HIV Seropositivity: Pillay D

Pozniak A, Gazzard B, Anderson J, Babiker A, Churchill D, Collins S, Fisher M, Johnson M, Khoo S, Leen C, Loveday C, Moyle G, Nelson M, Peter B, Phillips A, Pillay D, Wilkins E, Williams I, Youle M, Anonymous00074. · Chelsea and Westminster Hospital, London, UK. · HIV Med. · Pubmed #14511246 No free full text.

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Gow PJ, Pillay D, Mutimer D. · Liver and Hepatobiliary Unit, Third Floor, Nuffield House, Queen Elizabeth Hospital, Birmingham, England. · Transplantation. · Pubmed #11477334 No free full text.

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Brown AE, Murphy G, Rinck G, Clewley JP, Hill C, Parry JV, Johnson AM, Pillay D, Gill ON. · HIV/STI Department, Health Protection Agency Centre for Infections, London, UK. · Sex Transm Infect. · Pubmed #18955386 No free full text.

Abstract: OBJECTIVES: Laboratory, clinical and sequence-based data were combined to assess the differential uptake of voluntary confidential HIV testing (VCT) according to risk and explore the occurrence of HIV transmission from individuals with recently acquired HIV infection, before the diagnostic opportunity. METHODS: Between 1999 and 2002, nearly 30,000 anonymous tests for previously undiagnosed HIV infection were conducted among men who have sex with men (MSM) attending 15 sentinel sexually transmitted infection (STI) clinics in England, Wales and Northern Ireland. Using a serological testing algorithm, undiagnosed HIV-infected men were categorised into those with recent and non-recent infection. VCT uptake was compared between HIV-negative, recently HIV-infected and non-recently HIV-infected men. A phylogenetic analysis of HIV pol sequences from 127 recently HIV-infected MSM was conducted to identify instances in which transmission may have occurred before the diagnostic opportunity. RESULTS: HIV-negative MSM were more likely to receive VCT at clinic visits compared with undiagnosed HIV-infected MSM (56% (14,020/24,938) vs 31% (335/1072); p<0.001). Recently HIV-infected MSM were more likely to receive VCT compared with those with non-recent infections (42% (97/229) vs 28% (238/844); p<0.001). 22% (95/425) of undiagnosed HIV-infected MSM with STI received VCT. Phylogenetic analysis revealed at least seven transmissions may have been generated by recently HIV-infected MSM: a group that attended STI clinics soon after seroconversion. CONCLUSIONS: The integration of clinical, laboratory and sequence-based data reveals the need for specific targeting of the recently HIV exposed, and those with STI, for VCT. VCT promotion alone may be limited in its ability to prevent HIV transmission.

Pillay D, Parry J. · Centre for Virology, University College London, United Kingdom. · Euro Surveill. · Pubmed #16687776 links to  free full text

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Pillay D, Bhaskaran K, Jurriaans S, Prins M, Masquelier B, Dabis F, Gifford R, Nielsen C, Pedersen C, Balotta C, Rezza G, Ortiz M, de Mendoza C, Kücherer C, Poggensee G, Gill J, Porter K, Anonymous00013. · Centre for Virology, Division of Infection and Immunity, Royal Free and University College Medical School, Windeyer Institute, 46 Cleveland Street, London W1T 4JF, UK. · AIDS. · Pubmed #16327315 No free full text.

Abstract: BACKGROUND: Transmission of drug-resistant HIV-1 is well recognized. However, the impact of such transmission on natural history of infection remains unknown. METHODS: Three hundred HIV-1-infected, antiretroviral-naive individuals, recruited between 1987 and 1993, and with resistance tests undertaken within 18 months of infection were assessed. We estimated the impact of transmitted drug resistance (TDR) on subsequent CD4 cell count decline in the absence of treatment. We also used Kaplan-Meier methods to assess the response to antiretroviral therapy based on the number of active drugs utilized (according to genotypic resistance results). RESULTS: Infection with any form of drug-resistant HIV-1 was associated with a steeper decline of CD4 cell count over the first year of infection. Estimated rates of decline in the first year were 5.0 [95% confidence interval (CI), 2.8-7.3] and 1.7 (95% CI, 0.8-2.6) radicalCD4 cells per year for TDR and no TDR, respectively (P = 0.005). For an individual at a CD4 cell count of 500 cells/microl at seroconversion, these rates correspond to a CD4 cell loss of 199 and 73 cells/microl, respectively, in the first year. Thereafter we found no evidence of a difference in the rate of CD4 cell decline (P = 0.32). Initiation of HAART after calendar year 2000, but not number of active drugs, was associated with improved responses. CONCLUSIONS: The impact of transmitted HIV-1 drug resistance on CD4 cell decline is time dependent, with greater rates of decline in the first year following infection. We found no evidence of a longer term effect of TDR on natural history of HIV-1 infection.

Masquelier B, Bhaskaran K, Pillay D, Gifford R, Balestre E, Jørgensen LB, Pedersen C, van der Hoek L, Prins M, Balotta C, Longo B, Kücherer C, Poggensee G, Ortiz M, de Mendoza C, Gill J, Fleury H, Porter K, Anonymous00292. · Département de Virologie et Immunologie Biologique, CHU Bordeaux, France. · J Acquir Immune Defic Syndr. · Pubmed #16284524 No free full text.

Abstract: OBJECTIVES: To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. METHODS: The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.

Pao D, Andrady U, Clarke J, Dean G, Drake S, Fisher M, Green T, Kumar S, Murphy M, Tang A, Taylor S, White D, Underhill G, Pillay D, Cane P. · Royal Sussex County Hospital, Brighton, United Kingdom. · J Acquir Immune Defic Syndr. · Pubmed #15577410 No free full text.

Abstract: Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.

Bhaskaran K, Pillay D, Walker AS, Fisher M, Hawkins D, Gilson R, McLean K, Porter K, Anonymous00258. · Medical Research Council Clinical Trials Unit, London, UK. · AIDS. · Pubmed #15199326 No free full text.

Abstract: Using data from the UK Register of HIV Sero-converters, we compared the rate of CD4 cell decline in antiretroviral-naive individuals with and without evidence of transmitted drug resistance (TDR). Although there was a suggestion that CD4 cell decline in the first year after seroconversion was faster in those with TDR,there was no evidence of a difference in the rate of decline thereafter. The virological and host determinants of this possible phenomenon are worth further exploration.