Acquired Immunodeficiency Syndrome: Fisher M

Fisher M, Benn P, Evans B, Pozniak A, Jones M, Maclean S, Davidson O, Summerside J, Hawkins D, Anonymous00359. · Department of Genitourinary Medicine, Royal Sussex County Hospital, Brighton, UK. · Int J STD AIDS. · Pubmed #16464267 No free full text.

Abstract: We present the British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis after sexual exposure (PEPSE) to HIV. This document includes a review of the current data to support the use of PEPSE, considers how to calculate the risks of HIV infection after a potential exposure, and provides recommendations on when PEPSE would and would not be considered. Other areas included are the possible impact on sexual behaviour, cost-effectiveness, and issues relating to service provision. Throughout the document, consideration is given to the place of PEPSE within the broader context of HIV prevention strategies and sexual health.

Heyns CF, Fisher M. · Department of Urology, University of Stellenbosch and Tygerberg Hospital, Tygerberg, South Africa. · BJU Int. · Pubmed #15784082 No free full text.

Abstract: In people infected with the human immunodeficiency virus (HIV) both the CD4 T-cell count and the viral load are used to monitor disease progression to acquired immunodeficiency syndrome (AIDS). CD4 counts of <500/mm(3) are associated with opportunistic infections and certain malignancies, so-called 'AIDS-defining' conditions. Highly active antiretroviral therapy, using combinations of reverse transcriptase inhibitors and/or protease inhibitors, can improve considerably the prognosis of people who are HIV-positive, but such therapy is not yet widely available in many developing countries. People with AIDS are predisposed to urinary tract infection (UTI) by uncommon bacteria and pathogens, e.g. fungi, parasites and viruses, which may affect any urogenital organ; treatment should be culture-specific and long-term, because there is a tendency to recurrence, infection with multiple organisms and resistant isolates. Voiding dysfunction in patients with AIDS is usually a result of neurological complications caused by opportunistic infections, and has a poor prognosis. Of patients with AIDS, 30-50% develop a cancer, especially Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL). KS may involve any urogenital organ, but is usually part of systemic disease. Small lesions on the external genitalia can be treated with laser, cryotherapy or surgical excision, larger lesions with radiotherapy, and disseminated or visceral KS with multidrug chemotherapy. NHL may involve the kidneys, testes and retroperitoneal lymph nodes, thus obstructing the ureters, which may require ureteric stenting or percutaneous nephrostomy. NHL can be treated with radiotherapy and combination chemotherapy. Urolithiasis in patients with AIDS may be caused by indinavir, a protease inhibitor, but the more common types of stones may also occur. Fluid-electrolyte and acid-base disturbances are common in patients with advanced AIDS, secondary to vomiting, diarrhoea, malnutrition or septicaemia. HIV-associated nephropathy occurs in 10-30% of patients, and often leads to renal failure. Testicular atrophy is common, leading to infertility, erectile dysfunction (ED) and decreased libido. Treatment for ED must include counselling about strategies to reduce the transmission of HIV. The risk of HIV transmission after parenteral exposure to blood from an HIV-positive patient is relatively low (0.2-0.4%); the urologist can reduce the risk of transmission during surgery by adopting certain precautions. After occupational exposure to HIV, chemoprophylaxis with antiretroviral medication can significantly reduce the probability of HIV transmission.

Dunn DT, Green H, Loveday C, Rinehart A, Pillay D, Fisher M, McCormack S, Babiker AG, Darbyshire JH, Anonymous00384. · HIV Division, Medical Research Council Clinical Trials Unit, London, United Kingdom. · J Acquir Immune Defic Syndr. · Pubmed #15793365 No free full text.

Abstract: OBJECTIVES: To assess the clinical utility of phenotypic resistance testing in addition to genotypic resistance testing among HIV-1-infected patients experiencing virologic failure and with limited therapeutic options. DESIGN: Multicenter randomized trial. METHODS: Patients were eligible if a decision had been made to switch antiretroviral therapy, the most recent HIV-1 RNA plasma viral load (VL) exceeded 2000 copies/mL, and the clinician was unable to select a potent regimen of 3 or more drugs without access to a resistance test. Subjects were randomized to genotypic resistance testing alone (G arm) or to genotypic plus phenotypic testing (G + P arm). Patients had access to resistance testing at any time during follow-up (minimum of 1 year) according to the original allocation. The primary end point was change in plasma VL from baseline at 12 months. RESULTS: Three hundred eleven patients were recruited between February 2000 and July 2001. At baseline, mean VL and CD4 count were 4.23 log10 copies/mL and 275 cells/mm, respectively, and subjects had previous exposure to a mean of 7.7 antiretroviral drugs. There was no appreciable difference between the study arms in the drug regimens prescribed after randomization. Mean reduction in VL load at 12 months was similar in the 2 arms (G: 1.37 log10 reduction, G + P: 1.28 log10 reduction; P = 0.77), as was the proportion of subjects with VL <50 copies/mL (G: 35%, G + P: 27%). CONCLUSION: The study did not demonstrate added value of phenotypic resistance testing in conjunction with genotypic resistance testing in patients with limited therapeutic options.

Youle M, Tyrer M, Fisher M, Lampe F, Wilson D, Ransom D, Story A, Mocroft A, Loveday C, Johnson MA, Phillips AN. · Royal Free Centre for HIV Medicine, Royal Free & University College Medical School, London, United Kingdom. · J Acquir Immune Defic Syndr. · Pubmed #11782591 No free full text.

