Sara Madge

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre.

ObjectiveTo describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SubjectsA total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). ResultsThe median CD4 count at starting HAART was 171 × 106 cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years;P = 0.0008], as were previously treatment-naive patients (RH, 0.65;P = 0.0050), those in a clinical trial (RH, 0.64;P = 0.027) and those who started nelfinavir (RH, 0.57;P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41;P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51;P < 0.0001) were more likely to modify HAART. ConclusionsThere was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

Tenofovir‐associated renal and bone toxicity

Objectives The aims of the study were to describe the clinical presentation and renal and bone abnormalities in a case series of HIV‐infected patients receiving treatment with tenofovir (TDF), and to recommend appropriate screening for toxicity related to TDF.

Reduced bone mineral density in HIV positive individuals

A total of 105 HIV-positive patients underwent dual-energy X-ray absorbtiometry (DEXA) scan to assess bone mineral density (BMD). The prevalence of reduced BMD was found to be 71% and was higher in patients who had ever been treated with protease inhibitors (PI). Our results suggest a possible association between PI and reduced BMD, and further complicate the debate regarding when to commence treatment of HIV and with what agents to start.

Factors Influencing Increases in CD4 Cell Counts of HIV-Positive Persons Receiving Long-Term Highly Active Antiretroviral Therapy

BACKGROUND Highly active antiretroviral therapy (HAART) results in an improvement in immunologic function. We sought to investigate the factors associated with increases in CD4 cell count among human immunodeficiency virus (HIV)-positive antiretroviral-naive patients starting HAART. METHODS Five hundred ninety-six subjects were followed for a median of 2.5 years (interquartile range, 1.0-4.0 years). Factors associated with changes in CD4 cell counts in the first 3 months of HAART and from 3 months onwards were analyzed. RESULTS After 6, 12, and 24 months of HAART, the median increases in CD4 cell counts were 114, 181, and 248 cells/mm3, respectively; 84%, 84%, and 80% of subjects had a virus load of <400 copies/mL during the same periods. White ethnicity, higher pre-HAART virus load, and lower pre-HAART CD4 and CD8 cell counts were associated with greater increases in CD4 cell counts during the first 3 months of HAART. From 3 months onward, a greater cumulative proportion of time spent with virus load <400 copies/mL was associated with a more favorable change in CD4 cell count (an average increase of 5.2 cells/mm3/year [95% confidence interval [CI], 3.8-6.7 cells/mm3/year] for each extra 10% cumulative time spent with a virus load <400 copies/mL) (P<.0001). For every 100 cells/mm3 higher in baseline CD4 cell count, the increase was 6 cells/mm3/year less (95% CI, 2-11 cells/mm3/year) (P=.02). Sex, risk group, age, and HAART regimen were not associated with increases in CD4 cell counts. CONCLUSIONS These findings emphasize the importance of maintaining virological suppression and suggest other factors that influence long-term CD4 cell response.

Immunological, virological and clinical response to highly active antiretroviral therapy treatment regimens in a complete clinic population

BackgroundHighly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. ObjectivesTo describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a single treatment centre. MethodsKaplan–Meier estimation and incidence rates were used to describe responses to HAART (a protease inhibitor or non-nucleoside drug in addition to at least two nucleoside analogues) among 421 patients from the Royal Free Hospital in London. ResultsThe median CD4 cell count at starting HAART was 186 × 106 cells/l [interquartile range (IQR) 76–310] and viral load was 5.13 log10 copies/ml (IQR 4.66–5.56). At 6 months after starting HAART, 51.1% of patients were estimated to have experienced a 100 × 106 cells/l increase in CD4 cell count; the median time for viral load to fall below 400 copies/ml was 3.7 months (95% confidence interval 3.2–4.4). At 6 months after the first viral load was < 400 copies/ml, 16.4% of patients were estimated to have failed on the basis of a single viral load > 400 copies/ml and 12.4% were estimated to have failed if the more stringent definition of two viral loads above the limit of detection was used. Compared with the pre-HAART era, the incidence of death among patients on HAART was one sixth of that level; new AIDS-defining illnesses was one seventh; and hospital admissions was one fifth. In total, 141 patients (33.5%) stopped at least one of the antiretroviral agents included as part of their HAART regimen; the occurrence of side effects was the most common reason (n = 63; 44.7%). ConclusionA good response occurred to an initial HAART regimen. There was a high rate of virological relapse, which varied considerably according to the definition of failure used. Even so, the rates of clinical progression and hospital admissions observed to date were low. Further follow-up of these patients is required to determine their long-term immunological, virological and clinical outcome.

Gender differences in virologic response to treatment in an HIV-positive population : A cohort study

Objective: To establish whether a gender difference in virologic response to highly active antiretroviral treatment (HAART) exists. Methods: A cohort of HIV‐positive individuals was examined. Outcomes: Achievement of viral load <500 copies/ml and “failure” (failure to suppress viral load <500 copies/ml after 24 weeks or two consecutive measurements above this level after having suppressed below it). Hazard ratios (HRs) comparing the rate in women to that in men were derived using the Cox model. Results: Of 366 male subjects, 79% were white and 82% were homosexual. Sixtythree percent of the 91 female subjects were African and 87% were heterosexual. The median follow‐up after HAART was 94 weeks. The baseline CD4 count was higher in men (228 × 106 per liter) than in women (171 × 106 per liter) (p = .01), but the viral load was similar (p = .88). The median time to <500 copies/ml was 16 weeks. Women achieved a viral load of <500 copies/ml at a faster rate than men, with an adjusted HR of 1.46 (95% confidence interval [CI]: 0.99‐2.16; p = .06). Some 261 patients failed treatment (58% of men and 53% of women) with an HR of 0.78 (95% CI: 0.51‐1.21; p = .27). Conclusions: Women may achieve virologic suppression at a faster rate than men and have a more durable response. Further research should examine these responses in conjunction with clinical outcomes, because gender differences in virologic response may ultimately be of little relevance if clinical outcomes are similar.

Highly active antiretroviral therapy and cervical intraepithelial neoplasia

Highly active antiretroviral therapy (HAART) has improved HIV prognosis, but its effect on cervical intraepithelial neoplasia (CIN), which is associated with HIV, is uncertain. Among 71 HAART-treated women the prevalence of CIN before HAART was 55%. After a median of 10 months after starting HAART the prevalence had increased to 62% (P = 0.20); 13% of patients experienced regression of a CIN lesion, and this was most strongly associated with a greater increase in CD4 cell count. Such studies will provide the basis for guidelines for monitoring CIN in HIV-positive women in the HAART era.

Changes in CD4 lymphocyte counts after interruption of therapy in patients with viral failure on protease inhibitor-containing regimens

ObjectiveTo describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. MethodsWe studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. ResultsOverall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (−0.66, P = 0.0002). ConclusionPatients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption

An audit of antiretroviral treatment use in HIV‐infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.

No association between HIV disease and its treatment and thyroid function

The aims of the study were (i) to investigate the prevalence of overt and subclinical thyroid disease in HIV‐positive patients in a London teaching hospital; (ii) to determine risk factors associated with the development of thyroid dysfunction, including highly active antiretroviral therapy (HAART) and individual antivirals, and (iii) to determine the occurrence of thyroid dysfunction longitudinally over 3 years.