Biomedical subjects

P Vernazza

Publications and source records attributed to P Vernazza.

At least 19 recordsLinked to original sources

PubMed2005

Adherence to antiretroviral therapy and its impact on clinical outcome in HIV-infected patients.

We analyse data on patient adherence to prescribed regimens and surrogate markers of clinical outcome for 168 human immunodeficiency virus infected patients treated with antiretroviral therapy. Data on patient adherence consisted of dose-timing measurements collected for an average of 12 months per patient via electronic monitoring of bottle opening events. We first discuss how such data can be presented to highlight suboptimal adherence patterns and between-patient differences, before introducing two novel methods by which such data can be statistically modelled. Correlations between adherence and subsequent measures of viral load and CD4+T-cell counts are then evaluated. We show that summary measures of short-term adherence, which incorporate pharmacokinetic and pharmacodynamic data on the monitored regimen, predict suboptimal trends in viral load and CD4+T-cell counts better than measures based on adherence data alone.

Antiretroviral Therapy, Highly Active↗

PubMed2005

Interferon alpha-2a plus ribavirin 1,000/1,200 mg versus interferon alpha-2a plus ribavirin 600 mg for chronic hepatitis C infection in patients on opiate maintenance treatment: an open-label randomized multicenter trial.

BACKGROUND: Many intravenous opiate users are infected with hepatitis C virus (HCV) but few are treated. Although this complies with various guidelines, virtually no published evidence supports such a recommendation. PATIENTS AND METHODS: In a multicenter study, HCV-infected patients in opiate maintenance treatment programs received interferon plus high- or low-dose ribavirin (1,000/1,200 mg or 600 mg). HIV-coinfected patients were not included. Endpoints were feasibility, efficacy, side effects, and reasons for dropout. RESULTS: Of the 420 patients who tested positive for HCV, 27 (6%) were enrolled; 393 (94%) either failed to meet the inclusion criteria or refused treatment. Virologic end-of-treatment response was achieved in 12/27 patients, and sustained response in 13/27 (48%). Response depended on viral genotype, not ribavirin dose. The two doses of ribavirin did not differ in their side effects. CONCLUSION: In a small fraction of HCV-infected intravenous drug users in an opiate maintenance treatment program, antiviral therapy was feasible, safe, and effective. The success rate was comparable to that achieved in controlled studies that excluded drug users.

Antiviral Agents↗

PubMed2005

Starting or changing therapy - a prospective study exploring antiretroviral decision-making.

BACKGROUND: When to start or change antiretroviral treatment against HIV infection is of major importance. Patients' readiness is considered a major factor influencing such treatment decisions, in particular because no objective, absolute time point when to start antiretroviral therapy exists. We aimed at evaluating patients' readiness to start or change antiretroviral therapy (ART). PATIENTS AND METHODS: HIV-infected patients starting or changing ART between July 2002 and February 2003, treating physicians and nurses participated in this prospective, observational multicenter study. We assessed shared decision-making including qualitative aspects, expected treatment decisions and treatment status after 3 months. RESULTS: 75 patients were included. Of 34 patients for whom starting ART was considered, 27 (79%) indicated that they were willing to start treatment. After 3 months, 21 of 27 (78%) actually started therapy, six did not. Patients with depression were less likely to be ready for ART (p < 0.05). Of 41 patients for whom changing ART was considered, 35 (85%) indicated that they were willing to change treatment. Of the latter 35 patients, 33 (94%) finally changed ART within 3 months. Physicians and nurses were too optimistic in predicting the start or change of ART. The main reason to start or change ART was the sole recommendation of the physician (52% in those starting, 61% in those changing ART). Patients mainly judged the decision as shared and were very satisfied (71%) with the process. Qualitative findings revealed the importance of a dialectic decisionmaking, described with two categories: "dealing with oneself and others"' and "understanding and being understood." CONCLUSION: Patients mainly shared the decision made during consultation. Although physicians have an essential role concerning ART, patients, physicians, and nurses all contribute to the decision. Qualitative findings indicate the importance for health-care providers to include patients' expertise and contributions.

Adult↗

PubMed2004

[Adherence and resistance].

