Determinants of late disease-stage presentation at diagnosis of HIV infection in Venezuela: A case-case comparison

1742-6405-5-6 1742-6405 Research Determinants of late disease-stage presentation at diagnosis of HIV infection in Venezuela: A case-case comparison Bonjour A Maeva maeva.bonjour@gmail.com Montagne Morelba morelba_m@yahoo.com Zambrano Martha marthabruzual@hotmail.com Molina Gloria glomola@yahoo.es Lippuner Catherine clippuner@gmail.com Wadskier G Francis magusa86@hotmail.com Castrillo Milvida milvida@cantv.net Incani N Renzo rincani@uc.edu.ve Tami Adriana adriana.tami2@gmail.com

Department of Biomedical Research, Royal Tropical Institute, Amsterdam, The Netherlands

Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Centre for Integral Attention for Sexually Transmitted Diseases and HIV/AIDS, National Program of HIV/AIDS, Ministry of Health and Social Development, Valencia, Venezuela

Department of Biology and Society, Faculty of Earth and Life Sciences, Free University of Amsterdam, Amsterdam, The Netherlands

Department of Parasitology, Faculty of Health Sciences, University of Carabobo, Valencia, Venezuela

Centre of Information Technology, Communication and Assisted Education, Faculty of Health Sciences, University of Carabobo, Valencia, Venezuela

AIDS Research and Therapy 1742-6405 2008 5 1 6 http://www.aidsrestherapy.com/content/5/1/6 18416849 10.1186/1742-6405-5-6 05 10 2007 16 4 2008 16 4 2008 2008 Bonjour et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Although Venezuela has a National Human Immunodeficiency Virus (HIV) Program offering free diagnosis and treatment, 41% of patients present for diagnosis at a later disease-stage, indicating that access to care may still be limited. Our study aimed to identify factors influencing delay in presenting for HIV-diagnosis using a case-case comparison. A cross-sectional survey was performed at the Regional HIV Reference Centre (CAI), Carabobo Region, Venezuela. Between May 2005 and October 2006 225 patients diagnosed with HIV at CAI were included and demographic, behavioural and medical characteristics collected from medical files. Socio-economic and behavioural factors were obtained from 129 eligible subjects through interviews. "Late presentation" at diagnosis was defined as patients classified with disease-stage B or C according to the 1993 Centers for Disease Control and Prevention (Atlanta, USA) classification, and "early presentation" defined as diagnosis in disease-stage A.

Results

Of 225 subjects, 91 (40%) were defined as late presenters. A similar proportion (51/129) was obtained in the interviewed sub-sample. Older age (>30 years), male heterosexuality, lower socio-economic status, perceiving ones partner to be faithful and living ≥ 25 km from the CAI were positively associated with late diagnosis in a multivariate model. Females were less likely to present late than heterosexual males (odds ratio = 0.23, P = 0.06). The main barriers to HIV testing were low knowledge of HIV/AIDS, lack of awareness of the free HIV program, lack of perceived risk of HIV-infection, fear for HIV-related stigma, fear for lack of confidentiality at testing site and logistic barriers.

Conclusion

Despite the free Venezuelan HIV Program, poverty and barriers related to lack of knowledge and awareness of both HIV and the Program itself were important determinants in late presentation at HIV diagnosis. This study also indicates that women; heterosexual, bisexual and homosexual men might have different pathways to testing and different factors related to late presentation in each subgroup. Efforts must be directed to i) increase awareness of HIV/AIDS and the Program and ii) the identification of specific factors associated with delay in HIV diagnosis per subgroup, to help develop targeted public health interventions improving early diagnosis and prognosis of people living with HIV/AIDS in Venezuela and elsewhere.

Background

With an estimated 110,000 people living with Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) (PLWHA) in 2005, Venezuela is among the countries with the highest HIV prevalence (0.7% in adults) in Latin America 1. The ratio men to women gradually changed from 19:1 in the eighties to 2:1 in 2004 2. As in the rest of Latin America, HIV is mostly spread through sexual transmission, accounting for 90% of all reported HIV-infections between 1982 and 1999 3. Of the reported sexual transmissions of HIV 65% in that period involved men who had sex with men 3. However, as the epidemic matures the proportion of infected heterosexual men and women is rising 2. Analyses of data collected from 1999 to 2004 in Carabobo State showed that heterosexual transmission occurred in 61% of the cases 4.