Abstract: In most studies, people who have not responded virologically to a protease inhibitor (PI)-containing regimen have tended to experience poor virologic responses to subsequent regimens. We describe the 2-year viral load, CD4 count, and clinical outcome of a multidrug regimen used in 60 people who had not responded virologically to a PI-containing regimen. At baseline, median CD4 count was 126/mm(3) (nadir 30/mm(3) ) and median viral load was 320,000 copies/mL. A median of five antiretroviral drugs had previously been used, of which a median of two were PIs. Of these patients, 16% had previously used another nonnucleoside reverse transcriptase inhibitor besides efavirenz. The multidrug regimen (median 5 drugs) started most commonly included efavirenz (100%), at least one PI (92%, usually indinavir/ritonavir), didanosine (78%), and hydroxyurea (74%). At year 2, 5 patients had died and 5 had no measure available. Nine patients developed a new AIDS event and 10 patients were known to have stopped all antiretroviral therapy. Thirty-one patients (52% of the whole group, 72% of those remaining on therapy with viral load value available) had viral load <50 copies/mL. Thus, a substantial proportion of patients who had failed to respond virologically to PI-containing regimens can achieve profound and sustained virologic suppression with a multidrug regimen.

Phillips AN, Gazzard B, Gilson R, Easterbrook P, Johnson M, Walsh J, Leen C, Fisher M, Orkin C, Anderson J, Pillay D, Delpech V, Sabin C, Schwenk A, Dunn D, Gompels M, Hill T, Porter K, Babiker A, Anonymous00278. · Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK. · AIDS. · Pubmed #17690569 No free full text.

Abstract: OBJECTIVE: To assess the absolute rate of AIDS and death in antiretroviral therapy (ART)-naive patients with a high CD4 cell count. Such information would be helpful in the design of a trial investigating early initiation of ART. DESIGN: Analysis of data from an ongoing HIV cohort study. METHODS: The rate of (severe) AIDS or death and death alone was evaluated in ART-naive patients according to the current CD4 cell count, focusing on CD4 cell counts > or = 350 cells/microl among patients in the UK CHIC Study. RESULTS: In a total of 30 313 person-years of follow-up, there were 1557 AIDS or death events. The rate of AIDS or death in persons with most recent CD4 cell count 350-499, 500-649 and > 650 cells/microl was 2.49, 1.54 and 0.96 per 100 person-years, respectively. The rate ratio for those with CD4 cell count 500-649 cells/microl compared with those with CD4 cell count > or = 650 cells/microl was 1.55 [95% confidence interval (CI), 1.11-2.17; P = 0.01]. In a Poisson regression model based on person years with CD4 cell count > or = 350 cells/microl , there was a strong effect of CD4 cell count on rate of AIDS or death (rate ratio, 0.84; 95% CI, 0.76-0.93; P = 0.001), independent of viral load and age. CONCLUSIONS: The trend of decreasing rate of AIDS and death with higher CD4 cell count is present throughout the CD4 cell count > or = 350 cells/microl range in ART-naive people.

Holkmann Olsen C, Mocroft A, Kirk O, Vella S, Blaxhult A, Clumeck N, Fisher M, Katlama C, Phillips AN, Lundgren JD, Anonymous00238. · Copenhagen HIV Programme, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. · HIV Med. · Pubmed #17352766 No free full text.

Abstract: OBJECTIVES: The aim of the study was to compare incidence rates (IRs) of AIDS/death in patients with and without treatment interruption (TI) of combination antiretroviral therapy (cART) for periods of 3 months or more for different categories of CD4 cell count and viral load, and to determine risk factors for clinical progression to AIDS/death. METHODS: Patients starting cART with a CD4 cell count and a viral load available within 6 months of starting cART were included in the study. The IR and risk factors of TI were determined. We assessed the incidence rate ratios (IRRs) for TI and AIDS/death events using Poisson regression models. RESULTS: Of 3811 patients included in the study, 26% were ART-naïve prior to cART. The median date of starting cART was July 1997, the median CD4 cell count was 226 cells/microL and the median viral load was 4.36 log(10) HIV-1 RNA copies/mL. We observed 1243 interruptions and 403 AIDS-events/deaths. The IR of AIDS/death was higher in patients with lower CD4 cell counts or higher viral loads, regardless of TI. After adjusting for baseline factors, the IR of AIDS/death was significantly higher in the TI group than in the non-TI group [IRR 2.63; 95% confidence interval (CI) 2.01-3.44; P<0.0001]; this could be explained by current CD4 cell counts and viral loads, as the CD4 cell count- and viral load-adjusted IRR was 1.14 (95% CI 0.86-1.51; P=0.37). Within the TI group, patients with a current CD4 cell count of <200 cells/microL had a 3-fold higher risk of AIDS/death than those with a CD4 cell count of 200-350 cells/microL, whereas patients with a current CD4 cell count of >350 cells/microL had a 4-fold lower risk of disease progression. CONCLUSIONS: TI is common in clinical practice. The risk of AIDS/death increased more than 2-fold for patients stopping all cART regimen drugs for 3 months or more. Among patients experiencing a TI, those with low CD4 cell counts, high viral loads or prior AIDS had an increased risk of AIDS/death. Hence, TI should be discouraged and closely monitored if it occurs.

Fisher M, Wakefield S, Grossman H. · No affiliation provided · Posit Aware. · Pubmed #16791963 No free full text.

This publication has no abstract.