Naively changing HAART

Background

Few UK studies have systematically investigated which antiretroviral therapy (ART) combinations HIV‐infected people are commenced on, when they start and reasons for stopping or changing their regimens.

Objective

To describe when HIV‐infected ART‐naive patients started first‐, second‐ or third‐line triple ART, classes of drugs prescribed and whether stopping ART was associated with virological, immunological or clinical indicators of treatment failure.

Design

A multicentre prospective open cohort study, employing the National Prospective Monitoring System on the use, cost and outcome of HIV service provision in UK hospitals‐HIV Health‐economics Collaboration (NPMS‐HHC).

Setting

Five hundred and eighty‐five ART‐naive patients seen in one London and two non‐London HIV clinics between 1 January 1998 and 31 December 1999.

Results

Of 4044 HIV‐infected individuals seen, 585 (15%) were ART naive. Median time interval (interquartile range, IQR) between HIV diagnosis and starting triple ART was 800 (63–2094) days. Median CD4 count when first diagnosed with HIV infection was 278 (IQR 127–481) cells/µL which dropped to 190 (IQR 86–297) cells/µL when starting triple ART. Of these 585 patients, 162 started second‐line and 46 third‐line ART during the study period. Of those patients who stopped ART, 51% did not have evidence of virological, immunological or clinical indicators of therapy failure.

Conclusions

Reasons for the delay between diagnosis of HIV infection and starting ART are varied. The large proportion of individuals who stopped ART for reasons other than virological, immunological or clinical indicators of therapy failure, are most likely due to drug‐associated toxicity. Both of these findings need to be elucidated in greater detail through prospective studies.

     

The importance of serum lipoprotein (a) as an independent risk factor for premature coronary artery disease in middle-aged black and white women from the United States

Abstract. Dahlén GH, Srinivasan SR, Stenlund H, Wattigney WA, Wall S, Berenson GS (Umeå University Hospital and University of Umeå, Umeå, Sweden; and Tulane School of Public Health and Tropical Medicine, New Orleans, LO, USA). The importance of serum lipoprotein (a) as an independent risk factor for premature coronary artery disease in middle-aged black and white women from the United States. J Intern Med 1998; 244 : 417–24.

Objective

To determine the association of serum levels of lipoprotein (a) (Lp(a)) with coronary artery disease (CAD) in relation to other risk factor variables in black and white women.

Design

Retrospective case–control study.

Setting

Community of Bogalusa, Louisiana and Cardiac Catherization Laboratory at the Medical Center of Louisiana, New Orleans, USA.

Subjects

The study included 47 female cases (52% black; mean ± SD age: 50.8 ± 6.3 years) with confirmed myocardial infarction (MI) or at least 75% blockage of one or more major epicardial coronary arteries determined by angiography, and 55 controls (60% black; mean ± SD age: 49.6 ± 7.9 years) with no high grade obstructive lesion (<50% blockage) and no history of CAD.

Main outcome measures

Lipoprotein variables, homocysteine, body mass index and cigarette smoking.

Results

In the whole group, mean values of Lp(a), total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB) and very-low-density lipoprotein cholesterol (VLDL-C) were higher (P < 0.05–0.001) and apoA-I was lower (P < 0.05) in cases than in controls. The multivariate logistic regression analysis showed elevated levels of Lp(a) (>500 mg L^?1) and LDL-C (>3.36 mmol L^?1) as strong independent risk factors, with odds ratios (with 95% confidence intervals) of 13.6 (4.00–46.30) and 4.64 (1.31–16.49), respectively. ApoA-I, with an odds ratio of 0.11 (0.02—0.64), was a protective factor only at high levels (>53.6 μmol L^?1). Between races, significant odds ratios were noted in the black women for Lp(a) (OR = 15.98; P < 0.01) and LDL-C (OR = 7.69; P < 0.05) and in the white women for only Lp(a) (OR = 15.23; P < 0.01).

Conclusions

Lp(a) is an important risk factor for CAD both in black and in white women.

     

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

Objective

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.

Methods

All patients under follow‐up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow‐up, were used to identify which patients should be receiving HAART according to the guidelines.

Results

One thousand two hundred and sixty‐four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/µL and over 80% had previously had a viral load above 4 log₁₀ HIV‐1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty‐five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it.

