Articles tagged as "Comorbidity"

Low CD4 counts among alcohol-dependent people on antiretroviral therapy – not due to poor adherence

Alcohol dependence and CD4 cell count: is there a relationship?

Malbergier A, Amaral RA, Cardoso LD. AIDS Care. 2014 Sep 1:1-5. [Epub ahead of print]

Alcohol and other drugs use seem to be common among people infected with HIV on antiretroviral treatment (ART). Their effects on HIV progression is still in debate. This study aimed to assess the association between alcohol and drug use and an HIV disease progression biomarker (CD4 cell count) among patients on ART. A cross-sectional study was carried out at an HIV treatment center affiliated with Medical School of the University of Sao Paulo, Brazil. Four hundred and thirty-eight HIV-positive patients on ART were interviewed by trained psychiatrists and psychologists using the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Alcohol Use Disorders Identification Test (AUDIT), 17-item Hamilton Rating Scale for Depression, and the Simplified Medication Adherence Questionnaire (SMAQ). In the previous month, 219 (50%) and 41 (9.3%) patients reported use of alcohol and illicit drugs, respectively. Fifty patients (12.6%) were classified as having harmful alcohol use by AUDIT. According to SCID-I, 80 patients (18.3%) were alcohol abusers, 24 (5.5%) alcohol dependents, and 21 (4.2%) had a current depressive disorder. Almost 73% (n = 319-72.8%) of the patients were adherent to ART. Alcohol dependents were nine times (p < 0.01) more likely to have CD4 cell count ≤200/mm3, and this association was independent of ART adherence. In conclusion, alcohol dependence seems to be associated with low CD4 cell count in HIV-positive patients. Based on these data, HIV health care workers should always assess alcohol consumption in the treatment setting, and patients should be advised that alcohol dependence may be linked to low CD4.

Abstract access 

Editor’s notes: The prognosis for people living with HIV who initiate antiretroviral therapy (ART) depends not only on their adherence to ART, but also the presence of co-morbid health conditions. There is now increasing focus on the role mental health disorders have on HIV-related outcomes. In this study of 438 HIV positive people on ART in Brazil, nearly 20% of individuals were found to be abusing alcohol, and five percent were diagnosed as being alcohol dependent. The people who were alcohol dependent were nine times more likely to have CD4 count <200/mm3, an association which was independent of ART adherence, HIV viral load and illicit substance use. As the availability of mental health care in low- and middle-income countries continues to expand, people living with HIV will comprise a key population for these services. Future research must confirm whether the relationship between alcohol dependence and CD4 count persists over time, and how alcohol dependence services can be integrated with HIV care services.

Latin America
Brazil
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Prednisolone does not reduce poor outcomes in TB pericarditis

Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

Mayosi BM, Ntsekhe M, Bosch J, Pandie S, Jung H, Gumedze F, Pogue J, Thabane L, Smieja M, Francis V, Joldersma L, Thomas KM, Thomas B, Awotedu AA, Magula NP, Naidoo DP, Damasceno A, Chitsa Banda A, Brown B, Manga P, Kirenga B, Mondo C, Mntla P, Tsitsi JM, Peters F, Essop MR, Russell JB, Hakim J, Matenga J, Barasa AF, Sani MU, Olunuga T, Ogah O, Ansa V, Aje A, Danbauchi S, Ojji D, Yusuf S; IMPI Trial Investigators. N Engl J Med. 2014 Sep 18;371(12):1121-30. doi: 10.1056/NEJMoa1407380. Epub 2014 Sep 1.

Background: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis.

Methods: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.

Results: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer.

Conclusions: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.

Abstract  Full-text [free] access

Editor’s notes: Tuberculous pericarditis remains an important and serious complication of HIV disease. Previous studies have suggested that treatment with steroids, in addition to standard TB treatment, reduces the risk of serious complications such as constrictive pericarditis. However, previous studies have been small, and have included few HIV-positive people.

