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JBI Database of Systematic Reviews & Implementation Reports 2014;12(4) 395 - 429

Feyissa & Demissie. Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in sub-Saharan African countries: © the authors 2014 doi:10.11124/jbisrir-2014-1383 Page 395

Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in sub-Saharan African countries: a systematic review

Garumma Tolu Feyissa, MPH1

Tariku Dejene Demissie, MSc2

1.Department of Health Education and Behavioral Sciences, Jimma University, Malaria Alert Center: a

Collaborating Center of the Joanna Briggs Institute, Ethiopia, Africa

2.Department of Epidemiology, Jimma University, Malaria Alert Center: a Collaborating Center of the

Joanna Briggs Institute, Ethiopia, Africa

Corresponding author:

Garumma Tolu Feyissa,

[email protected]

Executive summary

Background

A point of care (PoC) CD4 test is a CD4 test performed in the immediate vicinity of a patient to

provide a rapid same-day result outside the conventional laboratory environment, in order to

facilitate immediate clinical decision-making, including initiation and adjustment of anti-

retroviral therapy.

Objectives

The objective of this review was to determine the effect of point of care CD4 cell count tests

on retention of patients and rates of antiretroviral therapy initiation.

Inclusion Criteria

Types of participants

Adults living with HIV were included.

Types of intervention

Point of care CD4 testing

mailto:[email protected]



Types of studies

Both experimental and epidemiological study designs were included.

Types of outcomes

The primary outcomes were: attending a wellness program, initiation of antiretroviral treatment

of enrolled patients, loss to follow up before attending pre-ART care, loss to follow up before

ART initiation.

Search strategy

The search strategy aimed to find both published and unpublished studies reported from 2004

to July, 2013. After an initial search for articles in MEDLINE and CINAHL and after an analysis

of the text words contained in the title and abstract, and of the index terms used to describe

article, the references of the studies were also searched. The search for unpublished studies

included: Mednar, Google Scholar, and ProQuest Dissertations and Theses.

Methodological quality

Papers selected for retrieval were assessed by two independent reviewers for methodological

validity prior to inclusion in the review using standardized critical appraisal instruments from

the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument

(JBI-MAStARI).

Data collection

Data were extracted independently by the two reviewers using the standardized data

extraction tool from JBI-MAStARI.

Data synthesis

Data were pooled in statistical meta-analysis using JBI-MAStARI. All results were subjected to

double data entry. Before conducting meta-analyses, heterogeneity was assessed.

Results

The initial search identified 55 articles out which 11 articles were retrieved. After critical

appraisal, three articles were accepted to be included in data abstraction. Providing PoC CD4

tests had a significant effect on increasing treatment initiation. It did not decrease loss to

follow up before treatment initiation. Providing PoC CD4 tests did not have effect on

increasing the attendance of Pre-ART care and on decreasing follow up from Pre- ART care.

Conclusions

The review of primary studies conducted from 2004 to 2013 indicated that providing point of

care CD4 tests had significant effect on increasing ART initiation among adults living with HIV

in sub-Saharan Africa. Therefore, there is a need to equip health institutions with the

necessary laboratory facilities so that the CD4 test results will be provided immediately after

the test without further appointment. Providing PoC CD4 tests did not have significant effect

on decreasing loss to follow up before initiating ART and on decreasing loss to follow up

before pre-ART care. The fact that the number of studies is small and the analyses method



employed was a random effect model reduced the power, masking the effect on loss before

ART care and loss before pre-ART care. Further primary studies are needed.

Keywords

Point of care CD4 test; retention in care; systematic review; Sub-Saharan Africa

Introduction

One major barrier to tackling the Human Immuno-deficiency Virus (HIV) pandemic is diagnosing

approximately 90% of individuals who have not been tested for HIV infection.1,2,3,4

Rapid point of care

(or near-patient) testing is increasingly being used in developing world settings to improve diagnosis

of HIV infections.1,2,3,4,5

Effective care and treatment for HIV and Acquired Immuno-Deficiency Syndrome (AIDS) requires the

integration of all stages of disease management, which include: (1) HIV testing; (2) referral of those

who test HIV-positive to a clinic for assessment; (3) assessment of those patients with CD4 test to

determine eligibility for antiretroviral therapy (ART) or pre-ART care; (4) patient enrolment and

retention in pre-ART care if not immediately eligible for ART; (5) patient initiation of ART as soon as

eligible; and (6) maintenance of long-term ART adherence.6

ART involves taking a combination of antiretroviral (ARV) HIV drugs (a regimen) daily. A regimen

contains three or more ARV drugs from at least two different drug classes.7

ARV drugs prevent HIV

from multiplying and keep people with HIV healthy; but they cannot cure HIV infection or prevent HIV

transmission. In most developing countries, CD4 count is used as a criterion to determine eligibility for

ART.7 In addition, it has been demonstrated that the use of the CD4 cell count criterion is superior to

clinical staging in identifying clients eligible for ART.8 CD4 count is a laboratory test that measures the

number of CD4 T lymphocytes (CD4 cells) in a sample of blood. In people with HIV, the CD4 count is

the most important laboratory indicator of immune function and the strongest predictor of HIV

progression.7

The World Health Organization (WHO) updated guideline on antiretroviral therapy for

adults and adolescents, including pregnant women, now recommends that ART be initiated when

CD4 cell counts reach or drop below 350 cells/mm3, regardless of whether or not patients have

clinical symptoms of established disease.9 The CD4 count is also used to monitor response to ART.