Conclusion

Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

     

PENTA guidelines for the use of antiretroviral therapy in paediatric HIV infection. Pediatric European Network for Treatment of AIDS

Objective

To produce European Guidelines for the use of antiretroviral therapy (ART) in HIV‐infected children.

Design

Systematic literature review using Medline, the major antiretroviral conference reports, and IDSA recommendations on guideline production.

Setting

Pediatric European Network for Treatment of AIDS (PENTA) Steering Committee.

Outcome measure

Guidelines have been produced for the use of antiretroviral therapy in HIV‐infected children in Europe. Recommendations on when to start ART and which ART to start, with dosages and a summary of the relevant literature, have been produced.

Conclusions

These guidelines are aimed at assisting paediatricians in Europe with ART prescribing, and provide a more cautious approach to starting therapy than current paediatric USA guidelines.

     

Cardiovascular disease risk factors and antiretroviral therapy in an HIV-positive UK population

Aim

Although the benefits of antiretroviral therapy (ART) have been dramatic, studies have started to report a variety of drug‐related side effects and toxicities. We sought to characterize the risk factors for cardiovascular disease present in an HIV‐positive population.

Methods

A total of 394 HIV‐positive ambulant patients attending the Royal Free Hospital, London, were asked to complete a questionnaire. Questions focused on smoking habits and general health.

Results

In total, 34% of patients were aged >40 years, 29% had a family history of heart disease, 3% had diabetes, 14% suffered from raised blood pressure, 20% had a body mass index (BMI)>26 kg/m³, 7% had an alcohol consumption above the recommended UK limit, and 18% had total cholesterol levels >6.3 mmol/L. The rate of smoking observed (45%) was much higher than that observed amongst the general population in the British Health Survey for England (34%). There were significant differences between those receiving and not receiving ART. Those on ART tended to be younger (P<0.0001) and less likely to smoke cigarettes (P=0.06) or have an alcohol consumption above the recommended limit (P=0.08), but were more likely to have diabetes (P=0.05). More patients receiving ART reported, and so perceived themselves to have, raised blood fats (P<0.0001). This was confirmed when considering blood lipid levels, where those on ART had significantly raised total cholesterol levels compared to those not currently receiving ART (P<0.0001).

Conclusion

We have demonstrated an excess of cardiovascular risk factors in this cohort. These issues must be addressed if we wish to maintain the benefit of treating HIV infection.

     

Racial differences in social network experience and perceptions of benefit of arthritis treatments among New York City Medicare beneficiaries with self‐reported hip and knee pain

Objective

To determine whether social network experience and perceptions of benefit of arthritis treatments influence the decision to seek diagnosis and treatment.

Methods

A population‐based telephone survey of 515 black and 455 white Medicare beneficiaries was conducted. Validated questionnaires adapted for use in a telephone interview were used to identify people with self‐reported symptoms of hip or knee pain. Treatment history for arthritis‐related pain and perceptions of benefit of treatment were also assessed.

Results

Forty‐two percent of blacks and 31% of whites reported hip or knee pain. Forty‐two percent of blacks and 65% of whites reported knowing someone who had surgery for hip or knee pain (P < 0.0001). Blacks were less likely than whites to report that surgery had helped someone they knew with hip or knee pain (not significant).

Conclusion

Blacks know fewer people who have had surgical treatment of hip and knee pain than whites and appear to be less likely to perceive that such treatment is beneficial.

     

Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.

     

Increasing HIV transmission through male homosexual and heterosexual contact in Australia: results from an extended back‐projection approach

Objectives

The aim of the study was to reconstruct the HIV epidemic in Australia for selected populations categorized by exposure route; namely, transmission among men who have sex with men (MSM), transmission among injecting drug users (IDUs), and transmission among heterosexual men and women in Australia.

Design

Statistical back‐projection techniques were extended to reconstruct the historical HIV infection curve using surveillance data.

Methods

We developed and used a novel modified back‐projection modelling technique that makes maximal use of all available surveillance data sources in Australia, namely, (1) newly diagnosed HIV infections, (2) newly acquired HIV infections and (3) AIDS diagnoses.