This randomised controlled trial across eight countries in Africa tested two treatments for people with either definite or probable TB pericarditis. These included high dose steroid treatment, and injections of Mycobacterium indicus pranii. Mycobacterium indicus pranii is an environmental mycobacterium suggested to have a possible effect to reduce inflammation among people with TB. Two-thirds of the 1400 study participants were HIV-positive, most of whom were not taking antiretroviral therapy at the time of enrolment. The median CD4 count at enrolment was around 150 cells/µl. The primary outcome of the study was a composite of death, cardiac tamponade requiring drainage, and constrictive pericarditis. 

The death rate overall was high at 18%, and the main causes of death were considered to be pericarditis, TB, and HIV disease. Immunotherapy with Mycobacterium indicus pranii had no beneficial effects on any outcome. There was no overall difference in the composite primary outcome among people receiving prednisolone compared to placebo. However, people receiving prednisolone were less likely to develop constrictive pericarditis or to be hospitalised. There were more cancers (primarily Kaposi’s sarcoma among HIV-positive people) in people receiving either prednisolone or Mycobacterium indicus pranii, although the absolute rate was low. This is in keeping with previous observations.

Limitations of the study include that most people did not have microbiological confirmation of their TB diagnosis, so could potentially have had other causes of pericarditis for which prednisolone would not be expected to improve outcomes.

The results of this trial suggest that guidelines concerning use of prednisolone for TB pericarditis should be reviewed, particularly for people living with HIV. The poor outcomes among this group of people with TB and advanced HIV disease highlight the need for earlier HIV diagnosis, initiation of antiretroviral therapy, and TB preventive therapy.

Avoid TB deaths
Comorbidity, HIV Treatment
Africa
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Mefloquine not suitable as intermittent preventive treatment of malaria, in pregnant women living with HIV

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial.

Gonzalez R, Desai M, Macete E, Ouma P, Kakolwa MA, Abdulla S, Aponte JJ, Bulo H, Kabanywanyi AM, Katana A, Maculuve S, Mayor A, Nhacolo A, Otieno K, Pahlavan G, Ruperez M, Sevene E, Slutsker L, Vala A, Williamsom J, Menendez C. PLoS Med. 2014 Sep 23;11(9):e1001735. doi: 10.1371/journal.pmed.1001735. eCollection 2014.

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).

Methods and findings: A total of 1071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.

Conclusions: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.

Abstract  Full-text [free] access

Editor’s notes: The gold standard for intermittent preventive treatment of malaria in pregnancy (IPTp) is at least three doses of sulfadoxine-pyrimethamine, along with the use of insecticide-treated nets. In resource-limited, high HIV prevalent areas, all HIV-positive pregnant women are recommended to take co-trimoxazole prophylaxis. This rules out the concomitant use of sulfadoxine-pyrimethamine because of the increased risk of drug toxicity. However, the effectiveness of co-trimoxazole alone to prevent malaria in pregnant women living with HIV has not been established.   

This article reports a randomised double-blind placebo-controlled trial. The trial compares the efficacy of three-monthly doses of mefloquine (a long-acting efficacious antimalarial, considered to be safe throughout pregnancy) with placebo, in pregnant women living with HIV taking daily co-trimoxazole. Women in the mefloquine arm had a reduced risk of maternal malarial parasitaemia, a reduced rate of placental malaria and reduced incidence of non-obstetric hospital admissions. However, mefloquine was poorly tolerated. Unexpectedly, women in the mefloquine arm had a higher HIV viral load at delivery and were more likely to transmit HIV to their child. Since this finding was based on an exploratory, rather than a pre-planned analysis, its validity is uncertain. If other data support this finding, a better understanding of the underlying mechanism (biological/immunological) will be important to inform future alternative drug regimens for pregnant women living with HIV. 

This trial suggests that an effective antimalarial drug combined with co-trimoxazole can offer additional protection against malaria in pregnant women living with HIV, but mefloquine is not the drug of choice for this purpose. 

Avoid TB deaths
Africa
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Cotrimoxazole appears safe in pregnant women living with HIV, despite poor quality evidence

Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis.

