Abstract
Life expectancy of HIV patients has increased over time. Older HIV patients have a higher frequency of noncommunicable diseases (NCD) than general population, and require multiple treatments. The main objective is to evaluate the changes in frequency of NCD and polypharmacy in HIV patients of three referral centers in Salvador and São Paulo. We compared the frequency of NCD and use of concomitant treatments in HIV patients, >50 years, in three Brazilian referral centers (São Paulo and Salvador). Data on sociodemographic characteristics, HIV therapy, CD4 count and viral load measurements, and frequency of NCD at baseline and last medical visit were recorded. We evaluated 451 patients, 128 in Salvador and 323 in São Paulo. Mean age was 57.9 ± 6.9 years. Mean baseline CD4 count was 199 ± 169. At baseline, dyslipidemia (4.0%) was the most frequent comorbidity, but at last visit we detected a high frequency of diabetes (14.9%), dyslipidemia (26.7%), osteoporosis (6.7%), stroke (4.4%), and malignancies (3.1%). Use of concomitant drugs for treatment of NCD increased significantly between first and last visit, especially antihypertensive, lipids lowering, and diabetes drugs. Aging in HIV patients in Brazil is characterized by an increasing incidence of NCD and polypharmacy.
Population aging is a global phenomenon that has been intensified in recent decades, demanding that health care services be prepared to meet the specific need of such individuals. Brazil will have 34 million of elderly people by 2025. 1
A similar picture can also be observed in people living with HIV (PLHIV). The increased survival of the PVHIV and the proportion of individuals who have already been diagnosed in a more advanced age explains the increase in the number of reported cases >50 years of age. 2 The available evidence shows that HIV-1-infected patients >50 years of age have a higher likelihood of presenting one or more noncommunicable disease (NCD) and of using multiple medicines in addition to antiretroviral drugs. 3,4 This leads to increasing pill burden, with a consequent risk of poor adherence to therapy, more adverse events, and a higher risk of drug–drug interaction. 5,6
To evaluate the characteristics of HIV patients >50 years, and the changes in their epidemiological profile, we compared the findings detected in their first medical visit and in the most recent evaluation. The observed changes in the prevalence of NCD and in number of prescribed drugs were consistent with an accelerated aging in this specific population.
We reviewed medical charts of 451 patients (>50 years), consecutively attended at three referral centers for AIDS care in Brazil: 128 at the Complexo Hospital Universitário Professor Edgard Santos (CHUPES), in Salvador, Northeastern Brazil; 195 at the Centro de Referência e Treinamento (CRT); and 128 at the AIDS outpatient Clinic of Hospital São Paulo (HSP), both services in São Paulo, Southeastern region, in 2016. We retrieved information on sociodemographic characteristics and clinical/laboratory data at patient's first medical visit and at last reported evaluation. CD4 cell count, HIV-1 RNA plasma viral load (PVL), presence of any comorbidity and use of antiretroviral drugs, as well as the number and type of other drugs used for treatment of comorbidities.
Continuous variables were reported as mean and standard deviation or median and interquartile range as appropriate. Prevalence of comorbidities was compared by Wilcoxon test. McNemar test was used to compare the mean number of drugs at first and last visits. Statistical analysis was performed by using the computer software SPSS version 20 (SPSS, Inc., Chicago, IL). Statistical tests were two sided and differences were considered statistically significant at p < .05.
The project was approved by IRB of the three sites. All included patients provided a written informed consent, before entering the study.
All patients were >50 years (median 51 years, 68% men), and only 17.9% of them reported current active work. The mean time of follow-up was 12.7 years, (5,728 patient years). The mean CD4 cells count at baseline was <200 cells/mL. Currently, 98% of patients were on combined antiretroviral therapy (c-ART), and most (87%) patients had PVL below the detection limit (<50 copies/mL), 95% of them had a PVL <400 copies/mL. Table 1 shows patients' baseline characteristics.
Characteristics of HIV Patients >50 Years in Three Brazilian Referral Centers
p < .05 for comparison between groups.
p < .001 for all comparisons.
CRT, Centro de Referência e Treinamento; HSP, Hospital São Paulo; HUPES, Hospital Universitário Professor Edgard Santos; IVDU, intravenous drug users; MSM, men who have sex with men; SD, standard deviation.