With the introduction of highly efficacious HAART therapy for HIV/AIDS successful long-term therapy became available. Nevertheless, it also revealed the fragile nature of antiretroviral therapy: resistant virus variants emerged, sometimes already after only short treatment episodes. And they soon began decreasing the newly gained armamentarium of specific inhibitors for HIV. A primary cause for failure could be found in a poor adherence to therapy or in the insufficient metabolic availability of a drug. It is primarily this fact that allows the HI-virus, although delayed, to complete its life cycle and to adapt to those incompletely controlling drug levels. And finally the conditioned virus will fail to respond to the respective drug. For the clinical therapy concept it can be fatal if a resistance development remains undetected. At this point the recently established diagnostic tool of resistance-determination is gaining importance: it allows detection and characterization of viral resistances early after emergence, helping to adapt and optimize HAART therapy. Two distinct methodologies have been developed: Genotyping and viral Phenotyping. Genotyping is technically less demanding and can principally be performed within one week. It is based on the identification of (known) resistance-associated mutations and on their combination onto one "virtual viral genome". This can be compared with known resistance-patterns and allows then the extrapolation of a viral resistance. The more demanding phenotyping method represents a direct determination, utilizing the concept of an "in vitro therapy": every drug to be assessed will be directly tested against virus information from the respective patient. As a consequence phenotyping has, particularly in its special format of a "replicative phenotyping", special utility for mixed virus populations or emerging minorities in the same patient, for viruses with new (unknown) mutations, and for viruses with reduced replicative capacity. Either method for the determination of HIV resistance reflects still a relatively young diagnostic tool. As a consequence current studies, underway in Switzerland and supported by the SHCS, aim at the further optimization of the tests and at an evaluation of their long term therapeutic benefit.

Anti-HIV Agents↗

PubMed2003

Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial.

BACKGROUND: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration. METHODS: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm. RESULTS: Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline. CONCLUSIONS: The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.

Anti-HIV Agents↗

PubMed2002

Prospective epidemiologic survey of patients with community-acquired pneumonia requiring hospitalization in Switzerland.

BACKGROUND: Community-acquired pneumonia (CAP) is a common problem and the principal infection requiring hospitalization, but its treatment is complicated by the difficulty in microbiological diagnosis and the increasing incidence of antibiotic resistance among respiratory pathogens. The purpose of this paper is to present the main epidemiologic features of patients with CAP requiring hospitalization in our country. METHODS: We enrolled three hundred and eighteen adult patients with CAP requiring hospitalization in seven large medical centers in Switzerland during two winter periods. The patients' mean age was 70.4 years. This study describes the epidemiology of these patients. Clinical, radiologic and microbiological evaluations were performed at study entry during treatment, and at 4 weeks post-therapy. For microbiological diagnostic purposes, sputum culture, throat swab culture, PCR, blood cultures, Legionella urinary antigen and serologic evaluations were also performed. RESULTS: Despite the higher mean age, the overall mortality rate was 8%, lower than in other comparable studies. The most common underlying diseases present at study entry were cardiac failure (23%), chronic obstructive pulmonary disease (20%), renal failure (15%), and diabetes (12%); 40% of the patients were smokers. Although dyspnea, cough and positive pulmonary auscultation findings were present in about 90% of patients, fever >38 degrees C was present in only 64%. The most frequently isolated respiratory pathogens were Streptococcus pneumoniae (12.6%), Haemophilus influenzae (6%), Staphylococcus aureus (1.6%), and Moraxella catarrhalis (1.6%). Atypical pathogens were frequently found, with the following distribution: Mycoplasma pneumoniae, 7.5%; Chlamydia pneumoniae, 5.3%; and Legionella pneumophila, 4.4%. The mean duration between onset of symptoms and hospital admission was 4.8 days, and the mean treatment duration was 12.1 days. Two weeks after the start of therapy, although clinical symptoms were absent, radiologic infiltrates were still present in 24% of patients. CONCLUSIONS: The microbiological diagnosis in CAP can be established in only about 50% of cases with the combination of several diagnostic tools. Epidemiologic surveys of CAP should be performed on a regular basis, regionally, as a way to improve the management of these infections.