Ford N, Shubber Z, Jao J, Abrams EJ, Frigati L, Mofenson L. J Acquir Immune Defic Syndr. 2014 Aug 15;66(5):512-21. doi: 10.1097/QAI.0000000000000211.

Introduction: Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy.

Methods: Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.

Results: Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4 196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; τ² = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low.

Conclusions: The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.

Abstract access 

Editor’s notes: Cotrimoxazole significantly reduces morbidity and increases survival in people living with HIV (including people on antiretroviral therapy) in resource-limited settings.  However, there is some concern of potential human foetal risk when cotrimoxazole is taken during pregnancy. This systematic review found very limited evaluable data on maternal and infant outcomes associated with cotrimoxazole exposure during pregnancy. Cotrimoxazole is likely to be of most benefit in high HIV burden, low-income settings. In this context, the known benefit of treatment outweighs the potential risk to the foetus, in HIV-positive pregnant women.  Importantly, this paper highlights the need for better pregnancy outcome surveillance in women living with HIV, in resource-poor settings, which includes evaluation of exposure to cotrimoxazole and antiretroviral treatment.  

Africa, Asia, Europe, Northern America, Oceania
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Causes of death among people with tuberculosis and low CD4 counts

Causes and determinants of mortality in HIV-infected adults with tuberculosis: an analysis from the CAMELIA ANRS 1295-CIPRA KH001 randomized trial.

Marcy O, Laureillard D, Madec Y, Chan S, Mayaud C, Borand L, Prak N, Kim C, Lak KK, Hak C, Dim B, Sok T, Delfraissy JF, Goldfeld AE, Blanc FX, CAMELIA (ANRS 1295-CIPRA KH001) Study Team.  Clin Infect Dis. 2014 Aug;59(3):435-45. doi: 10.1093/cid/ciu283. Epub 2014 Apr 23.

Background:  Shortening the interval between antituberculosis treatment onset and initiation of antiretroviral therapy (ART) reduces mortality in severely immunocompromised human immunodeficiency virus (HIV)-infected patients with tuberculosis. A better understanding of causes and determinants of death may lead to new strategies to further enhance survival.

Methods: We assessed mortality rates, causes of death, and factors of mortality in Cambodian HIV-infected adults with CD4 count ≤200 cells/µL and tuberculosis, randomized to initiate ART either 2 weeks (early ART) or 8 weeks (late ART) after tuberculosis treatment onset in the CAMELIA clinical trial.

Results: Six hundred sixty-one patients enrolled contributed to 1 366.1 person-years of follow-up; 149 (22.5%) died. There were 8.3 deaths per 100 person-years (95% confidence interval [CI], 6.4-10.7) in the early-ART group and 13.8 deaths per 100 person-years (95% CI, 11.2-16.9) in the late-ART group (P = .002). Tuberculosis was the primary cause of death (28%), followed by other HIV-associated conditions (19%). Factors independently associated with mortality in the first 26 weeks were the age, body mass index, hemoglobin, interrupted or ineffective tuberculosis treatment before identification of drug resistance, disseminated tuberculosis, and nontuberculous mycobacterial disease. After 50 weeks in the trial, the most frequent causes of death were non-HIV related or tuberculosis related, including drug toxicity; factors associated with mortality were late ART, loss to follow-up, and absence of cotrimoxazole prophylaxis.

Conclusions: Despite ART introduction, mortality remained high, with tuberculosis as the leading cause of death. Reducing tuberculosis-related mortality remains a challenge in resource-limited settings and requires innovative strategies.

Abstract access 

Editor’s notes: Tuberculosis (TB) remains the most important cause of death among HIV-positive people worldwide, despite increasing access to antiretroviral therapy. There is a strong emphasis on reducing TB mortality as part of the post-2015 global TB strategy. This makes it even more important to define causes of death, so that appropriate programmes can be introduced.

