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Introduction: Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease., Methods: In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy., Results: We followed-up 136 HIV positive and 73 HIV negative participants for 12 months with weekly documentation of any new respiratory symptoms. We found that HIV status did not affect the frequency of acute respiratory illness: unadjusted incidence rates per person year of follow-up were 2.08 illnesses (95% CI 1.81-2.38) and 2.30 illnesses (1.94-2.70) in HIV positive and negative participants respectively, IRR 0.87 (0.70-1.07) p = 0.18. However, when acute respiratory illnesses occurred, PLW-HIV reported more severe symptoms (relative fold-change in symptom score 1.61 (1.28-2.02), p <0.001) and were more likely to seek healthcare advice (42% vs 18% of illnesses, odds ratio 3.32 (1.48-7.39), p = 0.003). After adjustment for differences in baseline characteristics, PLW-HIV still had higher symptom scores when unwell., Conclusions: HIV suppression with antiretroviral therapy reduces the frequency of acute respiratory illness to background levels, however when these occur, they are associated with more severe self-reported symptoms and greater healthcare utilisation. Exploration of the reasons for this greater severity of acute respiratory illness may allow targeted interventions to improve the health of people living with HIV., Trial Registration: ISRCTN registry (ISRCTN38386321)., Competing Interests: The authors have declared that no competing interests exist.

Objective: To study the rate of treatment change due to toxicities in patients who achieved viral suppression within 6 months of starting antiretroviral therapy and who have never experienced virological failure., Methods: Included patients attended the Royal Free Hospital in London, started antiretroviral therapy in 2000-2005, and achieved viral suppression within 6 months. Included follow-up (censored at virological failure) was spent on a regimen of lamivudine or emtricitabine, with a second nucleoside/nucleotide reverse transcriptase inhibitor, and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor., Results: In 912 person-years, there were 140 treatment changes due to toxicities (rate = 15.4 per 100 person-years, confidence interval = 12.8-17.9). In the multivariable analysis, factors associated with a higher rate of treatment change due to toxicities included increased age (for every 10 years increase: incidence rate ratio = 1.28, confidence interval = 1.04-1.57), being on stavudine compared with zidovudine (incidence rate ratio = 2.04, confidence interval = 1.28-3.26), and being on lopinavir compared with efavirenz (incidence rate ratio = 1.55, confidence interval = 1.04-2.31), whereas factors associated with a lower rate were being on tenofovir compared with zidovudine (incidence rate ratio = 0.46, confidence interval = 0.29-0.73), and being on atazanavir compared with efavirenz (incidence rate ratio = 0.23, confidence interval = 0.06-0.91)., Conclusions: In patients who have never experienced virological failure, the rate of treatment change due to toxicities is low, and certain regimens are associated with an even lower rate of change. If virological failure is avoided, some regimens are so far proving to be sufficiently stable to suggest that very long-term use is potentially feasible.

Objectives: To describe the characteristics of deaths that occur among HIV-positive individuals in the HAART era., Design: Observational database., Methods: Deaths were reviewed that occurred among HIV-positive individuals seen at the Royal Free Hospital, London between January 1998 and December 2003., Results: Over the study period, there were 121 deaths; death rates declined from approximately 2.0/100 person-years of follow-up in 1998-2000 to approximately 1.0/100 person-years of follow-up in 2001-2003. Approximately one half of deaths (45.5%) were from AIDS-related causes and 74 deaths (61.2%) occurred in individuals who had received HAART: patients had been exposed to a median of seven (range 2-14) antiretroviral drugs and two-fifths had started treatment in the pre-HAART era. Another 15 patients had received only non-HAART treatment regimens prior to death. The median pre-death CD4 cell counts were 68 and 167 cells/microl among those who had and had not received HAART; 23 (31.1%) and 4 (8.5%) had HIV RNA < 400 copies/ml, respectively. Of the patients exposed to HAART for at least 6 months and who experienced viral rebound, information was available on resistance for 26 (21.5% of the total deaths) and 19 of those tested had at least one resistance mutation (median 5, range, 1-16)., Conclusions: While mortality rates among HIV-infected individuals at our centre have fallen since 1988, the deaths that do now occur are more diverse and are the result of a number of factors, including late presentation, delayed uptake of HAART and the previous use of treatment combinations that are now viewed as suboptimal.

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.