Since 1999, the Venezuelan National HIV/AIDS Program (PNSIDA in Spanish) provides free comprehensive care for PLWHA, including diagnosis and monitoring, antiretroviral therapy (ART), treatment of opportunistic infections and other sexually transmitted infections (STIs), and prevention of mother-to-child transmission 5. In 2005, almost 16,000 PLWHA received free ART 2. However, of those estimated to require treatment in Venezuela in 2005, 16% did not receive it 6. A recent study in Carabobo State found that 41% (196/491) of the HIV-infected patients attending the PNSIDA between 1999–2004 presented for diagnosis at a later disease stage 4. This indicates that there are other factors hindering access to HIV-care than cost of diagnosis and treatment.

Early diagnosis of HIV-infection has benefits for the patient, public health and the society as a whole. Patients diagnosed at a late stage have poorer prognosis 7, whereas when started early, ART is more effective 891011 and with early diagnosis psychosocial aspects can be better dealt with 12. Early diagnosis also reduces HIV-transmission through clinical and behavioural preventive measures 1314. Finally, the early detection of HIV-infection has proven to be economically beneficial 1516 and to improve healthcare system planning capabilities 17.

Few studies have focused on these issues in Latin America 1819. A high proportion of individuals in Venezuela discover they are HIV-infected too late to fully benefit from ART. However, little research has been performed on the impact of government HIV programmes and the knowledge and behaviour of the targeted populations 20. Here we report the identification of factors associated with late presentation at HIV-diagnosis concomitantly with perceived barriers to testing in Venezuela. We furthermore highlight the importance of understanding region-specific determinants in order to improve the impact of free HIV-programs.

Results

Between the 1st of May 2005 and the 31st of October 2006, 226 individuals were newly diagnosed with HIV at the Reference Centre for Sexually Transmitted Infections and HIV/AIDS (CAI, in Spanish) in Valencia, Carabobo region, Venezuela. One individual was excluded from the study as the patient's medical file could not be located. The outcome of interest, 'late presentation' (disease stage B or C at HIV-diagnosis 21), occurred in 40% (91/225) of the individuals in agreement with a previous study 4.

Of the 225 included individuals, 129 (57%) were interviewed between the 25^thof April and the 25^thof October 2006. Of the 96 remaining eligible subjects one died, a second moved away, a third could not answer the questionnaire and three refused to participate; a further 90 were not interviewed either because they never attended the clinic during the study period, or because the interviewers were not available when they did. The average time between HIV diagnosis and interview was 4 months. Data collected from the patients' medical files was used to describe the total study population (n = 225). To test how representative the interviewed sample was, possible differences between the interviewed (n = 129) and non-interviewed individuals (n = 96) were examined by comparing the distribution of age, sex, marital status, education level, occupation, sexual orientation, HIV disease-stage classification 21, CD4⁺count, number of casual partners, condom and alcohol use and drug abuse between the two groups at the moment of HIV diagnosis (data not shown). There were no statistically significant differences except for sexual orientation, where a lower proportion of male heterosexuals was interviewed (26% vs. 47%; P = 0.001).

Demographic, socio-economic and behavioural factors

The mean age was 33 years (range 15–79 years) with the majority (67%) of individuals between 20 and 40 years old and a male/female ratio of nearly 4:1 (Table 1). Most of the single (111/132) and married persons (11/15) were men, while half (32/60) of the unmarried people living with a partner were women. Only 3 females self-identified as homo- or bisexual. Bi- and homosexuals were more likely to have finished secondary school than heterosexuals (70% vs. 33%; P < 0.001).

Table 1

Demographic and socio-economic factors associated with late presentation at HIV diagnosis in Venezuela, Carabobo State.

