Open Access

Changes in blood pressure, glucose levels, insulin secretion and anthropometry after long term exposure to antiretroviral therapy in South African women

  • Zulfa Abrahams1,
  • Joel A Dave1,
  • Gary Maartens2 and
  • Naomi S Levitt1Email author
AIDS Research and Therapy201512:24

https://doi.org/10.1186/s12981-015-0065-8

Received: 1 May 2015

Accepted: 28 July 2015

Published: 5 August 2015

Abstract

Background

A number of metabolic abnormalities, such as dysglycaemia, insulin resistance, lipodystrophy and dyslipidaemia, are associated with the use of antiretroviral drugs. We aimed to assess the effects of long-term antiretroviral exposure on blood pressure, glycaemia, insulin secretion and anthropometric measures in black South African women.

Methods

A convenience sample of HIV-infected women on first-line ART for a median of 16 months at baseline, had the following evaluations twice, at baseline and after approximately 5 years: anthropometry, including skin fold thicknesses, blood pressure, oral glucose test, and insulin. Insulin sensitivity and secretion (HOMA-IR, IGI and DIo) were estimated.

Results

At baseline more than half the 103 women were using stavudine and efavirenz. The median interval between baseline and follow-up evaluation was 66 months. Weight, waist circumference, and waist-hip ratio increased over time, while limb skinfold thickness decreased over time. Systolic and diastolic blood pressure increased significantly and the proportion of participants with hypertension increased from 3.9 to 15.5% (p < 0.001). There were increases from baseline in plasma glucose concentrations at 30 and 120 min; insulin concentrations at 0 and 30 min; and IGI and DIo. The proportion of participants with diabetes increased from 1 to 7.5% (p = 0.070).

Conclusion

In black South African women with long-term exposure to ART, increases in hypertension and possibly diabetes were observed. Participants experienced an increase in central fat and a decrease in peripheral fat distribution. Early identification and management of these metabolic changes are important, especially in a region with the highest HIV-infected population in the world.

Keywords

HIV Dysglycaemia Hypertension Antiretroviral therapy Body composition Lipoatrophy Blood pressure

Background

Africa has made great strides in expanding access to antiretroviral therapy (ART), with an estimated 7.6 million people in sub-Saharan Africa receiving treatment by December 2012 [1]. The increase in access to ART has resulted in a dramatic decline in HIV-related deaths. However, several antiretroviral drugs are associated with a number of metabolic abnormalities [2] including dyslipidaemia, lipodystrophy, insulin resistance and dysglycemia [3].

Several studies from Africa have shown an increased prevalence of dysglycaemia in HIV-infected patients, especially in patients on ART, but the duration of ART exposure was generally under 3 years [46]. There are conflicting data with regard to the impact of HIV and ART on hypertension, with some studies showing an increased risk of hypertension [7, 8] and others showing no association [911]. A recent systematic review [12] found that HIV-infected patients in sub-Saharan Africa, irrespective of ART status, had lower systolic and diastolic blood pressure (BP) than HIV-uninfected controls.

ART-related lipoatrophy is common in low-and-middle income countries (LMICs) [1315], where stavudine has only recently been phased out and zidovudine is still widely being used. Anthropometric studies show that fat loss is best detected by triceps skinfold and hip circumference measurements [13, 16]. Central fat accumulation on ART is thought to be a consequence of treating the HIV infection, as the gain in trunk and visceral fat is no different between HIV-infected participants on ART and HIV-uninfected controls, and does not differ by antiretroviral class [17].

Little is known about the long-term metabolic effects of ART in LMICs. We aimed to assess the effects of long-term ART exposure on blood pressure, glycaemia, insulin secretion and anthropometric measures in black South African women.