Aged↗

PubMed2002

Ritonavir plus saquinavir versus single protease inhibitor therapy in protease inhibitor-naive HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: To compare the response to ritonavir (RTV) plus saquinavir (SQV) with single protease inhibitor (PI) therapies among PI-naive HIV-1 infected individuals. METHODS: Response to treatment was analysed according to the intent-to-treat principle in a prospective observational cohort study of 177 patients who between May 1995 and March 2000 started a double PI therapy with RTV and SQV (nonboosting dosages) plus at least one nucleoside reverse transcriptase inhibitor (NRTI) and 2,214 patients with a single PI therapy plus two NRTIs. We used survival analysis and Cox's proportional hazard regression methods. The primary endpoint was the time to a plasma viral load of < 400 copies/mL. Secondary endpoints were taken as a gain in the CD4 count of >100 cells/microL, and change of initial PI for any reason. RESULTS: Baseline characteristics in both treatment groups were balanced. Median follow-up in both groups was 10.4 months. Time to an HIV-1 viral load of < 400 copies/mL and an increase in the CD4 count of >100 x 10(6) cells/L was shorter for RTV plus SQV compared with single PI regimens (log rank test for each endpoint P < 0.05). The adjusted hazard ratios of RTV plus SQV compared with single PI regimens were 1.21 (95% confidence interval 0.99-1.47) for achieving an HIV-1 viral load of < 400 copies/mL, 1.12 (0.88-1.42) for an increase in the CD4 count of > 100 cells/microL, and 0.90 (0.73-1.11) for change of first PI regimen. CONCLUSIONS: Treatment with RTV plus SQV compared with single PI regimens appeared to give similar results for virological or immunological response.

Adolescent↗

PubMed2001

HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load.

CONTEXT: It is unclear whether delay in initiation of antiretroviral therapy (ART) may lead to a poorer viral load response for patients with human immunodeficiency virus (HIV). OBJECTIVE: To characterize the relationship of viral load response to ART with baseline CD4 cell count and baseline viral load. DESIGN: Inception cohort of 3430 therapy-naive patients with HIV, of whom 3226 patients had at least 1 viral load count after the start of ART. SETTING: Three cohort studies of patients cared for in HIV clinics in Europe between 1996 and 2000. PATIENTS: All patients initiating ART consisting of at least 3 drugs initiated in or after 1996 and for whom CD4 cell count and viral load were available in the prior 6 months (at most). MAIN OUTCOME MEASURES: Viral load decrease to below 500 copies/mL; viral load rebound to above 500 copies/mL (2 consecutive values). RESULTS: Of 3226 patients during the median follow-up of 119 weeks, 2741 (85%) experienced viral suppression to less than 500 copies/mL by 32 weeks. Relative hazards (RHs) of achieving this were 1.08 (95% confidence interval [CI], 0.98-1.21) and 0.94 (95% CI, 0.84-1.04) for baseline CD4 cell counts between 200 and 349 x 10(6)/L and baseline CD4 cell counts lower than 200 x 10(6)/L, respectively, compared with baseline CD4 cell counts of 350 x 10(6)/L or higher, after adjustment for several factors including baseline viral load. For baseline viral load, the RHs were 0.95 (95% CI, 0.84-1.07) and 0.65 (95% CI, 0.58-0.74), for 10 000 to 99 999 and 100 000 copies/mL or greater, respectively, compared with less than 10 000 copies/mL, but the probability of viral load lower than 500 copies/mL at week 32 was similar in all 3 groups. Subsequent rebound above 500 copies/mL was no more likely with a lower baseline CD4 cell count or higher viral load. CONCLUSION: In this study, lower CD4 cell counts and higher viral loads at baseline were not associated with poorer virological outcome of ART. Those with baseline viral loads of greater than 100 000 copies/mL had a slower rate of achieving viral suppression.

Adult↗

PubMed2001

Importance of mental health assessment in HIV-infected outpatients.