7

Despite advances in the expansion of access to ART for HIV-positive patients in resource-limited

settings, two-thirds of patients in need of treatment currently do not receive it.10

Although worldwide

funding for treatment in these settings has increased and the cost of delivery of ART has decreased,

the financial sustainability of current coverage and the expansion of treatment to new patients are still

concerning.11,12,13,14

Accordingly, efforts to improve the efficiency and sustainability of ART are

increasing.15,16

Low retention of patients undermines efforts to scale up ART.17,18,19,20,21

The existing

limited evidence suggests that many patients fail to enroll in HIV care after referral from testing.2,22,23,25

One solution to this treatment gap is to integrate rapid point of care testing (PoCT) technologies,

including point of care CD4 counting into HIV counseling and testing (HCT) service sites.5 A point of

care CD4 test is a CD4 test performed in the immediate vicinity of a patient to provide a rapid same-

day result outside the conventional laboratory environment, in order to facilitate immediate clinical

decision-making, including initiation and adjustment of ART.26

These technologies allow blood

samples to be processed immediately, at the location where the HIV test is performed, so that clients



undergoing HIV counseling and testing (HCT)can receive CD4 count results on the same visit as the

HIV test.6

In addition, they are easy to use, highly automated with minimal manual steps, do not

require precise sample measurement or manipulation, and the results are easy to read. PoC

technologies do not require consistent electricity and refrigeration. The devices can operate on battery

power or an alternate power source and do not need manufacturer or specialized installation. They

also have a long shelf life for consumables; at least six months once consumables reach the facility,

meaning they can be utilized for at least six months once they are delivered to health facilities.

Furthermore, material wastes can be disposed of safely.26

Rapid testing for HIV through various methodologies, using either blood or oral fluid samples, can

give a result within 20 minutes with 97% to 100% sensitivity and specificity.5,27

Rapid point of care

testing has the potential to allow post-test counseling of those testing positive immediately after

undergoing a test, which may increase the probability of patients returning for HIV specialist care,

thus improving their health and reducing transmission.28

The effect of point of care CD4 cell count tests on retention of patients and rates of ART initiation

have been studied in some sub-Saharan African countries.14,15,17,18,29

For example, an observational

study conducted in Mozambique indicated that point of care CD4 testing enabled clinics to stage

patients promptly on-site after enrolment.14

In addition, a South African pilot study indicated that

patients offered point of care CD4 testing as part of the HCT services were more likely to visit a

referral clinic after testing.17

Another South African randomized controlled trial indicated that the

receipt of a CD4 count at the time of HIV testing increases ART initiation rates.29

However, the

findings of these studies have not yet been synthesized in the form of a systematic review. Therefore,

in this review, an attempt was made to pool evidence regarding the effect of point of care CD4 cell

count tests on retention of patients and rates of ART initiation in sub-Saharan African countries.



Objectives

To determine the effect of point of care CD4 cell count tests on retention of patients and rates of

antiretroviral therapy initiation in sub-Saharan African countries.

Types of participants

Adults (aged at least 18 years) living with HIV who were aware of their HIV zero-status.

Types of intervention(s)/phenomena of interest

Point of care CD4 testing.

Comparator

Baseline results (results before the introduction of point of care CD4 testing) or clients who were not

provided with rapid point of care CD4 tests.

Types of outcomes

The primary outcomes were: attending a wellness program, initiation of antiretroviral treatment of

enrolled patients, loss to follow-up before attending pre-ART care, loss to follow-up before ART

initiation.

Attending a wellness program means attending pre-ART care.

Successful treatment (ART) initiation is defined as documentation of dispensed antiretroviral drugs

within 60 days of a staging visit and patients were considered lost to follow-up if they did not start

treatment during this period.14,18

Alternatively it can be defined as:1) initiation of ART within 16 weeks

after HCT if they are eligible for ART based on their CD4 count or 2) arrival at the ART initiation site

within three months of CD4 testing if they are eligible for ART based on their CD4 count.29,31

Such

variances exist across different countries according to their own policies.

Types of studies

This review considered both experimental and epidemiological study designs including randomized

controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies,

prospective and retrospective cohort studies, case control studies and analytical cross sectional

studies for inclusion. Only studies conducted in sub-Saharan Africa were included.

