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G J Weverling

Publications and source records attributed to G J Weverling.

At least 37 records · Page 2Linked to original sources
PubMed2001

Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection.

BACKGROUND: Changes in body fat distribution are an adverse effect of therapy with HIV protease inhibitors (PI). It has been suggested that nucleoside analogue reverse transcriptase inhibitors (NRTI) may also contribute to this so-called lipodystrophy syndrome, but the relative contribution of the two drug classes is unclear as they are usually administered concomitantly. METHOD: The occurrence of lipodystrophy, as reported by physicians using no standardized criteria, was followed in patients randomly assigned to treatment with either a PI alone or a PI combined with an NRTI. The patients were part of a multicenter, open-label, randomized comparison of ritonavir (RTV)/saquinavir (SQV) with or without the addition of stavudine (d4T) in HIV-1-infected patients without prior PI and d4T experience (the Prometheus study). RESULTS: Lipodystrophy was reported in 29 of 175 (17%) patients during 96 weeks of follow up. Overall, it was reported significantly more frequently in patients who were randomized to RTV/SQV/d4T (22/88; 25%), than in patients randomized to RTV/SQV alone (7/87; 8%) (P = 0.003). When the analysis was limited to patients without any prior antiretroviral experience, lipodystrophy likewise was significantly more frequent in patients randomized to RTV/SQV/d4T (12/50; 24%) than in those randomized to RTV/SQV (2/44; 5%) (P = 0.008). CONCLUSION: This randomized clinical trial, in spite of not having been blinded, supports a contributory role of NRTI in the development of antiretroviral therapy-associated lipodystrophy. The low incidence of lipodystrophy in patients with no or limited NRTI exposure supports further evaluation of NRTI-sparing regimens as alternatives to current antiretroviral regimens.

Anti-HIV Agents↗
PubMed2001

Sexual risk behaviour relates to the virological and immunological improvements during highly active antiretroviral therapy in HIV-1 infection.

OBJECTIVES: To evaluate the effect of highly active antiretroviral therapy (HAART) on the sexual behaviour of homosexual men, we conducted (i) an ecological study of time trends in sexual behaviour and sexually transmitted diseases; (ii) a HAART-effect study focused on the practice of unprotected anogenital sex. DESIGN: Subjects were participants in the ongoing Amsterdam Cohort Studies (ACS) among homosexual men, initiated in 1984. Data for (i) represented all ACS visits by HIV-1-positive and -negative participants who entered ACS at or below 30 years of age and were followed until 35 years (n = 1062). Data for (ii) represented all ACS visits of HIV-1-positive men from 1992 to 2000 (n = 365), of whom 84 were HAART recipients with at least 2 months of behavioural follow-up. RESULTS: (i) After HAART became generally available in July 1996, unprotected sex was practised more frequently and the incidence of gonorrhoea was higher compared to March 1992-June 1996 among HIV-1-negative and -positive men, respectively. (ii) Among HIV-1-positive men, a higher level of unprotected sex with casual partners was observed after HIV-1 RNA became undetectable and CD4 cell counts increased with the use of HAART. Notably, in individuals who did not receive HAART, high HIV-1-RNA levels (above 10(5) copies/ml) were likewise related to unprotected sex with casual partners. CONCLUSION: Data support the need for the reinforcement of safe sex prevention messages among HIV-1-negative men, and our data also provide a lead for redirecting and tailoring current prevention strategies to the needs of HIV-1-positive men.

Adult↗
PubMed2001

Durable HIV-1 suppression with indinavir after failing lamivudine-containing double nucleoside therapy: a randomized controlled trial.