Results

Participant characteristics are presented in Table 1. We enrolled 103 of the 345 women assessed at baseline for follow-up assessment. At baseline the participants had spent a median of 16 months on first-line ART and almost all were using stavudine (91%) and lamivudine (100%). At follow-up 84% were still on first-line ART but the percentage of those using stavudine had decreased to 39%, and those using zidovudine had increased from 10 to 38%. The median time on ART at follow-up was 82 months (6.8 years).
Table 1

Comparison of baseline and follow-up characteristics of female participants

 

Baseline median (IQR), n = 84

Follow-up median (IQR), n = 77

Age

33.5 (30.0–40.0)

40.1 (35.7–45.4)

Current CD4 count

372 (261–471)

564 (427–774)

Time on ART (months)

16.0 (10.0–26.0)

82.4 (73.8–94.1)

 

n (%)

n (%)

No schooling

5 (4.8)

 

Primary School

14 (13.6)

 

Secondary School

83 (80.6)

 

Tertiary

1 (1.0)

 

1st line ART

84 (100)

65 (84.4)

2nd line ART

0 (0)

12 (15.6)

Stavudine

76 (90.5)

30 (39.0)

Lamivudine

84 (100)

77 (100)

Zidovudine

8 (9.5)

29 (37.7)

Tenofovir

0 (0.0)

18 (23.4)

Lopinavir

0 (0.0)

12 (15.6)

Efavirenz

41 (48.8)

36 (46.8)

Nevirapine

43 (51.2)

29 (37.7)

As shown in Table 2, waist circumferences increased significantly (p = 0.038), while hip and mid-thigh circumferences decreased (p < 0.001). All skinfold thicknesses changed significantly from baseline to follow-up. All 25% of the participants who reported having lipoatrophy at baseline, reported none at follow-up. However, when using objective measures [13] based on thigh and triceps cut points, the percentage of participants with lipoatrophy increased from 44 to 64%; p = 0.010. At baseline, 60% of those who self-reported moderate or severe fat loss in 2 or more regions, were correctly classified using thigh and tricep skinfold cut points, while 61.5% of those who reported having lost none, or minimal amounts of fat were correctly classified (p = 0.002).
Table 2

Comparison of anthropometric measures in females at baseline and follow-up (n = 103)

 

Baseline median (IQR), n = 103

Follow-up median (IQR) n = 94

P-value*

Height (m)

1.6 (1.5–1.6)

1.6 (1.5–1.6)

0.401

Weight (kg)

69.2 (61.4–81.1)

70.1 (59.7–78.8)

0.402

BMI

27.9 (24.8–31.8)

27.8 (23.9–31.6)

0.443

Sagittal height (cm)

21 (19–24)

20.6 (18.5–23.5)

0.640

Circumferences

 Waist (cm)

89.8 (81.3–96.8)

90.8 (82.5–100.0)

0.038

 Hip (cm)

103.0 (96.0–114.0)

100.0 (91.8–106.5)

<0.001

 Waist-hip ratio

0.86 (0.81–0.92)

0.92 (0.85–0.98)

<0.001

 Mid-upper arm (cm)

29.0 (27.0–32.0)

29.5 (26.8–32.5)

0.292

 Mid-thigh (cm)

58.0 (53.0–63.0)

55.0 (49.5–59.5)

<0.001

Skinfold thickness

 Biceps (mm)

8.1 (5.8–10.5)

9.0 (6.4–12.6)

0.011

 Triceps (mm)

19.0 (12.6–25.2)

16.3 (11.3–22.5)

0.007

 Abdomen (mm)

25.1 (16.9–34.2)

32.2 (21.7–37.8]

<0.001

 Thigh (mm)

32.8 (24.1–43.3)

24.3 (17.3–34.0)

<0.001

 Sub-scapular (mm)

21.5 (13.4–28.8)

29.0 (18.8–34.2)

<0.001

 Supra-iliac (mm)

16.1 (9.9–22.4)

20.5 (13.3–28.9]

<0.001

 Calf (mm)

17.8 (12.3–24.4)

13.1 (7.0–19.2)

<0.001

 

n (%)

n (%)

P-value**

Lipoatrophy

 Based on patient report

25 (24.5)

0

<0.001

 Based on thigh (≤28 mm) and triceps (≤14.5 mm) skinfold cut points

45 (43.7)

59 (64.1)

0.010

* Non-parametric paired t-test.