HIV infection, even when well controlled, may be associated with important mental health problems. We sought to investigate anxiety, depression, and health-related quality of life using screening measurements in patients with HIV infection and to examine their dependency on biosocial parameters relating to HIV. Prospective clinical, virologic, and immunologic data were obtained in a cross-sectional study within the Swiss HIV Cohort Study. Four self-reported questionnaires were used in 397 HIV-infected individuals. The scores for anxiety and depression were high as measured by the Hospital Anxiety and Depression Scale (HADS) and the State Trait Anxiety Inventory (STAI). Half the population scored <75 on a visual analog scale (VAS) Patients were also affected in their quality of life as measured by the HIV Medical Outcome Study (HIV-MOS). Almost all scores were significantly worse for intravenous drug users compared with other transmission groups. People who were employed, with a higher education or with higher CD4 count tended to score better, whereas those who had been hospitalized within the last 6 months, infected for a longer time, with higher viral load, or loss of weight scored significantly worse. A multivariate analysis showed higher education, being employed, low viral load, female gender, and shorter HIV disease duration to be associated with better scores. This study highlights the importance of mental health assessment regardless of HIV-disease parameters.

Adolescent↗

PubMed2001

Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study.

BACKGROUND: Data on adverse events to antiretroviral treatment have been recorded in clinical trials, post-marketing analyses, and anecdotal reports. Such data might not be an up-to-date or comprehensive assessment of all possible treatment combinations defined as potent antiretroviral treatment. METHODS: Using a standard clinical and laboratory method, we assessed prevalence of adverse events in 1160 patients who were receiving antiretroviral treatment. We measured the toxic effects associated with the drug regimen (protease inhibitor [PI], non-nucleoside and nucleoside analogue reverse transcriptase inhibitor) and specific compounds using multivariate analyses. FINDINGS: 47% (545 of 1160) of patients presented with clinical and 27% (194 of 712) with laboratory adverse events probably or definitely attributed to antiretroviral treatment. Among these, 9% (47 of 545) and 16% (30 of 194), respectively, were graded as serious or severe. Single-PI and PI-sparing-antiretroviral treatment were associated with a comparable prevalence of adverse events. Compared with single-PI treatment, use of dual-PI-antiretroviral treatment and three-class-antiretroviral treatment was associated with higher prevalence of adverse events (odds ratio [OR] 2.0 [95% CI 1.0-4.0], and 3.9 [1.2-12.9], respectively). Compound specific associations were identified for zidovudine, lamivudine, stavudine, didanosine, abacavir, ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, and nevirapine. INTERPRETATION: We recorded a high prevalence of toxic effects attributed to antiretroviral treatment for HIV-1. Such data provides a reference for regimen-specific and compound-specific adverse events and could be useful in postmarketing analyses of toxic effects.

Adult↗

PubMed2001

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

BACKGROUND: Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. QUESTIONS UNDER STUDY: (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. SETTING: The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. METHODS: Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. RESULTS: 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). CONCLUSION: Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

AIDS-Related Opportunistic Infections↗

PubMed2001

Alternative strategies for anti-HIV treatment.

New HIV treatment strategies are needed. Over the past year, substantial progress has been made in the development of new antiretroviral agents, although the journey from drug discovery to wide clinical use is completed by only a small number of medications. Strategies to enhance immune control and either discontinue or decrease the need for prolonged HAART are under study. The promising preliminary results in very early PHI are in contrast with the minor successes in chronic infection.

AIDS Vaccines↗

PubMed2000

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.

Adolescent↗

PubMed2000

Performance of five different assays for the quantification of viral load in persons infected with various subtypes of HIV-1. Swiss HIV Cohort Study.

Five methods for the assessment of plasma viral load (VL) were evaluated in 103 seropositive patients infected with various subtypes of HIV-1. The methods included three RNA-based assays (Amplicor Monitor 1.5, Quantiplex version 2.0, NucliSens), one ultrasensitive reverse transcriptase (PERT) assay and one "boosted" p24 antigen (Ag) enzyme immunoassay (EIA). Subtyping was based on sequencing in env. The sensitivities were, in decreasing order, Amplicor > PERT > p24 Ag > NucliSens > Quantiplex. The low sensitivity of NucliSens was related to the missing of several non-B (A, E, F, G) or recombinant strains, whereas that of Quantiplex did not depend on subtype. In the 1 group O sample and 4 group M samples, only PERT assay or p24Ag EIA produced a positive result. In the quantitative range, correlation was best between Amplicor and Quantiplex (r = 0.8848), fair between Amplicor and NucliSens (r = 0.7064) or PERT assay (r = 0.7266), lowest between Amplicor and p24Ag EIA (r = 0.3989). Amplicor underestimated VL in 1 subtype E sample. Thus, Amplicor performed best in terms of sensitivity (compared with all other assays) and accuracy (compared with NucliSens, PERT assay, and p24Ag) for non-B subtypes in group M samples. PERT assay appears useful for VL assessment in infections by group O or other highly divergent viruses.