Late presenters

Total

OR*(95%CI)

P -value ( P^T)

SOCIO-DEMOGRAPHIC

Sex^{a, †}

Male

44.2

163

Female

30.6

0.57 (0.30–1.10)

0.094

Age (years)^a,‡

< 20

17.6

- (0.003)

20–29

27.0

1.74 (0.46–6.64)

0.417

30–39

55.7

6.02 (1.56–23.30)

0.009

>40

51.7

4.86 (1.25–18.84)

0.022

Marital Status^a(n = 224)

Single

40.9

132

Married

47.4

1.06 (0.38–2.95)

0.912

Divorced

75.0

3.06 (0.56–16.77)

0.198

Widowed

40.0

0.69 (0.11–4.48)

0.693

Living together

33.3

0.86 (0.42–1.74)

0.670

Children^a(n = 219)

32.1

109

≥ 1

47.3

110

2.06 (1.11–3.83)

0.022

Sexual orientation^a

Heterosexual

43.5

138

Bisexual

47.2

0.76 (0.33–1.71)

0.503

Homosexual

27.5

0.40 (0.18–0.87)

0.020

Education level^a

Not finished secondary school

46.6

118

Secondary school and higher

33.6

107

0.57 (0.32–1.01)

0.053

SOCIO-ECONOMIC

Type of occupation^a(n = 223)

Unemployed

42.1

Domestic worker

35.5

2.35 (0.54–10.28)

0.258

Manual worker

56.8

1.73 (0.55–5.46)

0.347

Self-employed/Commerce

50.0

1.41 (0.45–4.44)

0.555

Paid employee/Office worker

27.5

0.57 (0.18–1.79)

0.334

Professional/University staff

33.3

0.53 (0.11–2.55)

0.426

Student

31.8

1.38 (0.35–5.52)

0.646

Area of residence^b

Rural

57.1

Urban

37.4

115

0.34 (0.10–1.15)

0.082

Ownership residence^b

Owning

50.0

- (0.008)

Renting

26.7

0.30 (0.11–0.81)

0.017

Borrow/lodged

24.0

0.38 (0.13–1.10)

0.074

Socio-economic status^b,§

Low

50.0

High

29.2

0.24 (0.10–0.57)

0.001

Older age (≥ 30 years), having children and lower education level showed a significant positive association with late presentation for HIV-testing (Table 1). Women were almost half as likely to present late as men, while homosexuals were less likely to present late than heterosexuals. Although socio-economic factors did not show a clear association except for ownership of residence, the compound variable "Socio-economic status" (SES, see Methods) indicated that individuals with lower SES were more likely to be late presenters at HIV-diagnosis (Table 1).

Late presentation was not associated with alcohol consumption, drug abuse or condom use. The proportion of late presenters was lower among those having a steady partner, however this effect was mostly found for those who knew their steady partner was HIV-infected (Table 2). Moreover, perceiving their steady partner to be unfaithful, which could be a proxy for risk perception, showed a negative association with late presentation. There was an increased trend to present late the longer a person had a steady partner (Table 2).

Table 2

Behavioural characteristics and knowledge attributes associated with late presentation at HIV diagnosis in Venezuela, Carabobo State.

Late presenters

Total

OR*(95%CI)

P -value ( P^T)

BEHAVIOURAL CHARACTERISTICS

Alcohol use^a(n = 221)

No alcohol

47.1

Social drinker

34.0

0.49 (0.25–0.97)

0.041

Moderate drinker

39.1

0.55 (0.24–1.25)

0.155

Alcoholic

70.0

1.61 (0.35–7.44)

0.541

Drug abuse^a(n = 215)

42.1

195

Yes

40.0

0.91 (0.34–2.44)

0.855

Lifetime casual partners^b(n = 114)

28.6

- (0.286)

1–10

34.8

1.66 (0.40–6.97)

0.489

>10

47.5

2.72 (0.60–12.48)

0.197

Steady partner^a(n = 219)

48.6

107

- (0.021)

Yes, partner HIV^-or unknown HIV status

40.3

0.66 (0.16–2.65)

0.558

Yes, partner HIV⁺

24.0

0.42 (0.19–0.92)

0.030

Perception faithfulness steady partner^b

Faithful

56.1

Unfaithful/Doubting faithfulness

16.0

0.18 (0.05–0.66)

0.010

No steady partner

38.1

0.49 (0.21–1.12)

0.094

Time with steady partner (months)^{a, †}(n = 106)

<24

20.8

- (0.010)

25–120

40.0

2.49 (0.95–6.52)

0.063

>120

53.8

3.01(0.75–12.15)