** McNemar Chi square test for paired data.

Both systolic and diastolic blood pressures increased (p < 0.001) from baseline to follow-up (Table 3). Plasma glucose concentrations at 30 and 120 min, and insulin concentrations at 0 and 30 min also increased significantly from baseline to follow-up (p < 0.050). Although the homeostatic assessment model (HOMA-IR) tended to increase (p = 0.089) from baseline to follow-up, both the insulinogenic index (IGI) and the oral disposition index (DIo) increased significantly (p < 0.001).
Table 3

Comparison of blood pressure, plasma glucose and insulin concentrations and markers of insulin sensitivity and beta cell function at baseline and follow-up (n = 103)

 

Baseline median (IQR)

Follow-up median (IQR)

P-value*

Blood Pressure

 Systolic

111 (101–121)

121 (112–133)

<0.001

 Diastolic

72 (64–80)

80 (73–89)

<0.001

Glucose

 Fasting

5.1 (4.7–5.4)

4.9 (4.7–5.3)

0.365

 30 min

6.6 (5.8–7.4)

6.8 (5.9–8.0)

0.040

 120 min

5.4 (4.9–6.3)

5.6 (4.7–6.8)

0.028

Insulin

 Fasting

5.6 (3.3–9.5)

7.9 (4.1–12.9)

0.009

 30 min

35.1 (19.2–66.7)

177.7 (163.4–192.5)

<0.001

 120 min

24.0 (13.5–40.2)

23.7 (10.4–54.9)

0.993

Glycaemic parameters (without diabetics and outliers)

 HOMA-IRa

1.2 (0.7–2.2)

1.6 (0.9–2.7)

0.089

 IGIb

23.7 (11.9–33.1)

80.0 (54.0–137.4)

<0.001

 DI o c

3.5 (2.3–7.9)

11.9 (4.9–23.3)

<0.001

* Non-parametric paired t-test.

aHOMA-IR = (fasting glucose × fasting insulin)/22.5.

bIGI = ΔInsulin0-30/ΔGlucose0-30.

cDIo [Oral disposition index] = (ΔInsulin0-30/ΔGlucose0-30) × (1/fasting insulin).

The proportion of participants with hypertension increased from baseline to follow-up, from 3.9 to 15.5%; p < 0.001 (Table 4). While the proportion of participants with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and dysglycemia did not change significantly from baseline to follow-up, there was a trend to an increase in the proportion of participants with diabetes (1% to 7.5%; p = 0.070). At baseline and follow-up, diabetes, hypertension and dysglycaemia were significantly associated with lipoatrophy (p < 0.001) based on thigh and tricep skinfold cut points.
Table 4

Comparison of blood pressure and glucose abnormalities in females at baseline and follow-up (n = 103)

 

Baseline n (%)

Follow-up n (%)

P-value*

Hypertension

3 (3.9)

16 (15.5)

<0.001

Glucose abnormalitiesa

 Diabetes

1 (1.0)

7 (7.5)

0.070

 Impaired glucose tolerance

6 (5.8)

9 (9.6)

0.344

 Impaired fasting Glucose

17 (16.5)

10 (10.5)

0.308

 Dysglycemia

22 (21.4)

19 (20)

1.00

* McNemar Chi square test for paired data.

an = 94 at follow-up.

Stavudine, efavirenz and nevirapine were significantly associated with diabetes, hypertension and dysglycaemia at follow-up (Table 5). Lipoatrophy was significantly associated (p < 0.001) with zidovudine, tenofovir, lopinavir in addition to stavudine, efavirenz and nevirapine.
Table 5

P-values* representing associations between diabetes, hypertension, dysglycaemia and lipoatrophy, and different antiretroviral drugs at follow-up

 

Diabetes

Hypertension

Dysglycaemia

Lipoatrophya

Stavudine

0.001

0.017

0.029

<0.001

Zidovudine

0.031

1

0.845

<0.001

Tenofovir

0.004

0.690

0.856

<0.001

Lopinavir

0.077

0.664

0.690

<0.001

Efavirenz

0.001

<0.001

<0.001

<0.001

Nevirapine

<0.001

0.029

0.029

<0.001

* McNemar Chi square test for paired data.

aDefined by thigh and tricep skinfold cut points.

