Sundhiya Mandalia

Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome

Objectives Many questionnaires on adherence to antiretroviral therapy are in use, but the validity of patients’ responses has not been tested. The Medication Adherence Self-Report Inventory (MASRI) has been developed and tested for its validity against objective measures and treatment outcome. Design Prospective study comparing questionnaire responses with MEMS TrackCap (MC, a medication event monitoring system), pill count (PC) and plasma HIV viraemia in a publicly funded specialist HIV clinic. Participants Patients self-medicating antiretroviral therapy who were not cognitively impaired and were able to read and understand English. Results Mean adherence by MC of the 78 subjects was 92.9% (SE, 1.8%) and by PC 96.8% (SE, 1.4%). Agreement between MC and responses to items about doses missed 1, 2 or 3 days ago was low (κ = 0.23 (P < 0.03), 0.44 (P < 0.001) and 0.28 (P < 0.01) respectively). This improved when these responses were summated (κ = 0.46;P < 0.001) and was similar to that for recall of non-adherence over the preceding 2 weeks (κ = 0.54;P < 0.001). Mean self-reported adherence by visual analogue scale (VAS) over the preceding month was 93.3% (SE, 1.2%). This was strongly associated with both MC (r = 0.63;P < 0.001) and PC (r = 0.75;P < 0.001). On multivariate analysis, the strongest association between a MASRI item and MC was for the VAS. Both the 2 week recall and VAS items were inversely associated with viral load (P = 0.01). There was no association between dose timing (measured MC or questionnaire) or 3 day self-report and viral load. Conclusions The MASRI provides a means of measuring patient adherence that is valid when compared with objective measures.

Epidemiology and Predictive Factors for Chemokine Receptor Use in HIV-1 Infection

BACKGROUND CXCR4-using virus is associated with higher viral load and accelerated human immunodeficiency virus (HIV) disease progression. Additionally, CCR5 antagonists may not reduce the HIV-1 RNA load when mixed/dual-tropic or CXCR4-using virus is present. The determination of coreceptor tropism may be required before CCR5 or CXCR4 antagonists are initiated, unless reliable predictive markers of coreceptor use are established. METHODS Samples from treatment-naive and -experienced HIV-1-positive individuals with date-matched CD4 and CD8 cell counts and HIV-1 RNA, clade, and pol sequences were assessed for coreceptor usage, by use of the ViroLogic PhenoSense assay. RESULTS Coreceptor use determination was successful in 563 of 861 samples. Non-clade B virus was present in 18.6% of samples. CXCR4 or mixed/dual-tropic CCR5/CXCR4 virus was present in 112 of samples (19.9%). Only 4 samples (0.7%) showed exclusive CXCR4 use. In a multivariate model, higher CD4 cell count, lower viral load, and higher natural killer cell counts were significantly associated with CCR5 usage. No associations with treatment experience, clade, or pol gene mutations were observed. CONCLUSION The prevalence of CCR5-tropic HIV-1 phenotype declines with decreasing CD4 cell count and increasing viral load. Mixed/dual tropic virus is found in all CD4 cell count and viral load strata. Coreceptor usage is not influenced by viral clade.

Immune Reconstitution Inflammatory Syndrome Associated With Kaposi's Sarcoma

PURPOSE A proportion of patients with HIV infection who subsequently receive highly active antiretroviral therapy (HAART) exhibit a deterioration in their clinical status, despite control of virologic and immunologic parameters. This clinical response, known as the immune reconstitution inflammatory syndrome (IRIS), occurs secondary to an immune response against previously diagnosed pathogens. PATIENTS AND METHODS From our cohort of 5,832 patients treated in the HAART era, we identified 150 therapy-naive patients with a first presentation of Kaposis sarcoma (KS). Their clinicopathologic features and progress were recorded prospectively. RESULTS After commencing HAART, ten patients (6.6%) developed progressive KS, which we identify as IRIS-associated KS. In a comparison of these individuals with those whose KS did not progress, we found that IRIS-KS occurred in patients with higher CD4 counts (P = .03), KS-associated edema (P = .01), and therapy with both protease inhibitors and non-nucleosides together (P = .03). Time to treatment failure was similar for both groups, although the CD4 count declined more rapidly at first, in those patients with IRIS-associated KS. Despite this initial decline, in our clinical experience HAART could be successfully continued in those with IRIS-associated KS. CONCLUSION We have identified IRIS-KS in a cohort of HIV patients with KS who start HAART.

Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors.

ObjectiveTo evaluate the prevalence, outcome and possible risk factors for hyperlactataemia and lactic acidosis in HIV-positive persons receiving antiretroviral therapy. MethodsCross-sectional and longitudinal data from a prospectively collected clinical database. Associations with antiretroviral regimen, clinical and laboratory parameters were assessed using univariate and multivariate Coxs proportional hazards model. ResultsPatients naive to therapy and patients on current therapy for a minimum of 4 months were assessed. Median lactate was 1.1 mol/l in 253 untreated individuals and 1.4 mmol/l in 1239 patients stable on therapy for at least 4 months. At least two on-therapy samples were available for 750 of the 1239 individuals, taken a median 92 days apart. Lactate measurement showed a low positive predictive value of 38.9% but a high negative predictive value (98%) for normal values. Lactate was elevated ⩾ 2.4 mmol/l in 102 individuals on at least one occasion. In the multivariate Coxs proportional hazards model, no demographic characteristics were associated with hyperlactataemia. Didanosine-containing regimens doubled the relative hazard of hyperlacatæmia compared with those sparing didanosine. Abacavir-containing regimens reduced the hazard of hyperlactatæmia. Choice of thymidine analogue did not influence risk. Hyperlactatæmia was associated with acid–base disturbance. Use of didanosine and female sex were over-represented amongst nine patients with severe hyperlactataemia (> 5 mmol/l) or lactic acidosis. ConclusionsScreening of lactate is of limited use in asymptomatic individuals on antiretroviral therapy. Raised lactate represents part of a spectrum of lactate and acid–base disturbance that infrequently includes lactic acidosis. Didanosine appears associated with an increased risk of hyperlactataemia.