The proportion of blacks was higher in Salvador than in São Paulo. In contrast, current smoking was less frequent among patients in Salvador, although past smoking frequency was similar for the three sites. The prevalence of smoking patients increased over time among patients in São Paulo's sites, whereas in Salvador smoking prevalence dropped from 29% at first visit to 13% in the last one. In addition, there was a higher proportion of men who have sex with men in CRT than in HUPES [prevalence ratio (PR): 1.4, 95% CI: 1.2–1.7, p < .001]. The mean CD4 count increased from 199 ± 169 cells/mL from baseline to 691 ± 345 cells/mL in the last visit (p < .01).
The most frequent (4%) NCD detected at baseline was dyslipidemia. However, at last visit, 107 patients (26.7%) had lipids abnormalities. Diabetes increased from 3.3% to 14.9%, stroke from 0.7% to 4.4%, myocardial infarction from 0.2% to 3.0%, hypertension from 13.7% to 34.8%, and malignancies from 0.7% to 3.1% (p < .001 for all comparisons). There was a 10 times increase in the frequency of patients using lipid-lowering drugs or drugs for treating diabetes (p < .001 for all comparisons). Use of antihypertensive drugs also increased 2.5 times in the period.
Our results show a significant increase in all main NCD in HIV patients >50 years. We observed a 6- to 15-fold increase in NCD frequency from first to last medical visits. These findings also reflect differences in routine screening according to site. This can explain why there were no cases of osteoporosis in patients at HUPES, where DEXA scan is not available, and it indicates that the overall frequency of some of these problems are underestimated.
São Paulo and Salvador are the first and fourth largest cities in Brazil, respectively. However, lifestyle and socioeconomic levels clearly differ for São Paulo and Salvador: Salvador is a coastal city, with strong African heritage, whereas São Paulo is an inner city, with a population originated from European/Asian countries and from other Brazilian states. Salvador has one of the lowest Human Development Index in Brazil, whereas São Paulo is the most developed state in the country. 6 The main findings of our study are consistently detected in all three sites, but some differences are evident, as observed in the higher frequency of blacks in Salvador and higher prevalence of smoking in São Paulo's patients. Even in São Paulo we could detect some differences between sites, which demonstrate that changes in the aging pattern are also dependent on the characteristics of patients attended at each site.
The high proportion of patients with undetectable PVL indicates a high level of adherence to ART in older patients. In addition, although the mean baseline CD4 cells count was <200 cells/mL, the current mean CD4 count was >600 cells/mL for all sites. The CRT has a significantly lower mean CD4 cells count, than that observed for patients followed at HSP or HUPES. Again, it can be the result of characteristics of populations in each site.
The available evidences make clear that aging with HIV is associated with increased number of NCD and polypharmacy. These problems can affect the health-related quality of life of PLHIV, can increase the risk of drug–drug interactions, and treatment-related adverse events, and negatively impact adherence to ART. 7 In contrast, some published studies show that older patients are more likely to have undetectable HIV plasma viremia and a better adherence to therapy. 8
Accelerating aging is considered a consequence of HIV infection and chronic use of ART. However, the available evidences suggest an important role of lifestyle characteristics as a factor that influences the speed of aging in HIV-infected patients. In a recent article, Sabin and Reiss call the attention for other potential confounding factors associated with accelerated aging in HIV patients, and that minimizes the actual effect of HIV-related problems in such process. 9 In contrast, a recent study in Brazil demonstrated that comorbidities are more common and develop earlier in HIV-positive patients than in HIV-negative controls. Multimorbidity (two or more comorbidities) was also associated with PVL, CD4 count (nadir and current), and type of antiretroviral therapy used by patients. 10
Our study was based on medical charts review, which makes possible that relevant information can be missed, due to underreporting/recording. However, it was based in three large referral centers, and the sample size was robust enough to provide consistent information on the population study. The use of consecutive inclusion avoided selection bias, once it was based on the routine medical visits schedule.
Taken together, our results show that aging with HIV is associated with increasing frequency of NCD and of pill burden, due to concomitant treatment required by this population. This can negatively impact the health-related quality of life for this population.
Footnotes
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.