This analysis in Cambodia, reports causes of death among HIV-positive people with sputum smear-positive TB, and CD4 counts below 200. The participants took part in a trial of antiretroviral therapy started early, i.e. two weeks after start of TB treatment, versus late, eight weeks after TB treatment start. Causes of death were assigned by site investigators and validated by review of medical records by investigators who had not been involved in the patient’s care. Tuberculosis was the most frequently assigned cause of death (42 of 149 deaths). HIV-associated conditions accounted for 28 deaths of which diarrhoea, non-tuberculous mycobacterial disease and immune reconstitution syndrome were the most frequent. For 23 deaths, TB and HIV-associated conditions were considered equally likely. This highlights the difficulty in distinguishing between these two causes of death among people with advanced HIV-related immunosuppression. Limited autopsies based on multiple biopsies are far more acceptable to families than traditional full autopsy, and could be used to identify causes of death with greater accuracy. Further it was notable that cotrimoxazole prophylaxis was associated with a lower risk of death after 50 weeks of follow-up, underlining the importance of this programme.  

Avoid TB deaths
Comorbidity
Asia
Cambodia
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Model estimates large global burden of childhood tuberculosis infection and potentially preventable future tuberculosis disease

Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.

Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Lancet Glob Health. 2014 Aug;2(8):e453-9. doi: 10.1016/S2214-109X(14)70245-1. Epub 2014 Jul 8.

Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.

Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.

Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15 319 701 (IQR 13 766 297-17 061 821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7 591 759 (5 800 053-9 969 780), and 650 977 children (424 871-983 118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53 234 854 (41 111 669-68 959 804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.

Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.

Abstract  Full-text [free] access 

Editor’s notes: Estimating the burden of childhood tuberculosis has been largely neglected until recently. Children with tuberculosis rarely transmit and therefore from a control perspective, childhood tuberculosis does not notably contribute to the continuation of the tuberculosis epidemic. This modelling paper attempts to estimate the global burden of childhood tuberculosis infection and disease. Incidence estimates are made by using adult tuberculosis prevalence data to tackle the known limitations of using paediatric notification data. A second model estimates the prevalence of infection in children and household exposure, ignoring exposure outside of the household.  As with all mathematical model predictions, precision of estimates are dependent on the data used as inputs in the model. Despite these limitations, the paper draws attention to the fact that the burden of childhood tuberculosis infection and disease is significant and reflects failure of tuberculosis control in the 22 high-burden countries. The paper also highlights the fact that household contact tracing and preventive therapy in tuberculosis-exposed children could substantially reduce future tuberculosis-related morbidity.

Avoid TB deaths
Comorbidity, Epidemiology
Africa, Asia, Latin America
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Water filters reduce diarrhoea among people with HIV

Water filter provision and home-based filter reinforcement reduce diarrhea in Kenyan HIV-infected adults and their household members.

Pavlinac PB, Naulikha JM, Chaba L, Kimani N, Sangare LR, Yuhas K, Singa BO, John-Stewart G, Walson JL. Am J Trop Med Hyg. 2014 Aug 6;91(2):273-80. doi: 10.4269/ajtmh.13-0552. Epub 2014 May 19.

Among human immunodeficiency virus (HIV)-infected adults and children in Africa, diarrheal disease remains a major cause of morbidity and mortality. We evaluated the effectiveness of provision and home-based reinforcement of a point-of-use water filtration device to reduce diarrhea among 361 HIV-infected adults in western Kenya by comparing prevalence of self-reported diarrhea before and after these interventions. After provision of the filter, 8.7% of participants reported diarrhea compared with 17.2% in the 3 months before filter provision (odds ratio [OR] = 0.39, 95% confidence interval [95% CI] = 0.23-0.66, P < 0.001). The association was similar among 231 participants who were already taking daily cotrimoxazole prophylaxis before being given a filter (OR = 0.47, 95% CI = 0.25-0.88, P = 0.019). Educational reinforcement was also associated with a modest reduction in self-reported diarrhea (OR = 0.50, 95% CI = 0.20-0.99, P = 0.047). Provision and reinforcement of water filters may confer significant benefit in reducing diarrhea among HIV-infected persons, even when cotrimoxazole prophylaxis is already being used.