Discussion

Our results show that long term exposure to ART in South African women is associated with increases in blood pressure, glucose and insulin levels. These women also experienced changes in body composition with a significant increase in the waist-hip ratio, and in the prevalence of lipoatrophy when objective anthropometric measures (thigh and triceps skinfold cut points [13]) were used instead of the subjective measure of patient report. These metabolic and body composition changes are all associated with an increased cardiovascular risk [18].

The prevalence of hypertension at baseline in our study was threefold lower than in women of a similar age-group from a similar area in Cape Town who participated in a community-based cardiovascular risk factor study (CRIBSA). At follow-up the prevalence of hypertension was lower when compared to similarly aged women from the CRIBSA Study. Although HIV testing was not performed in the CRIBSA Study, participants were not known to be on ART and based on local data, the HIV-infected proportion was estimated to be about 10% [19]. Another study from rural KwaZulu Natal, South Africa [20] reported a 20% prevalence of hypertension in HIV-infected women compared to 40% in HIV-uninfected women 15 years and older. The lower BMI in people on ART compared to the HIV negative participants may be an explanation for the lower prevalence of hypertension in both of these South African studies. In contrast, studies from Tanzania [7] and Uganda [7, 21] have reported a similar prevalence of hypertension in HIV-infected and HIV-uninfected participants, with those on ART in Tanzania having a higher BMI than those who were HIV-uninfected or HIV-infected and ART-naive.

Although the prevalence of new onset diabetes increased between baseline and follow-up in our study, this did not reach statistical significance, possibly due to the small sample size. Interestingly, the prevalence of new onset diabetes at follow-up, was twofold higher in our study than the prevalence of new onset diabetes in women of similar ages from the CRIBSA study [19]. The different methods used to assess dysglycaemia makes it difficult to compare studies from Africa. However, a study [22] that also used an OGTT to assess dysglycaemia found a similar prevalence of dysglycaemia, although the length of time on ART was longer in our study (81 months vs 48 weeks). The rise in insulin secretion in relation to insulin resistance, as expressed by the DIo, in the majority of the group at follow-up explains their lack of development of diabetes.

Although there was no increase in BMI at follow-up, the greater abdominal skinfold thickness and waist-hip ratio together with peripheral wasting suggests a marked difference in body composition with centralisation of body fat, in agreement with a number of other African studies [5, 13, 16, 23]. HIV-associated central fat accumulation likely reflects the consequence of treating the HIV infection rather than a specific antiretroviral adverse drug reaction [17]. We found an increase in the percentage of participants with lipoatrophy when defined by thigh and triceps skinfold cut points [13]. However, when using patient report to diagnose lipoatrophy, no women had lipoatrophy, including the 25% who reported lipoatrophy at baseline. The discrepancy we found in the proportion of women with lipoatrophy on anthropometry and patient report is likely due to the women having grown accustomed to their new body shape and illustrates the limitations of diagnosing lipodystrophy using a subjective measure. Lipoatrophy is an antiretroviral adverse drug reaction, strongly associated with the use of thymidine analogue nucleoside reverse transcriptase inhibitors (NRTI’s), stavudine and zidovudine [17]. In our study more than 30% of women were still on stavudine at follow-up and almost 20% were still taking zidovudine. The baseline prevalence of lipoatrophy we found is also similar to that of another South African study [16], which reported a 43% prevalence after 2 years of treatment, but they defined lipoatrophy only by subjective patient and healthcare worker reports.

Our study has some limitations. The lack of a HIV-uninfected and ART-naïve control groups limits our ability to attribute the changes observed to the use of ART. The sample size was also relatively small, which limited our ability to assess whether the increased prevalence of diabetes over time was significant. Despite these limitations, ours is one of very few studies in Africa to use an OGTT to define dysglycemia and to follow women on ART for over 5 years.