OBJECTIVE: To assess the durability of the antiretroviral effect in plasma and cerebrospinal fluid (CSF) of antiviral therapy intensification, produced by the addition of indinavir from week 12 onwards to the original regimen of zidovudine/lamivudine or stavudine/lamivudine, after 72 weeks of follow-up using an ultrasensitive HIV-1 RNA assay. To assess CSF concentrations of indinavir at week 48. DESIGN: In a prospectively, randomized, open, single-centre study, antiretroviral-naive patients (CD4 cell count > or =200 cells/microl and a plasma HIV-1 RNA level 10,000 copies/ml) were assigned to a combination of zidovudine/lamivudine or stavudine/lamivudine. Indinavir could be added to the double nucleoside analogue regimen from week 12 or thereafter in case the plasma HIV RNA level was insufficiently suppressed (>500 copies/ml). RESULTS: Forty-seven patients were enrolled (23 stavudine/lamivudine and 24 zidovudine/lamivudine), of whom 33 completed a follow-up of 72 weeks. Indinavir was added in 89% (42/47) of the patients. Only one discontinuation occurred due to virological failure. At week 72, the median plasma HIV-1 RNA levels in the zidovudine/lamivudine group had decreased from 4.80 log10 copies/ml to <500 copies/ml in 100% of patients and <50 copies/ml in 86.6% of the patients. In the stavudine/lamivudine group the plasma HIV-1 RNA decreased from 4.98 log10 copies/ml at baseline to <500 copies/ml in 100% of patients and <50 copies/ml in 66.7% of the patients. On an intent-to-treat basis these figures were 54.2 and 52.2% for zidovudine/lamivudine and stavudine/lamivudine, respectively, for the 50 copies/ml assay. The median CD4 cell count increased from 315 cells/microl, with 150 cells/microl in the zidovudine/lamivudine arm, and from 290 cells/microl, with 310 cells/microl in the stavudine/lamivudine arm (P=0.0001). However, the percentage of CD4 cells did not differ in each group. In the zidovudine/lamivudine group 9/10 and 5/5, and in the stavudine/lamivudine group 11/11 and 6/6 had a CSF HIV-1 RNA level <50 copies/ml at week 12 and 48, respectively. The CSF indinavir concentration ranged from 50 to 170 ng/ml. CONCLUSION: The long-term HIV-1 suppression observed in this study is remarkable, as adding a single antiretroviral agent to a failing regimen goes against current notions of adequate therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection.

OBJECTIVE: To investigate the risk of hepatotoxicity after initiation of protease inhibitor-containing highly active antiretroviral therapy (HAART) for HIV-1 infected patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) co-infection. DESIGN: Retrospective study with 394 HIV-1-infected patients initiating HAART at a single university clinic. METHODS: Liver enzyme elevation (LEE) was defined as alanine aminotransferase or aspartate aminotransferase at least five times the upper limit of normal and an absolute increase of > 100 U/l. Relative risks for time to LEE were estimated using Cox proportional hazards models. RESULTS: Of 394 patients 7% were hepatitis B surface antigen (HBsAg)-positive and 14% were anti-HCV-positive. Patients with chronic hepatitis had a higher risk for LEE compared with patients without co-infection: 37% versus 12% respectively. After adjustment for higher baseline transaminases, the presence of HBsAg or anti-HCV remained associated with an increased risk of LEE - relative risk 2.78 (95% confidence interval, 1.50-5.16) and 2.46 (95% confidence interval, 1.43-4.24) respectively. In patients with LEE, transaminases declined whether HAART was continued or modified. Of patients with chronic HBV infection 38% lost HBeAg or developed anti-HBe after initiation of HAART, and one seroconverted from HBsAg-positive to anti-HBs-positive. However, there was no clear relationship with LEE. CONCLUSIONS: HIV-1-infected patients co-infected with HBV or HCV were at considerably higher risk of developing LEE when HAART was initiated compared with patients without co-infection, but it is usually not necessary to modify antiretroviral therapy.

Adult↗
PubMed2000

Risk factors for hepatotoxicity in HIV-1-infected patients receiving ritonavir and saquinavir with or without stavudine. Prometheus Study Group.

Liver enzyme elevation (LEE) is commonly observed after combination antiretroviral therapy (ARVT) for HIV infection is begun. Potential risk factors for LEE after treatment with ritonavir and saquinavir with or without stavudine were investigated in 208 HIV-infected patients, by use of the Cox proportional hazard model. Eighteen patients (9%) developed LEE during the 48-week follow-up. Multivariate analysis, adjusted for baseline levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), showed that hepatitis B surface antigen (HBsAg) positivity (relative risk [RR], 8.8; 95% confidence interval [CI], 3.3-23.1) and the use of stavudine (RR, 4.9; 95% CI, 1.5-16.0) were the only significant risk factors for developing LEE. After LEE occurred, ALT and AST concentrations decreased by >50% in 13 of 14 patients who continued ARVT during LEE. In this study, it appeared safe to continue ARVT during LEE; however, more data from larger studies are required to confirm this finding.