Results

The analyses suggest a peak HIV incidence in Australian MSM of ∼2000 new infections per year in the late 1980s, followed by a rapid decline to a low of <500 in the early 1990s. We estimate that, by 2007, cumulatively ∼20 000 MSM were infected with HIV, of whom 13% were not diagnosed with HIV infection. Similarly, a total of ∼1050 and ∼2600 individuals were infected through sharing needles and heterosexual contact, respectively, and in 12% and 23% of these individuals, respectively, the infection remained undetected.

Discussion

Male homosexual contact accounts for the majority of new HIV infections in Australia. However, the transmission route distribution of new HIV infections has changed over time. The number of HIV infections is increasing substantially among MSM, increasing moderately in those infected via heterosexual exposure, and decreasing in IDUs.

     

Persistence of CCR5 usage among primary human immunodeficiency virus isolates of individuals receiving intermittent interleukin‐2

Objective

To investigate the impact of intermittent interleukin‐2 (IL‐2) plus combination antiretroviral therapy (cART) on HIV‐1 entry co‐receptor use.

Methods

Primary HIV‐1 isolates were obtained from 54 HIV‐1‐positive individuals at baseline and after 12 months using co‐cultivation of peripheral blood mononuclear cells (PBMC) with activated PBMC of HIV‐negative healthy donors. HIV‐1 co‐receptor use was determined on U87‐CD4 cells.

Results

Fourteen out of the 21 (67%) IL‐2‐treated individuals harbouring a primary CCR5‐dependent (R5) HIV‐1 isolate at baseline confirmed an R5 virus isolation after 12 months in contrast to 3 out of 7 (43%) of those receiving cART only. After 12 months, only 1 R5X4 HIV‐1 isolate was obtained from 21 cART+IL‐2‐treated individuals infected with an R5 virus at entry (5%) vs. 2/7 (29%) patients receiving cART alone, as confirmed by a 5‐year follow‐up on some individuals.

Conclusions

Intermittent IL‐2 administration plus cART may prevent evolution towards CXCR4 usage in individuals infected with R5 HIV‐1.

     

Trends in the epidemiology of total shoulder arthroplasty in the United States from 1990–2000

Objective

Longitudinal trends in epidemiology and utilization of total shoulder arthroplasty (TSA) have not been previously reported. We evaluated trends in the distribution of age, race, hospital volume and teaching status, outcomes, and indications for TSA during the last decade.

Methods

TSA cases (n = 12,758) were extracted from the 1990–2000 Nationwide Inpatient Sample databases. TSA trends were obtained for 3 time periods: 1990–1993 (period I), 1994–1997 (period II), and 1998–2000 (period III).

Results

Between 1990 and 2000, there were minor increases in the rate of TSA in most age groups. Ninety‐three percent of the patients undergoing TSA in all 3 time periods were white. An increased proportion of patients were operated on in high volume hospitals in period III as compared with period I. Patients discharged to inpatient rehabilitation facilities after surgery had longer lengths of in‐hospital stays as compared with those discharged home. Osteoarthritis was diagnosed in an increasing proportion of patients undergoing TSA (56.6% in period I versus 70.9% in period III).

Conclusion

There was a minor increase in the rate of TSA, and almost no change in use of TSA by nonwhites from 1990 through 2000. Efforts to understand and narrow this apparent underutilization of TSA among nonwhites are required. Further research should determine whether the observed shift of TSA to high volume centers improves surgical outcomes.

     

Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease

Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (Lund University Hospital, Sweden). Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 1998; 243 : 115–22.

Objectives

.To evaluate the impact on bone turnover of primary hyperparathyroidism (pHPT) with special reference to patients with mild pHPT, using biochemical markers of bone formation and resorption.

Design

.A longitudinal study of patients with pHPT before and one year after surgical treatment.

Setting

.The Departments of Internal Medicine and Surgery, Lund University Hospital.

Subjects

.Forty consecutive patients with pHPT. Thirty of these patients had mild pHPT and are reported separately. Data on bone mineral was also compared to a reference population.

Intervention

All patients were operated upon and restudied one year later.

Main outcome measures

.Bone resorption and formation was studied by means of the serum concentrations of the telopeptide of the carboxyterminal region of type 1 collagen (ICTP) and of alkaline phosphatase (ALP), osteocalcin and the carboxyterminal propeptide of type 1 procollagen (PICP), respectively. Bone density was measured at the distal radius by single photon absorptiometry (SPA).

