Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
HIV Med ; 22(8): 770-774, 2021 09.
Article in English | MEDLINE | ID: mdl-33964099

ABSTRACT

OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Adult , Anti-HIV Agents/adverse effects , Anti-Retroviral Agents/adverse effects , Drug Therapy, Combination , HIV Infections/drug therapy , Humans , Male , Viral Load
2.
HIV Med ; 19(1): 65-71, 2018 01.
Article in English | MEDLINE | ID: mdl-28703491

ABSTRACT

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , CCR5 Receptor Antagonists/administration & dosage , Cyclohexanes/administration & dosage , Drug Substitution , HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/administration & dosage , Triazoles/administration & dosage , Adult , Antiretroviral Therapy, Highly Active/adverse effects , CCR5 Receptor Antagonists/adverse effects , Cyclohexanes/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , HIV Protease Inhibitors/adverse effects , HIV-1/isolation & purification , Humans , Maraviroc , RNA, Viral/blood , Reverse Transcriptase Inhibitors/adverse effects , Treatment Outcome , Triazoles/adverse effects , Viral Load
3.
Int J STD AIDS ; 27(10): 901-5, 2016 09.
Article in English | MEDLINE | ID: mdl-26792282

ABSTRACT

A retrospective clinical audit was performed to assess if the British HIV Association 2011 guidelines on routine screening for tuberculosis in HIV are being implemented in a large UK urban clinic, and if a tuberculosis-screening prompt on the electronic patient record for new attendees was effective. Of 4658 patients attending during the inclusion period, 385 were newly diagnosed first-time attendees and routine tuberculosis screening was recommended in 165. Of these, only 6.1% of patients had a completed tuberculosis screening prompt, and 12.1% underwent routine tuberculosis screening. This audit represents the first published UK data on routine screening rates for tuberculosis in HIV and demonstrates low rates of tuberculosis screening despite an electronic screening prompt designed to simplify adherence to the national guideline. Reasons why tuberculosis screening rates were low, and the prompt ineffective, are unclear. A national audit is ongoing, and we await the results to see if our data reflect a lack of routine tuberculosis screening in HIV-infected patients at a national level.


Subject(s)
Clinical Audit , Guideline Adherence/statistics & numerical data , HIV Infections/complications , Mass Screening/methods , Tuberculosis/diagnosis , Adult , Electronic Health Records , Female , HIV Infections/diagnosis , Humans , Male , Mass Screening/standards , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Tuberculosis/complications , Tuberculosis/epidemiology , United Kingdom/epidemiology
4.
HIV Med ; 12(4): 219-27, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20812949

ABSTRACT

BACKGROUND AND OBJECTIVES: Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/µL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. METHODS: Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. RESULTS: IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/µL (IL-2 arm) and 463cells/µL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/µL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively. CONCLUSIONS: Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , HIV Infections/drug therapy , HIV-1 , Interleukin-2/therapeutic use , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/drug therapy , AIDS-Related Opportunistic Infections/virology , Adjuvants, Immunologic/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Drug Therapy, Combination , Female , HIV Infections/virology , Humans , Male , Middle Aged , Pneumonia, Bacterial/virology , Predictive Value of Tests , Recombinant Proteins , Viral Load
5.
HIV Clin Trials ; 7(2): 70-85, 2006.
Article in English | MEDLINE | ID: mdl-16798622

ABSTRACT

BACKGROUND: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells > or =300 cells/microL. OBJECTIVES: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. METHOD: Baseline characteristics of randomized participants were summarized by region. RESULTS: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/muL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). CONCLUSION: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability.