Adult↗
PubMed2000

A randomized, dose-finding study with didanosine plus stavudine versus didanosine alone in antiviral-naive, HIV-infected Thai patients.

OBJECTIVES: To evaluate the safety and efficacy of four different regimens of didanosine (ddI) + stavudine (d4T) in HIV-infected Thais. DESIGN: Prospective, open-label, randomized study. METHODS: Patients were randomized to four regimens of high and low doses of ddI and d4T or to ddI alone. D4T was added to the ddI-alone arm after week 24. The duration of study was 48 weeks. RESULTS: Seventy-eight patients were randomized (mean CD4 cell count, 255 x 10(6)/l; mean plasma HIV-1 RNA; 4.3 log10 copies/ml). In the intent-to-treat analysis, 78% of patients in the pooled combination arms and 20% of the patients in the ddI alone arm (to which d4T was added after 24 weeks) showed plasma HIV-1 RNA < 500 copies/ml at week 24 (P < 0.001), and 59% versus 53% at week 48, respectively. In addition, the proportion of patients with < 50 HIV-1 RNA copies/ml was 13% versus 7% at week 24 (P = 0.5) and 17% versus 20% at week 48 respectively. At week 24, median CD4 cell count increases from baseline were 101 x 10(6)/l in the pooled combination versus 76 x 10(6)/l in the ddI alone arm (P = 0.78). Logistic regression modeling suggested a correlation between receiving high dose ddI and achieving HIV-1 RNA < 500 copies/ml at week 48 (P = 0.07). CONCLUSIONS: The d4T/ddI combination was superior to ddI alone in producing HIV-1 viral suppression. At week 48, > 60% of patients treated with this combination reached HIV-1 RNA levels < 500 copies/ml. Receiving high dose ddI but not d4T may correlate with a better viral suppression.

Anti-HIV Agents↗
PubMed2000

Enhanced penetration of indinavir in cerebrospinal fluid and semen after the addition of low-dose ritonavir.

OBJECTIVE: Penetration of antiretroviral drugs into anatomical HIV-1 reservoirs such as the male genital tract and the central nervous system is important. Data on indinavir (IDV) concentrations in seminal plasma are lacking and IDV concentrations in cerebrospinal fluid are at best borderline. DESIGN: Thirteen patients were treated with zidovudine (or stavudine), lamivudine, abacavir, nevirapine and IDV (1000 mg three times daily). When nevirapine led to low IDV concentrations, IDV was changed into the combination IDV/ritonavir (RTV) 800/100 mg twice daily to improve the pharmacokinetic profile of IDV. METHODS: A serum pharmacokinetic profile, a semen sample and a cerebrospinal fluid sample were collected at weeks 8, 24, 48 and 72. RESULTS: Addition of RTV increased the median IDV trough concentration in serum from 65 to 336 ng/ml (P = 0.005). Median IDV concentration in seminal plasma increased from 141 to 1634 ng/ml (P = 0.002) (n = 9) and in cerebrospinal fluid from 39 (n = 12) to 104 (n = 7) ng/ml (P < 0.001). In six patients with samples collected both before and after the addition of RTV, the IDV concentration in seminal plasma increased 8.2 times [95% confidence interval (CI) 5.2-11.6], and in cerebrospinal fluid 2.4 times (95% CI 1.8-3.9). CONCLUSIONS: IDV penetrates well into the male genital tract. The addition of low-dose RTV not only increases IDV concentrations in serum but also in seminal plasma and cerebrospinal fluid, thereby probably improving the potency of the regimen in these anatomical HIV reservoirs. Higher serum trough levels alone can not sufficiently explain the observed increases in seminal plasma and cerebrospinal fluid concentrations. Inhibition of P-glycoprotein-mediated transport by RTV might be an additional mechanism.

Adult↗
PubMed2000

Human herpesvirus 8 infections in the Amsterdam Cohort Studies (1984-1997): analysis of seroconversions to ORF65 and ORF73.

