months of combined antiretroviral therapy including the protease inhibitor nelfinavir during the last two years (2000-2001), the specific primary genotypic mutation D30N (with or without the minor mutation N88D), was detected in only four of the 149 (2.7%) subjects who received genotypization after virological failure. Three of these cases of primary nelfinavir resistance occurred among the 84 patients who were protease inhibitor- and/or non-nucleoside reverse transcriptase inhibitor-na ve, while the last episode was registered in a female patient treated since five years, who received an indinavir-based therapy of nearly 12-month duration (interrupted because of untoward kidney effects). During the subsequent follow-up, the substitution of nelfinavir had a favourable laboratory and clinical outcome in all reported patients who continued a different highly active anti-HIV treatment, while a significantly less positive virological and immunological response was seen in all the remaining subjects, and especially in those who experienced virological failure after undergoing at least two prior changes of combined antiretroviral therapy, and were borne by a broad spectrum of protease gene mutations (save those regarding codons 30 and 88). Due to its exclusive resistance pattern, nelfinavir may represent a favorable first-line choice among protease inhibitor-based regimens, since it may spare further treatment options even in the same pharmacological class. In fact, cross-resistance with other protease inhibitors may be limited also in patients experiencing prior long-term antiretroviral therapy, from second-line to rescue regimens, provided that they were pre-treated with drugs other than nelfinavir.

Anti-HIV Agents↗
PubMed2003

Antiretroviral therapy in HIV-2-infected patients: changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of patients treated in Abidjan, Côte d'Ivoire.

OBJECTIVE: To describe changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of HIV-2-infected patients receiving antiretroviral (ARV) therapy in Abidjan, Côte d'Ivoire. METHODS: Consecutive blood samples were collected from 18 HIV-2-infected ARV-naive patients who had received ARV therapy in the UNAIDS drug access initiative (UNAIDS-DAI) in Abidjan between August 1998 and July 2000. Changes in HIV-2 plasma viral load, CD4+ cell counts, and genotypic and phenotypic drug resistance testing were determined. RESULTS: At baseline, 11 (61%) of the 18 patients initiated highly active antiretroviral therapy (HAART) and seven (39%) received dual therapy. No significant change in median viral load was observed at 2 months (P = 0.09), at 6 months (P = 0.06), and at 12 months of therapy (P = 0.26). No significant increase in CD4+ cell counts was observed at 12 months (P = 0.10). All four patients on indinavir-containing HAART had undetectable viral loads at 2-4 months of therapy. However, none of seven patients on nelfinavir-containing HAART had a substantial decrease in viral load. Viruses from 14 patients were analyzed, 12 of which (86%) had at least one primary resistance mutation that is known to confer resistance to HIV-1 virus. Three patients had the multi-drug-resistant mutation, Q151M, two of whom showed reduced susceptibility to zidovudine, didanosine, stavudine and zalcitabine. CONCLUSION: Our limited findings show that nelfinavir-containing regimens may have limited virologic benefit to HIV-2-infected patients.

Adult↗
PubMed2004

Strategies to decrease viral load rebound, and prevent loss of CD4 and onset of resistance during structured treatment interruptions.