Results

.Bone formation markers consistenly decreased after parathyroid surgery: ALP from 3.51 ± 0.23 to 2.94 ± 0.21 µkat L^?1 (P < 0.05), osteocalcin from 6.15 ± 0.53 to 2.89 ± 0.23 µg L^?1 (P < 0.001) and PICP from 126.4 ± 10.9 to 96.0 ± 6.5 µg L^?1 (P < 0.001). In parallel, the ICTP concentration, reflecting bone resorption, decreased from 5.10 ± 0.54 to 3.94 ± 0.34 µg L^?1 (P < 0.001). There was not any significant change in distal radius bone mineral 1 one year after surgery. In the subgroup of patients classified as mild pHPT, a significant decrease was noted for osteocalcin, PICP and for ICTP but not for ALP, without significant changes in variables reflecting distal radius bone mineral content. Glomerular filtration rate was inversely correlated to serum levels of intact PTH, ionized calcium, alkaline phosphatase, osteocalcin and ICTP and directly correlated to the 1.25-dihydroxy-vitamin D concentrations.

Conclusions

.pHPT is associated with substantial changes in circulating levels of biochemical markers of bone formation and resorption. These findings are also present in patients with mild pHPT. Renal function should be considered in the evaluation of the impact of pHPT on bone turnover.

     

Later onset of herpes zoster-associated immune reconstitution inflammatory syndrome

Objectives

The aim of the study was to determine whether immune reconstitution inflammatory syndrome (IRIS) associated with herpes zoster occurs on a different time frame from other instances of IRIS.

Methods

Statistical analysis of onset times of herpes zoster‐associated IRIS and other cases of IRIS was carried out in a retrospective cohort starting antiretroviral therapy at advanced stages of HIV infection.

Results

Herpes zoster‐associated IRIS was significantly more frequent after the first 3 months of successful highly active antiretroviral therapy (HAART), than other instances of IRIS (IRIS associated with tuberculosis, Mycobacterium avium complex, Kaposi's sarcoma, etc.) which mainly occurred during the first 3 months of treatment.

Conclusions

The characteristic onset time pattern of herpes zoster‐associated IRIS, coincident with the second phase of immune recovery under HAART, suggests that the immune recovery events underlying herpes zoster‐associated IRIS are different from those underlying other types of IRIS. Our findings may be useful in improving the follow‐up of individuals who start HAART at an advanced stage of HIV infection.

     

Effect of physical activity on functional status among older middle‐age adults with arthritis

Objective

To determine the effect of leisure time and work‐related physical activity on changes in physical functioning among 3,554 nationally representative survey respondents, ages 53–63 years in 1994, with arthritis and joint symptoms, interviewed in the Health and Retirement Study (HRS).

Methods

In 1992–1994, light and vigorous exercise items were empirically categorized into recommended, insufficient, and inactive leisure time physical activity levels using data from the HRS. Leisure and work‐related physical activity levels in 1994 were used to predict 1996 functional decline or improvement, controlling for baseline functional difficulties, health status, sociodemographic characteristics, and behavioral risk factors.

Results

Whereas 29.7% of respondents reported functional declines in 1996, 38.6% of those with baseline difficulties in 1994 reported improvement. Compared with inactive respondents, recommended and insufficient leisure time physical activity were equally protective against functional decline (odds ratio [OR] 0.59 and 0.62, respectively; P < 0.0001). Higher levels of physical activity were also modestly associated with functional improvement among respondents with baseline functional difficulties (OR 1.47, P = 0.05 and OR 1.45, P = 0.01, respectively). Work‐related physical activity was not a significant predictor of decline or improvement.

Conclusion

Given the high prevalence of arthritis, even modest increases in rates of lifestyle physical activity among older adults could make a substantial contribution to disability‐free life expectancy.

     

Impact of transmission of drug-resistant HIV on the course of infection and the treatment success. Data from the German HIV-1 Seroconverter Study

Background

Data on the clinical course of infection in patients with transmitted drug‐resistant HIV before and after initiation of treatment are scarce.

Patients and methods

Genotypic resistance was analysed in 504 therapy‐naïve individuals with a known date of infection. Resistance was predicted using the Stanford algorithm. Clinical parameters for 80 individuals with transmitted drug‐resistant HIV and for 424 patients with susceptible virus were analysed.