We have shown previously that human herpesvirus 8 (HHV8) seroconversion for antibodies to the latency-associated nuclear antigen encoded by ORF73 and/or the lytic capsid antigen (vp19) encoded by ORF65 is associated with orogenital contact and is strongly linked to the development of Kaposi's sarcoma among HIV-infected individuals in the Amsterdam Cohort Studies. Here, we investigate the relationship between seroconversion to these antigens and primary HHV8 infection. Between 1984 and 1997, 215 HHV8 seroconversions to ORF73 (106 cases or 49%) and/or to ORF65 (159 cases or 74%) were recorded in the cohort of homosexual men. The HHV8 seroconversion rate among HIV-infected homosexual men (6.2 per 100 person years) was consistently higher than among HIV-uninfected men (2.6 per 100 person years). In HIV-infected but not in uninfected individuals, seroconversion to ORF73/latency-associated nuclear antigen precedes that to ORF65/vp19. Antibody levels to both ORF65- and ORF73-encoded antigens were higher in HIV-infected than in HIV-uninfected men, and among HIV-seropositives, antibody levels to ORF65/vp19 rise even higher with declining CD4 cell counts and peak with Kaposi's sarcoma development, suggesting continuing and increasing viral replication. In 10.3% of HHV8 seroconversions, transient serum viremia could be demonstrated before or at seroconversion. Together with the previously reported link between unprotected orogenital sex and HHV8 seroconversion, our observations suggest that HHV8 seroconversions result from primary infections.

Antibodies, Viral↗
PubMed2000

Risk factors for human herpesvirus 8 seropositivity and seroconversion in a cohort of homosexual men.

Sexual and nonsexual modes of transmission of human herpesvirus 8 (HHV8) have been suggested, but specific routes remain unclear. Therefore, the objective of this study was to assess risk factors for HHV8 seropositivity and determine specific sexual practices associated with HHV8 seroconversion. Sera from 1,458 homosexual men (Amsterdam Cohort Study, 1984-1996) were tested for antibodies to HHV8 with a modified version of an enzyme immunoassay, using recombinant HHV8 lytic phase capsid (ORF65) and latent phase nuclear (ORF73) proteins. HHV8 seroprevalence at study entry was 20.9% (305/1,458); was highest among those with positive human immunodeficiency virus (HIV) status, no steady partner, and southern European or Latin American nationality; and increased with older age and higher number of sexual partners. During follow-up, 215 men seroconverted for HHV8 (incidence: 3.6/100 person-years). Both prevalence and incidence rates remained more or less stable during the study period. Orogenital insertive sex (odds ratio (OR) = 5.95; 95% confidence interval (CI): 2.88, 12.29) or orogenital receptive sex (OR = 4.29; 95% CI: 2.11, 8.71) with more than five partners in the past 6 months, older age (OR = 2.89; 95% CI: 1.13, 7.34, when older than 45 years), and preceding HIV infection (OR = 2.47; 95% CI: 1.53, 3.99) were independent predictors for HHV8 seroconversion. The authors found strong evidence for orogenital transmission of HHV8 among homosexual men.

Adult↗
PubMed2000

Cerebrospinal fluid beta2-microglobulin, monocyte chemotactic protein-1, and soluble tumour necrosis factor alpha receptors before and after treatment with lamivudine plus zidovudine or stavudine.

CSF levels of beta2-microglobulin (b2m), monocyte chemotactic protein-1 (MCP-1), soluble tumor necrosis factor receptors (sTNFRs), and HIV-1 RNA were determined in 16 neurologically asymptomatic HIV-1 infected patients before and 12 weeks after treatment with lamivudine plus zidovudine or stavudine. b2m levels were significantly higher in patients (1.7 mg/l) compared with controls (0.8 mg/l) (P < 0.001), and decreased to 1.1 mg/l during treatment (P = 0.001). MCP-1 levels were low, and did not change during treatment. Levels of sTNFR type I were elevated in patients (0.92 ng/ml) compared to controls (0.30 ng/ml) (P = 0.03), but did not change during treatment. Levels of sTNFR type II were below the limit of detection in most patients and controls. In conclusion, CSF levels of b2m and HIV-I RNA, but not sTNFRs or MCP-1, are candidate surrogate markers of treatment efficacy in early CNS infection.

Adult↗
PubMed2000

Toxicity and drug exposure in a quadruple drug regimen in HIV-1 infected patients participating in the ADAM study.