0.121

Condom use^a(n = 169)

Never

38.2

102

Sometimes

36.1

0.95 (0.40–2.26)

0.911

Often

38.9

0.96 (0.32–2.94)

0.946

Always

46.2

0.71 (0.21–2.41)

0.583

Contact with commercial sex workers^b,‡(n = 93)

34.4

Yes

62.1

2.54 (0.99–6.54)

0.054

KNOWLEDGE ATTRIBUTES

Knowledge-HIV-transmission score^b,§

0 = no knowledge

63.6

- (0.033)

1–8 = poor knowledge

56.3

0.94 (0.18–5.03)

0.944

9–15 = good knowledge

34.3

102

0.32 (0.08–1.26)

0.103

Awareness HIV test^b

Not aware of existence

64.3

- (0.089)

Aware of existence, but not aware it was for free

38.2

0.39 (0.11–1.38)

0.143

Aware of existence and that it was for free

34.0

0.31 (0.08–1.14)

0.078

Awareness treatment^b

Not aware of existence

40.0

Aware of existence, but not aware it was for free

34.1

0.79 (0.34–1.84)

0.580

Aware of existence and that it was for free

48.0

1.03 (0.37–2.86)

0.951

Awareness PNSIDA score^b,** (n = 128)

0 = no awareness

63.6

- (0.055)

1–4 = some awareness

38.5

0.32 (0.08–1.29)

0.109

5–7 = good awareness

33.3

0.20 (0.04–1.05)

0.057

Total-HIV-knowledge score^b,††(n = 128)

0–14 = low overall knowledge

51.3

15–28 = high overall knowledge

34.8

0.51 (0.23–1.13)

0.096

^aData source: patient files (n = 225). ^bData source: questionnaires (n = 129). Missing values are deducted by subtracting the total of individuals for each variable to the corresponding 225 (a) or 129 (b) patients. If totals are not indicated for a variable, it has no missing values. *Adjusted for age group and sex. ^†Only those with steady partner were included (n = 112). ^‡Only men were included (n = 94). ^§Calculated from a 15-item HIV transmission question. **Calculated by adding all awareness variables. ^††Calculated by adding knowledge HIV transmission score, awareness PNSIDA score and one point for each correct answer to 6 true-or-false statements about HIV/AIDS. OR, odds ratio; CI, confidence interval; P^T, Mantel-Haenszel Score test for trend P-value.

Knowledge of HIV/AIDS

The majority of interviewed people (125/129) indicated they had heard about HIV. The main sources of information were the media, family/friends and school. Most people (118/129) said they knew how HIV was transmitted. Awareness of the existence of an HIV control program was low. Most people knew that an HIV-test existed but 59% (68/115) of these were not aware that the test was freely available (Table 2). Among the latter, 53% did not know how much a test would cost. Fewer people knew that treatment existed and only 25 knew it was available for free (Table 2).

Individuals who had never heard of HIV were more likely to be late at diagnosis than those who had (50% vs. 39%), but this effect was not significant (P = 0.662), possibly due to small sample size in the first group (n = 4, data not shown). Having heard about HIV at school decreased the likelihood of late presentation (OR, 0.39; 95% confidence interval (CI), 0.15–1.01), while none of the other sources of information showed any effect (data not shown). There was a decreasing trend for late presentation with increasing knowledge of HIV-transmission and awareness of the PNSIDA (Table 2). Awareness of existence and free availability of HIV testing was negatively associated with late presentation while no association was found for awareness of treatment availability. Persons with a low total-HIV-knowledge score were twice as likely to present late (P = 0.096, Table 2).