Abstract access 

Editor’s notes: Diarrhoeal disease remains an important cause of morbidity among HIV-positive people. This analysis was part of a larger study of HIV-positive adults who were not taking antiretroviral therapy. The frequency of diarrhoea, measured by self-report, was compared before and after participants were given a water filtration device. After receiving the device, fewer people reported diarrhoea, with an odds ratio of 0.39. The beneficial effect was similar among people who were already taking cotrimoxazole prophylaxis. The benefits of water filtration or chlorination have been shown in previous studies, but this is a useful reminder of the value of clean water programmes in reducing diarrhoeal disease.  

Avoid TB deaths
Comorbidity
Africa
Kenya
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Facing uncertainty – ageing with HIV

Aging with HIV: a model of disability.

Solomon P, O'Brien K, Wilkins S, Gervais N. J Int Assoc Provid AIDS Care. 2014 Aug 22. pii: 2325957414547431. [Epub ahead of print]

The purpose of this qualitative study was to develop a theoretical model describing the disability experienced by older adults living with HIV. Forty nine HIV positive men and women over the age of 50 years participated in in-depth qualitative interviews. Transcribed interviews were analyzed using grounded theory techniques. Uncertainty or worrying about the future was at the core of the model. Components of disability including symptoms and impairments, difficulties with day to day activities and challenges to social participation were experienced in the context of extrinsic or environmental factors (social support, stigma) and intrinsic contextual factors (positive living strategies, age). Time was an overarching component of the model. The model suggests areas for interventions to prevent or reduce disability related to the consequences of aging with HIV and improve overall quality of life.

 Abstract access 

Editor’s notes: This paper is a very welcome addition to the growing body of research on HIV and ageing. Time is highlighted in the findings. Time has been regained (because treatment has kept people alive to grow old) and time is moving too fast (as individuals fear accelerated ageing because of HIV). The authors also highlight the centrality of uncertainty in the lives of the 49 people interviewed. Uncertainty is central to ageing. No-one of us knows quite how well we may remain as we age. However, the interaction between HIV and the ageing process is an added layer of uncertainty. The average age of people in this study was only 56, so they were relatively young, older people. We can expect worries over adequate social support and managing increasing ill-health and disability, will increase as people age. The authors urge us to look at the impact of HIV on older people’s quality of life as a whole, in the design of programmes. This paper is a timely reminder of the social, mental and physical burden HIV continues to impose on people’s lives.

Northern America
Canada
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Falling death rates among people in HIV care: AIDS remains common, non-AIDS cancers need attention

Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration.

Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte A, Phillips AN, Sabin CA, Lundgren JD, D:A:D Study Group. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.

Background: With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011.

Methods: Individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D:A:D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D:A:D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression.

Findings: 3 909 of the 49 731 D:A:D study participants died during the 308 719 person-years of follow-up (crude incidence mortality rate, 12.7 per 1 000 person-years [95% CI 12.3-13.1]). Leading underlying causes were: AIDS-related (1 123 [29%] deaths), non-AIDS-defining cancers (590 [15%] deaths), liver disease (515 [13%] deaths), and cardiovascular disease (436 [11%] deaths). Rates of all-cause death per 1 000 person-years decreased from 17.5 in 1999-2000 to 9.1 in 2009-11; we saw similar decreases in death rates per 1 000 person-years over the same period for AIDS-related deaths (5.9 to 2.0), deaths from liver disease (2.7 to 0.9), and cardiovascular disease deaths (1.8 to 0.9). However, non-AIDS cancers increased slightly from 1.6 per 1 000 person-years in 1999-2000 to 2.1 in 2009-11 (p=0.58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009-11 vs 1999-2000: 0.92 [0.70-1.22]). However, all-cause (0.72 [0.61-0.83]), liver disease (0.48 [0.32-0.74]), and cardiovascular disease (0.33 [0.20-0.53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999-2000 and 141/627 [22%] in 2009-11) and liver-related (40/256 [16%] in 1999-2000 and 64/627 [10%] in 2009-11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999-2000 to 142/627 [23%] in 2009-11).