HIV Infections↗

PubMed2000

Quantitation of human immunodeficiency virus type 1 RNA in different biological compartments.

Little information is available describing viral loads in body fluids other than blood. In addition, the suitability of commercially available assays for human immunodeficiency virus type 1 (HIV-1) RNA quantitation has not been evaluated in most nonblood fluids. We compared Organon Teknika's nucleic acid sequence-based amplification method (NASBA) and Roche's Amplicor HIV-1 Monitor (reverse transcriptase PCR [RT-PCR]) for quantitating HIV-1 RNA in cerebrospinal fluid (CSF), saliva, breast milk, seminal plasma, and cervical-vaginal lavage fluid (CVL). Saliva and breast milk frequently demonstrated some inhibition in the RT-PCR assay, similar to the inhibition previously described in seminal plasma. Inhibition of the RT-PCR assay was not observed with CSF or CVL, nor in any of the NASBA assays. When fluids from HIV-infected individuals were tested by RT-PCR and NASBA, 73 and 27% of CSF samples and 60 and 40% of breast milk specimens had detectable RNA, respectively. These differences were not statistically significant. In cross-sectional studies using RT-PCR to measure viral RNA in paired blood plasma and CSF samples, 71% of blood plasma samples and 42% of CSF samples were positive. A similar analysis using NASBA with paired blood plasma and CVL, saliva, or seminal plasma samples revealed 91% were blood plasma positive and 55% were CVL positive, 76% were blood plasma positive and 46% were saliva positive, and 83% were blood plasma positive and 63% were seminal plasma positive. NASBA worked fairly well to quantitate HIV-1 RNA from all fluids without apparent inhibition. RT-PCR performed well on CVL and CSF, frequently with greater sensitivity, although its use in other fluids appears limited due to the presence of inhibitors. These studies demonstrate that viral loads in nonblood fluids were generally lower than in blood.

Body Fluids↗

PubMed2000

Effects of genital tract inflammation on human immunodeficiency virus type 1 V3 populations in blood and semen.

We have examined cell-free viral populations in the blood plasma and seminal plasma compartments of men infected with subtype C human immunodeficiency virus type 1 (HIV-1) using the V3-specific heteroduplex tracking assay (V3-HTA). We studied two cohorts of subjects who had visited either a sexually transmitted disease (STD) clinic for genital tract inflammation in the form of urethritis (n = 43) or a dermatology clinic (controls, n = 14) in Malawi. We have previously shown that the presence of urethritis is associated with an eightfold increase in virus load in the seminal plasma compartment (M. S. Cohen et al., Lancet 349:1868-1873, 1997). The purpose of this study was to determine whether genital tract inflammation and its treatment caused genetic instability in cell-free HIV-1 populations. In a cross-sectional analysis at study entry, three-fourths of the STD and control subjects had multiple V3 populations in their blood while 60% of the STD subjects and 79% of the control subjects had multiple V3 populations in their semen. Overall, one-fourth of all of the subjects showed discordance between results with blood and semen specimens when samples were compared for the presence and absence of subpopulations. When differences in the relative levels of abundance of bands were also taken into account, two-fifths of all of the subjects showed discordance between the compartments. Among the subset of subjects in whom multiple virus populations could be detected, half showed discordance between the compartments. There were no differences between STD and control cohorts for these comparisons of the compartments in this cross-sectional analysis at study entry. Longitudinal analysis of the viral populations from two separate clinic visits over 1 to 4 weeks showed that the complexity of each V3 population as measured by Shannon entropy was different in blood and semen at the two time points, indicating that the blood and semen constitute different compartments for HIV-1. The seminal plasma compartment was more dynamic than the blood plasma compartment for the STD subjects who were treated for urethritis, with changes being noted in the presence or absence of V3-HTA bands in the semen of 29% of these subjects but in the blood of only 9% of these subjects. However, the changes were generally small. Overall, our results suggest that 40% of male subjects show discordance between seminal and blood viral populations and that the complexity of each V3 population was different between the two compartments. Both of these results point to the partial independence of the seminal compartment as a viral niche within the body.