BACKGROUND: Toxicity and other drug adherence-related factors have contributed to decreased compliance to antiretroviral regimens amongst HIV-infected patients. Irregular therapy disruption causes loss of CD4 T cells, onset of drug resistance and rapid rebound of plasma viral load (VL). However, an appropriate choice of drugs and properly scheduled structured treatment interruptions (STIs) may limit VL rebound, maintain CD4 counts and minimize resistance. METHODS: We conducted a clinical study of STIs, RIGHT 901, involving 60 drug-naive patients with chronic HIV infection (CD4 >300, VL >10,000) randomized to receive didanosine-stavudine-indinavir (IDV group) or didanosine-stavudine-hydroxyurea (HU group), for 12 weeks. Subsequently, all patients were randomized again to start STI (short induction) or to continue the therapy for an additional 24 weeks before starting STI (long induction). Both groups underwent four STI cycles and then stopped therapy as long as viraemia remained below 10,000 copies/ml before reinitiating another four cycles of STI. RESULTS: During continuous therapy VLs were suppressed at similar rates in both the HU and IDV groups, while a blunted CD4 count was documented in the HU group. Following the first stop median VL rebounded close to baseline values in both groups, however, during the following STI median VL rebound decreased in the HU group, while in the IDV group VL continued to rebound to values close to baseline, and the difference between the two groups was statistically significant. Moreover, patients treated with HU had a constant and stable CD4 increase during STI, whereas CD4 counts fluctuated in the IDV group, with sharp falls during treatment interruptions and partial CD4 recovery following treatment restart. Even in the presence of IDV resistance predisposing mutations at baseline, no genotypic change in the protease sequence was observed during STI. A relevant mutation in the reverse transcriptase sequence (K70R) emerged in one patient interrupting treatment after 36 weeks of continuous therapy and in one patient after four STI cycles. Side effects (no major events) were similar among groups. CONCLUSIONS: An appropriate choice of STI schedule and regimens containing drugs less prone to resistance and/or able to prevent CD4 fluctuation may contribute to optimizing STI for chronically infected patients with respect to limiting viral rebound, improving CD4 counts and maintaining a resistance profile comparable to continuous highly active antiretroviral therapy.

Anti-HIV Agents↗
PubMed2004

The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients.

Although protease inhibitors (PIs) have dramatically improved outcomes in HIV-infected patients, half still fail treatment with PI-based combination therapy. Genetic pressure from incomplete viral suppression rapidly selects for HIV variants with protease gene mutations that confer reduced susceptibility to PI drugs. A number of specific amino acid substitutions have been associated with PI resistance. However, high-level resistance to individual PIs requires the accumulation of several primary and secondary mutations, developing along drug-specific, step-wise pathways. HIV variants resistant to saquinavir and ritonavir usually contain L90M and V82A substitutions, respectively. Indinavir resistance may be linked to substitutions at positions 46 or 82. Resistance to nelfinavir is primarily associated with D30N but may alternatively be found with L90M. Resistance during exposure to amprenavir can follow development of I50V, which also may confer resistance to lopinavir. Failure during treatment with atazanavir is closely linked to 150L. The overlapping of these pathways can lead to multiple-PI resistance, limiting therapeutic options in antiretroviral-experienced patients. Reduced susceptibility to more than one PI is most likely to be associated with amino acid substitutions at six positions: 10, 46, 54, 82, 84 and 90. Other mutations (D30N, G48V, I50V or I50L) are relatively specific for particular PIs and are less likely to produce cross resistance. Certain resistance mutations selected by exposure to one PI may actually increase susceptibility to others. Patients newly diagnosed with HIV infection are increasingly found to harbour virus that is resistant to the more commonly used drugs. Newer PIs may select for mutations that result in less cross resistance with older agents.

Amino Acid Substitution↗
PubMed2005

Incidence of pancreatitis in HIV-1-infected individuals enrolled in 20 adult AIDS clinical trials group studies: lessons learned.

OBJECTIVE: To report on the incidence of clinical- and laboratory-defined pancreatitis in HIV-1-infected individuals treated with antiretrovirals (ARVs). METHODS: Pancreatitis incidence rates were calculated based on a Poisson distribution for subjects enrolled in 1 or more of 20 Adult AIDS Clinical Trials Group studies from October 1989 through July 1999. RESULTS: A total of 8451 subjects were enrolled. The overall pancreatitis rates were 0.61 per 100 person-years (PYs) clinical and 2.23 per 100 PYs clinical/laboratory. Pancreatitis rates for single, dual, and triple nucleoside reverse transcriptase inhibitors (NRTIs) were similar. Rates of pancreatitis in didanosine (ddI) arms seemed to be dose dependent. Pancreatitis rates in ddI/hydroxyurea (HU) arms were not significantly different from the rates for ddI alone. Overall pancreatitis rates for ddI/stavudine (d4T) trials were high at 4.16 per 100 PYs clinical and 6.25 per 100 PYs clinical/laboratory. The highest rates were seen with the combination of indinavir (IDV)/ddI/d4T with or without HU. CONCLUSIONS: The combination of NRTIs and definition has an impact on the incidence of pancreatitis. Standardization of definition and more comprehensive evaluations are needed to determine how much of this pancreatitis is directly caused by ARVs and how much is attributable to preexisting comorbidities and other known risk factors.