Risk perception and barriers and facilitators for testing

More than half of the interviewees had felt at risk of HIV-infection before diagnosis (Table 3). The main reasons mentioned for this risk perception were having unprotected sex (n = 21), having many sexual partners (n = 21), having homosexual partners (n = 10), having an unfaithful partner (n = 7), and having an HIV-positive partner (n = 7). The main reasons mentioned for not feeling at risk were having a steady partner (n = 25), not being aware of their own risk behaviour (n = 18), not knowing about HIV (n = 10), having protected sexual intercourse (n = 8), and not having any symptoms (n = 7). The time span people felt at risk before HIV-diagnosis ranged from 1 month to 12 years, with a geometric mean of 10 months. Of those who felt at risk, almost half (31/67) indicated no health-seeking behaviour, 16 (24%) started protecting themselves or turned to family, friends or their partner for advice, and 18 (27%) went to a health centre or the CAI. The majority of the interviewed persons (71/129) indicated to have perceived no barriers to HIV-testing. This may in part be explained by lack of perception of risk for HIV-infection, since those who had felt at risk were 7 times more likely to have mentioned any barriers (P < 0.001). Fourteen individuals (11%) mentioned at least one of the barriers categorized under 'confidentiality testing site,' while 32 individuals (25%) mentioned barriers from the category 'fear for stigma' and 12 (9%) mentioned items indicating logistical barriers (see Methods for definitions of categories).

Table 3

Risk perception, barriers to testing and final model of factors independently associated with late presentation at HIV diagnosis in Venezuela, Carabobo State.

Late presenters

Total

OR* (95%CI)

P -value

PERCEPTION OF RISK

Felt at risk of HIV infection (asked directly)^b

41.9

Yes

37.3

0.83 (0.39–1.79)

0.638

No perception of risk (mentioned as barrier)^b(n = 122)

Not mentioned

35.0

103

Mentioned

63.2

4.33 (1.40–13.33)

0.011

Health-seeking behaviour when felt at risk^b,†(n = 65)

No health-seeking behaviour

45.2

Protect oneself or seek advice family/friends/partner

37.5

0.52 (0.13–2.05)

0.347

Seek advice health centre/CAI

16.7

0.19 (0.04–0.88)

0.034

BARRIERS TO TESTING

Confidentiality testing site^b,‡(n = 117)

Not mentioned

37.9

103

Mentioned

57.1

2.30 (0.71–7.50)

0.167

Fear for stigma^b,§(n = 125)

Not mentioned

37.6

Mentioned

43.8

1.41 (0.60–3.33)

0.434

Logistic constraints^b,** (n = 119)

Not mentioned

36.4

107

Mentioned

66.7

3.95 (1.05–14.81)

0.042

Having no signs or symptoms^b

Not mentioned

33.6

113

Mentioned

81.3

4.33 (1.40–13.33)

0.011

Not-wanting-to-know HIV-status^b(n = 127)

Not mentioned

35.0

103

Mentioned

58.3

2.53 (0.93–6.86)

0.069

Distance to CAI^a

≤ 25 km

37.0

192

> 25 km

60.6

3.15 (1.39–7.14)

0.006

Final model of factors independently associated with late presentation at HIV diagnosis (n = 123/129)

Factors

OR^††(95% CI)

P -value

Age

<30 years

≥ 30 years

5.34 (1.70–16.76)

0.004

Sexuality

Male heterosexual

Male homosexual

0.22 (0.05–0.92)

0.039

Male bisexual

2.38 (0.46–12.41)

0.302

Female

0.23 (0.05–1.06)

0.059

Perception faithfulness partner

Faithful

Unfaithful/Doubting faithfulness

0.078 (0.01–0.56)

0.011

Distance to CAI

<25 km

≥ 25 km

16.69 (3.02–92.11)

0.001

^aData source: patient files (n = 225). ^bData source: questionnaires (n = 129). Missing values are deducted by subtracting the total of individuals for each variable to the corresponding 225 (a) or 129 (b) patients. If totals are not indicated for a variable, it has no missing values. *Adjusted for age group and sex. ^†Only those who indicated to feel at risk of HIV infection were included (n = 67). ^‡Set as 'mentioned' if: confidentiality test, doubt correctness result, attitude personnel or being seen at site was mentioned or agreed. ^§Set as 'mentioned' if: fear of loosing partner/family/job/children or fear for rejection was mentioned or agreed. **Set as 'mentioned' if: no time, inconvenient location, no transport money, costs treatment or costs test was mentioned or agreed. ^††Adjusted for SES, having an HIV⁺partner, total-HIV-knowledge score, testing as part of screening and the other variables in this model. OR, odds ratio; CI, confidence interval.