Conclusion

In this study from Africa we observed that women who had been on ART for more than 5 years, developed increased blood pressure (systolic and diastolic). The prevalence of hypertension and diabetes also increased. The greatest changes observed were in body composition, with an increase in central fat and a decrease in subcutaneous fat. The prevalence of lipoatrophy, when defined by skinfold cut points, increased substantially. These findings have important implications for the management of HIV in Africa. The early identification and management of these cardiometabolic risks are crucial in the region with the highest HIV-infected population in the world.

Methods

Participants

In our initial cross sectional study, undertaken in 2007–2008 to examine the metabolic consequences of ART, a convenience sample of 345 HIV-infected black African women on first-line ART who were being followed up at ART clinics in Cape Town were selected. The recruitment procedure is described elsewhere [5]. At that stage the first-line ART regimen consisted of stavudine, lamivudine or zidovudine and efavirenz or nevirapine, and the second-line regimen consisted of zidovudine with didanosine and lopinavir/ritonavir [24]. Subsequently, the first-line regimen was changed to tenofovir and efavirenz or nevirapine, and lamivudine replaced didanosine in the second-line regimen. NRTI drug substitutions for toxicity or the convenience of a fixed dose combination are not considered switches to 2nd line ART. 103 of the initial 345 participants could be traced approximately 5 years later and underwent repeated assessments. The remainder could not be traced using their home address or telephone number and were no longer attending the health facility from which they were recruited; defaulted, were pregnant or had died. The baseline characteristics did not differ between those we traced and those not traced.

Testing procedures

We used the same procedures to collect information from participants at baseline and follow-up. Socio-demographic information was collected using an interviewer administered questionnaire. Clinical records were obtained from health facilities and reviewed to obtain data on ART regimen, time on ART and, CD4 count. The Lipodystrophy Case Definition questionnaire [25] was used to collect self-reported information on fat gain or fat loss. Self-reported lipoatrophy was defined as in the HOPS study, as moderate or severe fat loss in 2 or more regions and self-reported lipohypertrophy defined as moderate or severe fat gain in two or more areas [26].

After an overnight fast, participants underwent a 75 g oral glucose tolerance test (OGTT). Venous blood samples were taken at 0, 30 and 120 min. The plasma was stored and analysed as previously described [5].

Anthropometric measurements: [weight, height, circumferences (waist, hip, mid-upper arm, and mid-thigh), skinfold thickness (biceps, triceps, subscapular, abdomen, suprailiac, thigh and calf) and sagittal abdominal diameter (SAD)] were also done. Cut point based lipoatrophy was defined as having a thigh skinfold thickness ≤28 mm or a triceps skinfold thickness of ≤14.5 mm [13]. Three BP measurements were taken at 2-min intervals using an Omron BP monitor with an appropriately sized cuff after the participant had been seated for 5 min. The average of the second and third BP measurements was used in the analyses. Hypertension was defined as BP ≥140/90 mmHg or using antihypertensive agents. Diabetes, IGT and IFG were defined using the American Diabetes Association criteria [27].

Ethical approval

The study proposal was submitted and approved by the Research Ethics Committee of the Faculty of Health Sciences at the University of Cape Town. Written informed consent was obtained from all participants prior to participation in the study, at baseline and again at follow-up.

Data analyses

Data analysis was carried out using the STATA/SE statistical software package version 12.0 (StataCorp., College Station, TX, USA). Baseline data were collected between February 2007 and June 2009 and follow-up data between July 2011 and July 2013. Because the data were not normally distributed, continuous variables were described as medians and inter-quartile ranges (IQR), and were compared using a non-parametric paired t test. Binary variables were described using numbers and percentages, and compared using the McNemar Chi square test for paired data.