OBJECTIVE: To study the relationship between toxicity and the exposure to nelfinavir and saquinavir as part of a quadruple drug regimen. DESIGN: The ADAM study is a randomized study to investigate the feasibility of induction-maintenance therapy in HIV-1 infection. METHODS: HIV-1-infected patients with no prior use of antiretroviral treatment started induction therapy consisting of stavudine + lamivudine + nelfinavir + saquinavir for a period of 26 weeks. Data regarding toxicity of the quadruple regimen and exposure to the protease inhibitors were collected. RESULTS: Seven of the 65 patients enrolled had to switch therapy for reasons of toxicity within the first 26 weeks. Diarrhoea was frequently reported (49 of 65, one discontinuation), but could be relieved by using antidiarrhoeal agents. Laboratory monitoring revealed elevated liver enzymes (leading to four discontinuations) and mild to moderate elevations of triglycerides and cholesterol (nine and 23 of 65, respectively). The exposure to saquinavir and nelfinavir was lower than expected. Abdominal pain was associated with a higher exposure to nelfinavir or saquinavir. The association of nausea and abdominal distension with drug exposure appeared to vary over time. CONCLUSIONS: The quadruple drug regimen was quite well tolerated. Diarrhoea was frequently reported but could be relieved by the use of antidiarrhoeal agents. In comparison with other protease inhibitor combinations, lipid abnormalities in plasma were infrequent and mild. With the exception of diarrhoea, all gastrointestinal complaints observed were found to be associated with the level of exposure to nelfinavir or saquinavir. The exposure to the protease inhibitors was relatively low, although the virologic efficacy of the regimen used was satisfactory.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Prognostic value of cytokine concentrations (tumor necrosis factor-alpha, interleukin-6, and interleukin-10) and clinical parameters in severe melioidosis.

Raised serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-10 are associated with mortality in patients with sepsis, but it is not known whether elevated cytokine levels are independently predictive of mortality. Cytokine assays (TNF-alpha, IL-6, and IL-10) were performed on admission plasma samples from 172 adult Thai patients with severe melioidosis. Mortality was 31.4%. APACHE II score; septicemia; plasma lactate; TNF-alpha, IL-6, and IL-10 concentrations; and IL-10/TNF-alpha and IL-6/IL-10 ratios were each associated with outcome (P</=.001 for all variables). Only the APACHE II score and either IL-6 or IL-10 concentration were independent predictors of mortality, as determined by use of multiple logistic regression (with cytokine concentrations and ratios entered separately). In a multivariate analysis, including both IL-6 and IL-10, the IL-10 concentration was no longer predictive. Therefore, APACHE II scores and either IL-6 or IL-10 concentration may be the most reliable parameters for stratification of patients in future studies of severe gram-negative sepsis.

APACHE↗
PubMed2000

Value of different assays for detection of human cytomegalovirus (HCMV) in predicting the development of HCMV disease in human immunodeficiency virus-infected patients.

In the present prospective study, five blood tests for detection of human cytomegalovirus (HCMV), nucleic acid sequence-based amplification (NASBA) for detection of early (immediate-early antigen) and late (pp67) mRNA, PCR for detection of HCMV DNA (DNA PCR), culture, and pp65 antigenemia assay, and culture and DNA PCR of urine and throat swab specimens were compared for their abilities to predict the development of disease caused by HCMV (HCMV disease). Of 101 human immunodeficiency virus (HIV)-infected patients with </=100 CD4(+) lymphocytes per mm(3), 25 patients developed HCMV disease. The pp65 antigenemia assay (sensitivity, 50%; specificity, 89%) and DNA PCR of blood (sensitivity, 69%; specificity, 75%) were most accurate in predicting the development of HCMV disease within the next 12 months. Both blood culture and late pp67 mRNA NASBA had high specificities (91 and 90%, respectively) but low sensitivities (25 and 13%, respectively). The sensitivities of urine culture, DNA PCR, throat swab specimen culture, DNA PCR, and NASBA of blood for detection of the immediate-early antigen were 73, 87, 53, 67, and 63%, respectively, and the specificities were 58, 46, 76, 60, and 72%, respectively. The positive predictive values of all tests however, were low and did not exceed 50%. In conclusion, virological screening by these qualitative assays for detection of HCMV is of limited value for prediction of the development of HCMV disease in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Quantitative pp65-antigenemia assay for the prediction of human cytomegalovirus disease in HIV-infected patients.