Interpretation: Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement.

Abstract access

Editor’s notes: Causes of death among people with HIV help to identify priorities for HIV care services. This very large cohort study, including nearly 50 000 HIV-positive people in industrialised country clinics, reports on changes in causes of death since 1999. Effective antiretroviral treatment was widely available for this cohort. All-cause mortality decreased over time, partly explained by effective antiretroviral therapy and increased CD4 cell counts. Death rates due to AIDS declined over time. However, even in 2009-11, AIDS remained a leading cause of death, suggesting that further efforts to diagnose and treat people with HIV earlier are required.

Deaths due to cardiovascular and liver-related causes decreased over time, even after adjustment for other potentially contributing factors. This suggests that people in this cohort were benefitting not only from good management of their HIV disease, but also from other preventive programmes for cardiovascular and other risk factors. By contrast, death rates due to non-AIDS-related cancers have not fallen, suggesting that more attention to prevention and early detection of common malignancies is needed.

Comorbidity, Epidemiology
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Converging epidemics of HIV and hypertension in Africa

Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study.

Peck RN, Shedafa R, Kalluvya S, Downs JA, Todd J, Suthanthiran M, Fitzgerald DW, Kataraihya JB. BMC Med. 2014 Jul 29;12(1):125. [Epub ahead of print]

Background: The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity.

Methods: In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher’s exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding.

Results: Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P=0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR)= 2.19 (1.18 to 4.05), P=0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P= 0.003) and a lower odds of hypertension after adjustment (OR 0.35 (0.15 to 0.84), P= 0.02 in the best model). Awareness of hypertension was 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with hypertension (P <0.001 for trend); among hypertensive participants, 50/76 (65.8%) had microalbuminuria and 20/76 (26.3%) had an estimated glomerular filtration rate (eGFR) <60 versus 33/184 (17.9%) and 16/184 (8.7%) participants with normal blood pressure.

Conclusions: HIV-infected adults on ART >2 years had two-fold greater odds of hypertension than HIV-negative controls. HIV-infected adults with hypertension were rarely aware of their diagnosis but often have evidence of kidney disease. Intensive hypertension screening and education are needed in HIV-clinics in sub-Saharan Africa. Further studies should determine if chronic, dysregulated inflammation may accelerate hypertension in this population.

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Editor’s notes: The prevalence of both hypertension and HIV in sub-Saharan Africa is the highest among any region in the world. Hypertension is a leading risk factor for disease and accounts for nearly 10 million deaths a year. As antiretroviral therapy (ART) coverage has increased, infection-related mortality rates have substantially declined. Increased life-expectancy and weight gain among people taking ART may “unmask” an epidemic of hypertension in sub-Saharan Africa, where, unlike other global regions, the blood pressure of adults continues to rise.

This study showed a high prevalence of hypertension among HIV-positive adults taking ART for two or more years. The prevalence was nearly double that among HIV-negative adults, even after adjusting for age, sex and adiposity. In contrast, the prevalence of hypertension among ART-naïve adults was significantly lower than that among HIV-negative adults. There was no association between use of the first line antiretroviral drugs and hypertension, suggesting that the high prevalence of drugs cannot be explained by the type of drugs used to treat HIV infection.

Of concern, only 25% of hypertensive adults were aware of their condition. Among HIV-positive adults on ART, some 75% of those with hypertension were undiagnosed, some 85% were untreated and more than 95% were uncontrolled. Importantly, hypertension was strongly associated with kidney disease. Given that this is a cross-sectional study, it is not clear whether hypertension preceded kidney disease or vice versa.

Given the high prevalence of hypertension among HIV-positive peoples and that HIV is now a treatable, chronic condition, HIV care provides an opportunity for management of hypertension and should be considered as an integral aspect of HIV care. Studies are needed to understand the role of HIV and ART in causing hypertension, so that appropriate management strategies can be developed.

Comorbidity, HIV Treatment
Africa
United Republic of Tanzania
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