Markers of beta cell function and insulin resistance were estimated in the participants who did not have diabetes at follow-up. Beta-cell function was estimated using (1) IGI, calculated as the ratio of the change in insulin to the change in glucose from 0 to 30 min (ΔInsulin0–30/ΔGlucose0–30), and (2) DIo, calculated as a (ΔInsulin0-30/ΔGlucose0–30) × (1/fasting insulin). Insulin resistance was estimated using HOMA-IR, calculated as (fasting glucose × fasting insulin)/22.5.

Declarations

Authors’ contributions

ZA conducted all statistical analyses, interpreted the findings and drafted the manuscript; JD, NL and GM designed and conducted the study; NL, GM, and JD edited the manuscript and drafted revisions. All authors read and approved the manuscript.

Acknowledgements

We thank Sasha West for anthropometric measurements and Carmen Delport for co-ordinating the study.

Compliance with ethical guidelines

Competing interests Supported by grants from the World Diabetes Foundation and the South African Department of Health. GM was supported in part by the National Research Foundation (NRF) of South Africa (grant specific unique reference number (UID) 85810). The Grant holder acknowledges that opinions, findings and conclusions or recommendations expressed in any publication generated by the NRF supported research are that of the authors, and that the NRF accepts no liability whatsoever in this regard.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Division of Diabetic Medicine and Endocrinology, Department of Medicine, University of Cape Town
(2)
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town