OBJECTIVE: To evaluate the ability of a quantified pp65-antigenemia assay to predict the development of human cytomegalovirus (HCMV) disease in patients with an advanced HIV infection. DESIGN: A prospective longitudinal study between March 1993 and December 1996. Blood samples for the pp65-antigenemia assay were drawn at 2-3 month intervals. SETTING: AIDS department of an institutional tertiary care centre. PATIENTS: A total of 101 HIV-infected patients with CD4 lymphocyte counts of 100/mm3 or less were enrolled. Ninety-seven patients were eligible for analysis. All patients gave informed consent. MAIN OUTCOME MEASURES: The development of HCMV disease. RESULTS: Of the 97 patients, 24 developed HCMV disease after a median follow-up of 10.6 months. Three months before the development of HCMV disease, an increase in the median number of pp65-antigen-positive leukocytes was observed. The highest combination of sensitivity (45%) and specificity (94%) for the development of HCMV disease within the next 3 months was found when an assay cut-off level of 48/10(5) pp65-antigen-positive leukocytes was applied, with a positive predictive value (PPV) for the development of HCMV disease of 75%. The Kaplan-Meier estimate of HCMV disease-free survival after patients reached 48/10(5) or more antigen-positive leukocytes on longitudinal follow-up was a median 3.7 months [95% confidence interval (CI), 2.5-8.5]. The hazard ratio (HR) of this threshold level for the development of HCMV disease was 9.6 (95% CI, 4.2-21.8). CONCLUSION: Longitudinal follow-up using the pp65-antigenemia assay of HIV-infected patients with a low CD4 lymphocyte count improves the identification of patients who will develop HCMV disease in the foreseeable future, and should be considered for the selection of patients who may benefit from pre-emptive HCMV treatment.

Adult↗
PubMed1999

Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. EuroSIDA Study Group.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved rates of CD4-lymphocyte recovery and decreased the incidence of HIV-1-related morbidity and mortality. We assessed whether prophylaxis against Pneumocystis carinii pneumonia (PCP) can be safely discontinued after HAART is started. METHODS: We investigated 7333 HIV-1-infected patients already enrolled in EuroSIDA, a continuing prospective observational cohort study in 52 centres across Europe and Israel. We did a person-years analysis of the rate of discontinuation of PCP prophylaxis and of the incidence of PCP after the introduction of HAART into clinical practice from July, 1996. FINDINGS: The rate of discontinuation of primary and secondary PCP prophylaxis increased up to 21.9 discontinuations per 100 person-years of follow-up after March, 1998. 378 patients discontinued primary (319) or secondary (59) prophylaxis a median of 10 months after starting HAART. At discontinuation for primary and secondary prophylaxis, respectively, the median CD4-lymphocyte counts were 274 cells/microL and 270 cells/microL, the median plasma HIV-1 RNA load 500 copies/mL, and the median lowest recorded CD4-lymphocyte counts 123 cells/microL and 60 cells/microL. During 247 person-years of follow-up, no patient developed PCP (incidence density 0 [95% CI 0-1.5]). INTERPRETATION: The risk of PCP after stopping primary prophylaxis, especially in patients on HAART with a rise in CD4-lymphocyte count to more than 200 cells/microL, is sufficiently low to warrant discontinuation of primary PCP prophylaxis. Longer follow-up is needed to confirm a similarly low risk for stopping secondary PCP prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human immunodeficiency virus type 1-infected persons.

The outcome and predictors of virologic treatment failure of highly active antiretroviral therapy (HAART) were determined for 271 human immunodeficiency virus (HIV)-infected protease inhibitor-naive persons. During a follow-up of 48 weeks after the initiation of HAART, 6.3% of patients experienced at least one new AIDS-defining event, and 3.0% died. Virologic treatment failure occurred in 40% (indinavir, 27%; ritonavir, 30%; saquinavir, 59%; ritonavir plus saquinavir, 32%; chi2, P=.001). Risk factors for treatment failure were baseline plasma HIV-1 RNA (odds ratio [OR], 1.70 per log10 copies increase in plasma HIV-1 RNA), baseline CD4 cell count (OR, 1. 35 per 100 CD4 cells/mm3 decrease), and use of saquinavir versus other protease inhibitors (OR, 3.21). During the first year of treatment, 53% of all patients changed (part of) their original HAART regimen at least once. This was significantly more frequent for regimens containing saquinavir (62%; 27% for virologic failure) or ritonavir (64%; 55% for intolerance) as single protease inhibitor.

Acquired Immunodeficiency Syndrome↗