Subject(s)
Anti-HIV Agents/therapeutic use , Data Collection/statistics & numerical data , HIV Infections/drug therapy , HIV-1 , Interleukin-2/analogs & derivatives , Randomized Controlled Trials as Topic/statistics & numerical data , Adult , Antiretroviral Therapy, Highly Active , Ethnicity/statistics & numerical data , Female , Global Health , HIV Infections/complications , Hepatitis B/complications , Hepatitis C/complications , Humans , Injections, Subcutaneous , Interleukin-2/administration & dosage , Interleukin-2/therapeutic use , Male , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Sexual Behavior/statistics & numerical data , Treatment Outcome , Women's Health
6.
J Clin Virol ; 22(3): 289-95, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11564594

ABSTRACT

BACKGROUND: There is renewed interest in the use of immunotherapy as an adjunct to antiretrovirals (ART) in the treatment of HIV disease. Most work has been performed on interleukin-2 (IL-2). There is considerable evidence from numerous phase II studies that intermittent dosing of subcutaneous IL-2 plus antiretroviral therapy (ART) produces a sustainable rise in the CD4(+) T-lymphocyte count which exceeds that which can be achieved using ART alone, without any adverse effect on plasma HIV RNA. However, the immunological competency and therefore clinical impact of this expanded CD4(+) T cell pool is yet to be established; this question is the focus of two large clinical end-point studies, ESPRIT and SILCAAT. OBJECTIVE: Prior to the establishment of ESPRIT, four 'Vanguard' studies were undertaken; the UK Vanguard examined the safety and virological/immunological aspects of intermittent subcutaneous IL-2 without the use of ART in HIV-1 ART naïve patients with a baseline CD4(+) T cell count of > or = 350cells/mm(3). DESIGN: The UK Vanguard was an open-label, randomised study comparing subcutaneous (s/c) IL-2 at either 4.5MIU or 7.5MIU q12h for 5 days every 8 weeks versus no therapy in HIV-1-infected individuals. Primary endpoints included mean area under the curve change from baseline CD4(+) T cell count and plasma log HIV-RNA. RESULTS: Thirty six subjects were enrolled into the three arms of the UK Vanguard study. Results showed significant differences in the area under the curve (AUC) change from baseline CD4(+) T cell count (P = 0.001) and changes in mean absolute CD4(+) T cell count (P = 0.04) and no significant difference in mean AUC change from baseline plasma HIV-RNA (P = 0.48) at 24 weeks between the IL-2 and control arms respectively. The significance of these results and those from other studies on the use of IL-2 in HIV disease are discussed.


Subject(s)
Adjuvants, Immunologic/therapeutic use , HIV Infections/therapy , HIV-1 , Interleukin-2/therapeutic use , Adjuvants, Immunologic/administration & dosage , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , Drug Therapy, Combination , Female , HIV Infections/blood , HIV Infections/virology , HIV-1/genetics , HIV-1/isolation & purification , Humans , Injections, Subcutaneous , Interleukin-2/administration & dosage , Male , RNA, Viral/blood , Viral Load
7.
AIDS Res Hum Retroviruses ; 17(13): 1293-6, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11559430

ABSTRACT

A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapine (NVP). Longitudinal analysis of samples revealed that this deletion emerged upon reinitiation DDI/D4T therapy following a toxicity-induced short discontinuation of all antiretrovirals. Analysis of the resistance phenotype showed a greater than 62-fold increase of the IC50 of NVP, but no significant change in sensitivity to other single nonnucleoside reverse transcriptase inhibitors (NNRTIs). The mutated virus showed only a moderately reduced sensitivity to DDI (6.7-fold) and D4T (4.8 fold). In a subsequent sample 3 months later additional RT mutations were found, including A62V, Y188L, and Q151M, conferring high-level cross-resistance to multiple nucleoside analogs. Our findings provide evidence that the deletion of RT residue 69 selectively confers high-level NVP resistance.


Subject(s)
Drug Resistance, Viral/genetics , HIV Reverse Transcriptase/genetics , HIV Reverse Transcriptase/metabolism , HIV-1/enzymology , Nevirapine/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Sequence Deletion/genetics , Adult , Anti-HIV Agents/pharmacology , HIV Infections/drug therapy , HIV Infections/virology , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/drug effects , HIV-1/genetics , Humans , Inhibitory Concentration 50 , Male , Molecular Sequence Data , Phenotype , Selection, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL
...