References

  1. UNAIDS: Access to antiretroviral therpy in Africa—status report on progress towards 2015 targets. 2013. http://www.unaids.org/sites/default/files/media_asset/20131219_AccessARTAfricaStatusReportProgresstowards2015Targets_en_0.pdf. Accessed 23 April 2015
  2. Schambelan M, Benson CA, Carr A, Currier JS, Dubé MP, Gerber JG et al (2002) Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA panel. J Acquir Immune Defic Syndr 31(3):257–275PubMedView ArticleGoogle Scholar
  3. Gutierrez AD, Balasubramanyam A (2012) Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms, and management. Endocrine 41(1):1–10PubMed CentralPubMedView ArticleGoogle Scholar
  4. Mutimura E, Stewart A, Rheeder P, Crowther NJ (2007) Metabolic function and the prevalence of lipodystrophy in a population of HIV-infected African subjects receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 46(4):451–455PubMed CentralPubMedView ArticleGoogle Scholar
  5. Dave JA, Lambert EV, Badri M, West S, Maartens G, Levitt NS (2011) Effect of nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy on dysglycemia and insulin sensitivity in South African HIV-infected patients. J Acquir Immune Defic Syndr 57(4):284–289PubMedView ArticleGoogle Scholar
  6. Omech B, Sempa J, Castelnuovo B, Opio K, Otim M, Mayanja-Kizza et al (2012) Prevalence of HIV-associated metabolic abnormalities among patients taking first-line antiretroviral therapy in Uganda. ISRN AIDS. doi:https://doi.org/10.5402/2012/960178
  7. Peck RN, Shedafa R, Kalluvya S, Downs JA, Todd J, Suthanthiran M et al (2014) Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study. BMC Med 12(1):125PubMed CentralPubMedView ArticleGoogle Scholar
  8. Gazzaruso C, Bruno R, Garzaniti A, Giordanetti S, Fratino P, Sacchi P et al (2003) Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome. J Hypertens 21(7):1377–1382PubMedView ArticleGoogle Scholar
  9. Ogunmola OJ, Oladosu OY, Olamoyegun AM (2014) Association of hypertension and obesity with HIV and antiretroviral therapy in a rural tertiary health center in Nigeria: a cross-sectional cohort study. Vasc Health Risk Manag 10:129PubMed CentralPubMedView ArticleGoogle Scholar
  10. Bergersen B, Sandvik L, Dunlop O, Birkeland K, Bruun J (2003) Prevalence of hypertension in HIV-positive patients on highly active retroviral therapy (HAART) compared with HAART-naive and HIV-negative controls: results from a Norwegian study of 721 patients. Eur J Clin Microbiol Infect Dis 22(12):731–736PubMedView ArticleGoogle Scholar
  11. Jerico C, Knobel H, Montero M, Sorli ML, Guelar A, Gimeno JL et al (2005) Hypertension in HIV-infected patients: prevalence and related factors. Am J Hypertens 18(11):1396–1401PubMedView ArticleGoogle Scholar
  12. Dillon DG, Gurdasani D, Riha J, Ekoru K, Asiki G, Mayanja BN, Levitt NS et al (2013) Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis. Int J Epidemiol 42(6):1754–1771PubMed CentralPubMedView ArticleGoogle Scholar
  13. Abrahams Z, Dave JA, Maartens G, Lesosky M, Levitt NS (2014) The development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings. AIDS Res Ther 66(6):839–844Google Scholar
  14. Menezes C, Maskew M, Sanne I, Crowther N, Raal F (2011) A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects. BMC Infect Dis 11(1):244PubMed CentralPubMedView ArticleGoogle Scholar
  15. van Griensven J, De Naeyer L, Mushi T, Ubarijoro S, Gashumba D, Gazille C et al (2007) High prevalence of lipoatrophy among patients on stavudine-containing first-line antiretroviral therapy regimens in Rwanda. Trans R Soc Trop Med Hyg 101(8):793–798PubMedView ArticleGoogle Scholar
  16. George JA, Venter WD, Van Deventer HE, Crowther NJ (2009) A longitudinal study of the changes in body fat and metabolic parameters in a South African population of HIV-positive patients receiving an antiretroviral therapeutic regimen containing stavudine. AIDS Res Hum Retroviruses 25(8):771–781PubMedView ArticleGoogle Scholar
  17. de Waal R, Cohen K, Maartens G (2013) Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction. PLoS One 8(5):e63623PubMed CentralPubMedView ArticleGoogle Scholar
  18. Stanley TL, Grinspoon SK (2012) Body composition and metabolic changes in HIV-infected patients. J Infect Dis 205(Suppl 3):S383–S390PubMed CentralPubMedView ArticleGoogle Scholar
  19. Peer N, Steyn K, Lombard C, Lambert EV, Vythilingum B, Levitt NS (2012) Rising diabetes prevalence among urban-dwelling black South Africans. PLoS One 7(9):e43336PubMed CentralPubMedView ArticleGoogle Scholar
  20. Malaza A, Mossong J, Bärnighausen T, Newell M (2012) Hypertension and obesity in adults living in a high HIV prevalence rural area in South Africa. PLoS One 7(10):e47761PubMed CentralPubMedView ArticleGoogle Scholar
  21. Semeere AS, Sempa J, Lwanga I, Parkes-Ratanshi R, Kambugu A (2014) Hypertension and associated risk factors in individuals infected with HIV on antiretroviral therapy at an urban HIV clinic in Uganda. The Lancet Global Health 2:S23View ArticleGoogle Scholar
  22. Manuthu EM, Joshi M, Lule G, Karari E (2008) Prevalence of dyslipidemia and dysglycaemia in HIV infected patients. East Afr Med J 85(1):10–17PubMedView ArticleGoogle Scholar
  23. Zinn RJ, Serrurier C, Takuva S, Sanne I, Menezes CN (2013) HIV-associated lipodystrophy in South Africa: the impact on the patient and the impact on the plastic surgeon. J Plast Reconstr Aesthet Surg 66(6):839–844PubMedView ArticleGoogle Scholar
  24. Department of Health (2013) The South African Antiretroviral Treatment GuidelinesGoogle Scholar
  25. Carr A (2003) An objective case definition of lipodystrophy in HIV-infected adults: a case-control study. Lancet 361(9359):726–735PubMedView ArticleGoogle Scholar
  26. Lichtenstein KA, Ward DJ, Moorman AC, Delaney KM, Young B, Palella FJ Jr et al (2001) Clinical assessment of HIV-associated lipodystrophy in an ambulatory population. AIDS 15(11):1389–1398PubMedView ArticleGoogle Scholar
  27. American Diabetes Association (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(Suppl 1):S62–S69PubMed CentralView ArticleGoogle Scholar

Copyright

© Abrahams et al. 2015

Advertisement