Base Sequence↗

PubMed1999

Uniform risk of clinical progression despite differences in utilization of highly active antiretroviral therapy: Swiss HIV Cohort Study.

OBJECTIVE: To compare the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients according to sex, route of HIV acquisition and education, and to assess the impact of differences in utilization on the probability of progression to AIDS. DESIGN AND SETTING: Swiss HIV Cohort Study, a national prospective multi-centre study. PARTICIPANTS: A total of 3342 patients, including 1007 (30%) women. HIV was acquired through injection drug use in 1155 (35%) cases and through sex between men in 1172 (35%). Twenty-eight per cent (957) of participants had attained only the minimum level of schooling. At baseline, the median CD4 cell count was 269x10(6)/l cells, median HIV-1 RNA was 4.3 log10 copies/ml and 2917 (87%) were free of AIDS. METHODS: Kaplan-Meier life tables and Cox proportional hazards regression. RESULTS: During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men, hazard ratio 0.63 (95% confidence intervals 0.56-0.70) and in patients with minimum schooling compared with those with vocational training, hazard ratio 0.82 (0.75-0.91). The risk of progression to AIDS was similar among men and women, patients with a history of injecting drug use, and patients with lower educational attainment in both univariable and multivariable analysis. CONCLUSION: HIV-infected injecting drug users and those with lower levels of educational attainment start HAART later than other patient groups. The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression. This observation has important implications for treatment policy and the design of future clinical trials.

Acquired Immunodeficiency Syndrome↗

PubMed1999

AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study.

CONTEXT: Acquired immunodeficiency syndrome-related opportunistic illnesses (Ols) continue to occur after initiation of potent antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. Risk factors for clinical progression to Ols during potent therapy are not well defined. OBJECTIVE: To examine the incidence of and risk factors for Ols among patients treated with potent antiretroviral therapy in a population-based study. DESIGN: The Swiss HIV Cohort Study, a prospective cohort study of adult HIV-infected persons. SETTING: Seven study centers throughout Switzerland. PATIENTS: A total of 2410 cohort study participants with a potential follow-up of at least 15 months after starting potent therapy between September 1995 and December 1997. MAIN OUTCOME MEASURES: Disease-specific incidence of Ols during the 6 months preceding potent antiretroviral therapy and at 3 intervals after initiating therapy; risk factors for development of Ols during therapy. RESULTS: Of the 2410 participants, 143 developed 186 Ols after initiation of potent antiretroviral therapy. Incidence of any OI decreased from 15.1 per 100 person-years in the 6 months before therapy to 7.7 in the first 3 months after starting treatment, 2.6 in the following 6 months, and 2.2 per 100 person-years between 9 and 15 months. Reductions in incidence ranged from 38% per month for Kaposi sarcoma (P<.001) to 5% per month for non-Hodgkin lymphoma (P = .31). Baseline CD4 cell count continued to predict the risk of disease progression after initiating potent therapy. Compared with CD4 cell counts above 200 x 10(6)/L, the hazard ratio for developing Ols was 2.5 (95% confidence interval [CI], 1.4-4.5) for counts between 51 and 200 x 10(6)/L and 5.8 (95% CI, 3.2-10.5) for counts below 51 x 10(6)/L at baseline. Independent of baseline CD4 cell count, a rise in CD4 cell count by 50 x 10(6)/L or more and undetectable HIV-1 RNA in plasma (<400 copies/mL) by 6 months reduced risk of subsequent events, with hazard ratios of 0.32 (95% CI, 0.20-0.52) and 0.39 (0.24-0.65), respectively. CONCLUSIONS: Our data indicate that the risk of developing an OI for a person receiving potent antiretroviral therapy is highest during the initial months of therapy. Baseline CD4 cell count and immunologic and virologic response to treatment were strong predictors of disease progression in patients receiving potent therapy. Individuals with CD4 cell counts of 50 x 10(6)/L or below may need close clinical surveillance after initiation of potent therapy.

AIDS-Related Opportunistic Infections↗