Although not significant, late presentation was slightly higher among those that had not felt at risk of HIV-infection than those who did when the question "did you feel at risk" was asked directly. However, mentioning not to have perceived themselves to be at risk as a barrier to HIV-testing showed a strong association with late presentation, even after adjusting for age group and sex (Table 3). People who had perceived barriers to HIV-testing were more likely to present late but this effect was not significant (P = 0.344). For the categories of barriers 'fear for stigma' and 'confidentiality testing site' a similar non significant association was found. Persons indicating logistical constrains were almost 4 times more likely to present late (P = 0.042; Table 3). Mentioning not-wanting-to-know their HIV status was associated with late presentation (Table 3), while mentioning fear to be diagnosed positive was not (OR, 1.00; 95%CI 0.39–2.59), indicating that this might have a bi-directional effect on testing behaviour. Of the 13 persons that presented late and mentioned not-having-symptoms-yet as a barrier, 9 (69%) had felt at risk, indicating that feeling healthy might prevent people from converting their perception of risk into the act of HIV-testing. Persons living ≥ 25 km away from the CAI were 3 times more likely to present late than those who did not(Table 3). However, reported time and transport costs to CAI were not associated with late presentation.

Taking the HIV-test on their own initiative (50/129) or for health-related reasons (47/129) were mentioned by most individuals, while the remaining 32 individuals mentioned screening as the reason for testing. Testing on own initiative was negatively associated with late presentation (OR, 0.44; CI, 0.21–0.94), while testing for health-related reasons increased the likelihood of being late 8 times (P < 0.001, Figure 1). Of those tested as part of screening, 13% was still diagnosed in a late stage of HIV-infection.

Figure 1

Proportion of early and late presenters, by reason for testing

Proportion of early and late presenters, by reason for testing. Screening consisted of screening at blood bank, antenatal and pre-surgery screening and screening as part of health certification; Own initiative consisted of testing because of curiosity, feeling at risk of HIV-infection, having had STIs, many sexual partners, unprotected sex, an unfaithful partner, or testing on advice of partner, family or friends; Health-related consisted of referral by a health centre, the respondent or partner showing HIV-related symptoms and having HIV-infected partners or children. *P <0.05. ^†Number of individuals is noted within each bar.

Multivariate analysis

For a final model, sexual orientation and sex were combined into one variable ('sexuality') with women, heterosexual men, homosexual men and bisexual men as the four categories. Persons living <25 km away from the CAI, of younger age, that did not perceive their partner to be faithful and women and homosexual men remained less likely to present late after adjusting for SES, having an HIV⁺partner, overall HIV knowledge, and screening as reason for testing (Table 3).

Discussion

This study is, to our knowledge, the first in Latin America to have explored factors associated with late presentation at HIV-diagnosis concomitantly with perceived barriers to testing. Only two other studies have been performed in Latin America; a study in French Guiana examined determinants of late HIV-diagnosis 19 and another in Brazil looked at barriers to testing during antenatal care 18. In developed and Sub-Saharan African countries, most studies either focus on perceived barriers and attitudes to voluntary testing 22232425 or on determinants of late presentation for HIV-testing 1026272829. Few studies have actually examined the pathway – and hurdles – of those who present late for HIV-diagnosis, and most of them were carried out in developed countries 303132. Using a case-case comparison this study has identified factors involved with late presentation for HIV-diagnosis within a free HIV-program in Latin America. In line with other studies examining HIV-testing behaviour and late presentation, we have found that older age 710192633, lower educational level 1827, lower SES 28 and heterosexual orientation in men 101228 increase the likelihood of late presentation. Moreover, lack of knowledge about HIV/AIDS 34, lack of awareness about the free services provided by the PNSIDA, lack of perceived risk of infection 23242835, psychological barriers 232528343536 and logistical constraints 232436 are associated with this delay in HIV-testing.

Since it is difficult to determine the moment of infection, low CD4⁺-cell count at diagnosis 19262930 or rapid progression to AIDS 1027283137 have been used to define late presentation. In contrast, we used the CDC classification system for HIV-infection 21 encompassing the whole clinical picture at the moment of diagnosis which allowed the inclusion of all individuals newly diagnosed within the period of study. Our case definition was deliberately chosen to avoid ascertainment bias in our study population since around 60% of individuals do not have a CD4 count up to at least three months after HIV diagnosis 4