Acquired Immunodeficiency Syndrome↗
PubMed2005

[Outcome of HIV-infected patients after 5 years of antiretroviral therapy including a protease inhibitor: the Aproco/Copilote Cohort].

During 2 periods between 1997 and 1999, the Aproco-Copilote (ANRS CO 008) cohort enrolled all HIV-infected patients who began antiretroviral therapy containing a PI in 47 French centers and who volunteered to participate (1281 patients) in order to describe and analyze their long-term clinical course and the benefits of treatment. Complete adherence (more than 95% of drugs actually taken) during the first 4 months of therapy appears crucial in maintaining virological response to therapy over time. Adherence depends on how patients experience the treatment but also on external factors such as their relationship with physicians and social workers. Virological failures were classified in two groups: those sensitive to the PI prescribed and related to poor adherence (no detectable PI) or patients with resistance related to pharmacokinetic issues (detectable but insufficient PI levels). Between April 1997 and May 2004, 118 patients died, and 188 episodes of AIDS and 1178 other severe events were recorded. Follow-up at 5 years was estimated at 90% and the probability of progression towards a new episode of AIDS 16%. Risk of AIDS onset was greatest during the first year and declined thereafter. Severe morbidity unrelated to AIDS or the side effects of treatment was frequent and gradually predominated. The only patients for whom AIDS was the most frequent severe morbidity were those who started treatment with CD4 cell counts < 50/mm3. The cumulative probability of a serious antiretroviral-induced adverse event (mainly hypertransaminasemia) was 30% at 5 years; 2/3 of these events occurred during the first 6 months of follow-up. Factors associated with the 169 events attributed to the first PI prescribed included: plasma HIV RNA >100,000 copies/ml, increased transaminase levels, creatinine clearance <70 ml/min, HCV or HBV co-infection, and prescription of indinavir. Other studies are underway on the associated factors specific to each of the events to delineate the respective roles of the virus, the treatments and other factors.

Adult↗
PubMed2006

Investigation of baseline susceptibility to protease inhibitors in HIV-1 subtypes C, F, G and CRF02_AG.

OBJECTIVE: To compare baseline susceptibility to protease inhibitors among HIV-1 isolates of subtypes C, F, G and CRF02_AG, and to identify polymorphisms that determine the differences in susceptibility. METHODS: A total of 42 samples of drug-naive patients infected with subtypes G (n=19), CRF02_AG (n = 10), F (n = 6) and C (n = 7) were phenotyped and genotyped with the Antivirogram and the ViroSeq 2.0 genotyping system, respectively. A Bayesian network approach was used for a preliminary analysis of the collected data and the dependencies indicated by the network were statistically confirmed. RESULTS: CRF02_AG samples were found to be more susceptible to nelfinavir and ritonavir than other subtypes. Hypersusceptibility to these drugs was associated with the 70R polymorphism. 37D/S/T was associated with reduced susceptibility to indinavir and 89M with reduced susceptibility to lopinavir. Susceptibility to tipranavir was the lowest among the subtype F samples and the highest for subtype G samples, with samples carrying 57R being more susceptible than samples carrying 57K. CONCLUSIONS: Our study suggests that there are baseline susceptibility differences between subtypes and these differences are due to naturally occurring polymorphisms in these subtypes. The predictive value for phenotype of these polymorphisms was even valid in subtypes where these polymorphisms are less prevalent. Taking into account such polymorphisms should improve current algorithms for interpretation of genotyping results in a subtype-independent way.

Algorithms↗
PubMed1996

New drugs for HIV infection.

The US Food and Drug Administration (FDA) has approved the marketing of five new drugs for treatment of HIV infection. Stavudine (D4T; Zerit -- Bristol-Myers Squibb) and lamivudine (3TC; Epivir -- Glaxo Wellcome) are nucleoside analogs similar to zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC). Saquinavir (Invirase -- Roche), ritonavir (Norvir -- Abbott) and indinavir (Crixivan -- Merck) are protease inhibitors, a new class of anti-HIV drugs.

Antiviral Agents↗
PubMed1997

Antiretroviral therapy: a guide to the most important trials.