Results

In 16% of the individuals transmitted drug‐resistant HIV was found. Detection of drug‐resistant HIV was more likely in individuals with acute primary HIV infection [odds ratio (OR)=1.529; 95% confidence interval (95% CI) 1.001; 2.236]. At the time of infection patients with an acute infection with resistant HIV had lower viral loads. CD4 cell counts tended to be higher and the CD4 cell loss more pronounced in the group with resistant HIV. Suppression of the viral load below the detection limit was achieved in 64% of the group with resistant HIV and in 85% of the group with susceptible HIV 6 months after initiation of therapy (P=0.199). The majority of the group with resistant HIV (74%) received at least one compromised drug.

Conclusion

First‐line treatment including drugs with predicted resistance can impair virological success in some patients. Factors influencing the decision to include compromised drugs need to be investigated.

     

Changes in lean body mass and total body weight are weakly associated with physical functioning in patients with HIV infection

Context

For clinicians managing weight loss in patients with HIV, it would be useful to understand how changes in lean body mass (LBM) effect physical functioning, and whether LBM is more strongly related to physical functioning than total body weight (TBW).

Objective

To determine the relationship of changes in LBM and changes in total body weight (TBW) to changes in self‐reported physical functioning in men and women with HIV infection.

Methods

Study design was longitudinal analysis of 1474 patient‐intervals (each interval was approximately 6 months long) in 486 persons. Patients were participants in Nutrition for Healthy Living, a cohort study of HIV positive persons in Massachusetts and Rhode Island. The main outcome measure was change in self‐reported physical functioning.

Results

Of the 1474 intervals, 1165 were contributed by men and 309 by women. The mean CD4 count for the 1474 intervals was 383 cells/µL. In men, 5 kg changes in LBM and TBW were associated with 2.2 (95% confidence interval, 0.9, 3.4, P= 0.001) and 2.6 (95% confidence interval, 1.3, 3.9, P= 0.0002) point changes in physical functioning (on a 100‐point scale), respectively, after adjusting for covariates. The relationships of changes in LBM and TBW to changes in physical functioning were linear. In women, there were no significant relationships between changes in LBM or TBW to changes in physical functioning.

Conclusions

In this longitudinal analysis of relatively healthy persons with HIV infection, changes in LBM and TBW were significantly related to changes in physical functioning in men, but the magnitude of the relationship was small. In women, changes in LBM and TBW were not related to changes in physical functioning. Our data suggest that it is not necessary to measure body composition (lean and fat compartments) to understand the impact of changes in weight on physical functioning – it is sufficient to follow total body weight.

     

The HLA–B*5703 allele confers susceptibility to the development of spondylarthropathies in Zambian human immunodeficiency virus–infected patients with slow progression to acquired immunodeficiency syndrome

Objective

To analyze the HLA distribution in a population of individuals from Zambia in order to establish a possible relationship between the progression of human immunodeficiency virus (HIV) infection and the development of spondylarthropathy (SpA).

Methods

A large epidemiologic analysis of rheumatology patients living in Zambia was performed in order to identify those who had SpA. We selected 64 patients with SpA and found that 54 also had HIV type 1 (HIV‐1) infection; only 10 were HIV negative. Additionally, we selected 57 HIV‐infected individuals without SpA and 43 healthy controls. Among all of the HIV‐1–infected patients, 25 SpA‐positive and 24 SpA‐negative patients were classified as slow progressors to acquired immunodeficiency syndrome (AIDS), and 8 SpA‐positive and 26 SpA‐negative patients were classified as rapid progressors. All patients were typed for HLA–B alleles.

Results

Of the 64 patients with SpA, HIV infection was observed in 54 (84%). The frequency of B*5703 was increased in patients who were SpA positive and HIV positive compared with patients who were SpA negative and HIV positive (P = 0.0002, odds ratio [OR] 8.28). Among patients who were slow progressors to AIDS, this allele was overrepresented in those with SpA compared with those without SpA (corrected P = 0.001, OR 26.25).

Conclusion

HLA–B*5703 seems to be a protective allele against the progression of HIV infection but could influence the increased incidence of SpA observed in this population.