A meta-analysis of transient elastography for the detection of hepatic fibrosis.

Objectives The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. Methods Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (≥F2) and cirrhosis (F4). Results A total of 22 studies were selected comprising 4430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (≥F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). Conclusions Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.

Renal dysfunction with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy regimens is not observed more frequently: a cohort and case-control study.

Background:Tenofovir disoproxil fumarate (tenofovir DF), the first nucleotide analogue reverse transcriptase inhibitor approved for the treatment of HIV infection, has been associated with renal dysfunction in isolated cases. We investigated the overall incidence and risk of renal dysfunction in individuals receiving tenofovir DF and compared this with other antiretrovirals. Methods:Data from the Chelsea and Westminster cohort were analyzed to reveal HIV-positive individuals with a creatinine value greater than 120 μmol/L at any time, the upper limit of normal used by our reference laboratory. These individuals were classified according to antiretroviral exposure and time exposed. A matched case-control study was performed comparing patients who had received tenofovir DF and subsequently developed a creatinine value greater than 120 μmol/L against controls who had been treated with tenofovir DF and had not experienced a creatinine elevation. Results:Of 4183 HIV-positive patients, 1175 were identified as having a recorded creatinine value >120 μmol/L. Comparison of antiretroviral-naive patients and patients exposed to tenofovir DF- and non-tenofovir DF-containing regimens revealed a lower rate ratio and probability of developing a creatinine value >120 μmol/L in patients exposed to tenofovir DF (rate ratio vs. no antiretrovirals = 0.22, 95% confidence interval [CI]: 0.07-0.69; P < 0.001) with no significant difference between HAART regimens, corrected for duration of exposure. Of the 1058 individuals who were exposed to tenofovir DF, 84 (8%) patients experienced a creatinine value >120 μmol/L subsequent to exposure. An alternative etiology of renal dysfunction was found in 75 (90%) of these individuals. Conclusions:Tenofovir DF is not associated with renal dysfunction more frequently than other antiretroviral drugs, and the occurrence of renal dysfunction in this context is usually attributable to other causes.

Increased numbers of acute hepatitis C infections in HIV positive homosexual men; is sexual transmission feeding the increase?

Although the principal mode of hepatitis C (HCV) transmission in the United Kingdom is injecting drug use (IDU), the risk for a third of infections is unknown.1 The contribution of sexual transmission between men who have sex with men (MSM) to the spread of hepatitis C is unclear, however evidence is accumulating that both co-infection with HIV2 and the presence of other sexually transmitted infections (STIs) facilitate sexual transmission of HCV.3 With the reported increases in unsafe sex and STIs in HIV positive MSM we questioned whether these circumstances may lead to an increase in the number of HCV infections. This study was undertaken to determine whether within our clinics, changes in the number of individuals being diagnosed with acute HCV infection were occurring and to ascertain risk factors for acquisition in these individuals. A case note review of all patients within the HIV and sexual health clinics of St Stephen’s Centre with diagnosed acute HCV infection between January …

Transmission of hepatitis C virus among HIV-positive homosexual men and response to a 24-week course of pegylated interferon and ribavirin.

Objective:To evaluate treatment outcome of acute hepatitis C virus (HCV) in HIV-positive individuals. Design:Open-label, prospective study conducted in London, January 1997-December 2003. Methods:Patients in whom acute HCV infection had been diagnosed had sequential HCV RNA levels measured at 0, 4, 12, 24, 32, and 48 weeks. If HCV RNA positive at 12 weeks, patients were offered pegylated interferon α-2b 1.5 μg/kg/wk and ribavirin 800-1200 mg/d for 24 weeks. Patients with increasing HCV RNA titers were offered treatment earlier. Results:Fifty male homosexuals with a mean age 37 years were identified: 44 from abnormal liver function test results, 4 from sexual contact with an HCV-positive partner, and 2 at HIV seroconversion. Overall, 12 individuals became HCV RNA negative spontaneously. This was significantly associated with high baseline median CD4+ count (P = 0.029), CD4+ count >500 cells/mm3 (P = 0.017), and lower HCV RNA titers (P = 0.017). Only 27 patients accepted treatment, 16 (59%) of whom reached sustained virologic response. This was associated with higher peak mean alanine aminotransferase (P < 0.001) and higher baseline CD4% (P = 0.041). Conclusions:Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than in HIV-negative subjects. Because a high percentage of individuals seroconvert spontaneously, treatment should be delayed until after 12 weeks.

Cost-Effectiveness of Highly Active Antiretroviral Therapy in South Africa

Background Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. Methods and Findings Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, US

Effect of computer-assisted self interviews on reporting of sexual HIV risk behaviours in a general population sample: a methodological experiment

1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of