AIDS and HIV infection have stimulated an unprecedented amount of research. In this review we have selected a few publications illustrating key issues. Viral load monitoring is useful because short-term changes in viremia, caused by antiretroviral treatment, predict long-term outcome. Combination therapy with AZT plus either ddl or ddC produces better results than therapy with AZT only, but the differences are slight and appeared only after several years of follow-up. In contrast, the effect of adding 3TC to AZT-containing regimens was statistically significant after only one year, halving mortality and the incidence of new AIDS-defining opportunistic infection. Adding ritonavir had a similar effect after 20 week's follow-up in far-advanced HIV infection. The most potent regimens combine AZT, 3TC, and either ritonavir or indinavir; in the majority of patients thus treated viremia became undetectable (< 500 copies/ml).

Acquired Immunodeficiency Syndrome↗
PubMed1997

Human immunodeficiency virus type 1 protease inhibitors.

Until recently, treatment for human immunodeficiency virus type 1 (HIV-1) infection was limited to the use of nucleoside inhibitors of the viral enzyme reverse transcriptase. While these agents initially offered promise, they have only modest antiviral activity and the benefits of treatment are limited by the emergence of drug resistance and dose-limiting toxic effects. Development of more potent drugs that target different stages of the virus life cycle has thus been aggressively pursued. Efforts to develop inhibitors of HIV-1 protease have yielded a potent new class of compounds that suppress HIV-1 replication to an extent far greater than was previously attainable. Four protease inhibitors, saquinavir mesylate, ritonavir, nelfinavir, and indinavir sulfate, have been approved by the Food and Drug Administration. Other agents are undergoing active investigation. The purpose of this article is to review the currently available data on those agents that have been approved for clinical use.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Kaposi's-sarcoma-associated herpesvirus is detected in peripheral blood mononuclear cells of HIV-infected homosexuals more often than in heterosexuals.

PURPOSE: The Kaposi's-sarcoma-associated herpesvirus is thought likely to play an important part in the pathogenesis of Kaposi's sarcoma, which is the most common tumor in AIDS patients. To determine whether peripheral blood is also infected by the virus, we prospectively tested mononuclear cells from HIV-infected individuals, both with and without Kaposi's sarcoma. PATIENTS AND METHODS: Thirty-three patients with AIDS were studied. Twenty-three were homosexuals, and 10 of these patients had Kaposi's sarcoma. All 10 nonhomosexual patients were free of Kaposi's sarcoma. PCR amplification of peripheral blood mononuclear cells was performed for a 233-base-pair segment of Kaposi's-sarcoma-associated herpesvirus on all patients. Fisher's exact test was used to compare the patient groups. RESULTS: Kaposi's-sarcoma-associated herpesvirus sequences were detected in the peripheral blood mononuclear cells of homosexual men both with (7/10) and without (5/13) Kaposi's sarcoma. However, none of the nonhomosexual patients (0/10) had detectable virus. Therefore, those with Kaposi's sarcoma are at greater risk for Kaposi's-sarcoma-associated herpesvirus infection than patients without Kaposi's sarcoma, and among HIV-positive patients without Kaposi's sarcoma, homosexuals are more likely to have detectable Kaposi's-sarcoma-associated herpesvirus than are nonhomosexuals. In the homosexual patients, the presence of virus was unrelated to total CD4+ cell counts. A comparative dilutional analysis showed that the nonhomosexual patients had a low viral load in their peripheral blood mononuclear cells relative to most homosexuals with Kaposi's sarcoma. Sequential studies on two patients revealed clearing of the virus while on therapy; one patient was treated for HIV with the protease inhibitor indinavir, and the other patient was treated for Kaposi's sarcoma with liposomal doxorubicin. CONCLUSIONS: These results indicate that Kaposi's-sarcoma-associated herpesvirus is harbored in peripheral blood mononuclear cells of HIV-infected patients, and that the rates of infection are significantly higher in homosexual men compared with their nonhomosexual counterparts. The significance of viral clearing in response to therapy is unknown but warrants further study, as prophylactic treatment for this virus might alter the occurrence of Kaposi's sarcoma in this susceptible patient population.

AIDS-Related Opportunistic Infections↗