Search strategy

The search strategy aimed to find both published and unpublished studies. A three-step search

strategy was utilized in this review. An initial limited search of MEDLINE and CINAHL was

undertaken, followed by an analysis of the text words contained in the title and abstract and of the

index terms used to describe the article. A second search using all identified keywords and index

terms was then undertaken across all included databases: MEDLINE, CINAHL, Mednar, Google

Scholar and ProQuest Dissertations and Theses.

Thirdly, the reference lists of all identified reports and articles were searched for additional studies.

Studies reported in English from 2004 to July 2013 were considered for inclusion in this review. This

date limit was chosen because significant improvements have only been made in access to ART in

low-income and middle-income countries since 2004.30



The search for unpublished studies included: Mednar, Google Scholar and ProQuest

Dissertations and Theses.

The initial search terms combined and used were: people living with HIV (for population); point of care

CD4 testing, rapid CD4 testing (for intervention); patient retention, treatment initiation, ART initiation

(for outcome) (Appendix I).

Method of the review

Papers selected for retrieval were assessed by two independent reviewers for methodological validity

prior to inclusion in the review using standardized critical appraisal instruments from the Joanna

Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI)

(Appendix II).

Data collection

Data were extracted independently by the two reviewers from papers included in the review using the

standardized data extraction tool from JBI-MAStARI (Appendix III).The data extracted included

specific details about the interventions, populations, study methods and outcomes of significance to

the review question and specific objectives. The authors of three primary studies were contacted by

email for clarity in circumstances where the information provided was incomplete. The authors of two

primary studies responded to the request and clarified the ambiguities.18,31

The other author did not

respond.32

Data synthesis

Quantitative data were pooled in statistical meta-analysis using JBI-MAStARI. All results were

subjected to double data entry. Before conducting meta-analyses, heterogeneity was assessed

statistically using the standard Chi-square and visual inspection of the meta-analysis output on a

forest plot. Because of the possibility of low power since there were few studies, a significance level of

p<0.1 was used in order to protect against the possibility of falsely stating that there was no

heterogeneity present. Data were also explored using subgroup analyses based on the different study

designs included in this review.

For the first outcome (treatment initiation), the data analyses were based on a fixed effects model.

Effect sizes expressed as risk ratios (RR) and their 95% confidence intervals were calculated using

the Mantel-Haenszel method.

Since there was heterogeneity among the studies for the other three outcomes (tested using the Chi-

square test); the data syntheses were based on a random effects model. Effect sizes expressed as

RR and their 95% confidence intervals were calculated using the DerSimonian and Laird method.



Results

Description of studies

The initial search identified 55 articles and reports (Figure 1 and Appendix IV). Four studies were

duplicates. Out of the 51 studies, a total of 11 articles were retrieved based on their titles and

abstracts (Appendix V). Forty studies were excluded because their titles and abstracts did not meet

the inclusion criteria (Appendix VI). The eleven retrieved studies were critically appraised using the

appropriate JBI-MAStARI critical appraisal tool. Eight articles were excluded during critical appraisal,

(Appendix VII). Data were extracted from the remaining three studies using the JBI-MAStARI data

extraction form (Appendix VIII).

Of the three studies included for extraction, one was a randomized controlled trial with three arms,29

and two were quasi-experimental before and after studies.31,32

Faal and colleagues conducted their study in an urban primary health care clinic (Esselen Clinic) in

the inner city of Johannesburg in South Africa.29

The study included adults above 18 years of age.

Pregnant mothers were not included in the study. Patients who had WHO stage IV clinical disease at

presentation were also excluded as they were required to start ART regardless of CD4 count.

Randomization was performed by the operator of theCD4 flow cytometry machine based at the clinic

who received blood samples for CD4 analysis. The operator did not have contact with the patients.

The three arms in the study were immediate CD4 testing, leaflet arm and normal collection. For

participants in the immediate CD4 testing arm, the results were provided immediately after testing.

For participants randomized to the leaflet arm, a leaflet which explains the HIV care pathway available

to patients in the area was given and standard collection of CD4 test results (allowing participants to

collect their test results within seven days) were followed. Participants in the normal collection arm

were allowed to collect their test results within seven days. A total of 344 adults (124 in the immediate

arm, 108 in the leaflet arm and 112 in the normal collection arm) were included. The primary

outcomes were enrollment for further care within one month (for patients in the pre-ART phase) and

enrollment within three months (for those patients in the ART phase).

Larson and colleagues conducted their study in Themba Lethu HIV clinic in an academic hospital in

the city of Johannesburg in South Africa.31

The study compared ART initiation within 16 weeks of HIV

HCT (for ART eligible patients) and attending pre-ART care (for patients in the stage of pre-ART)

between baseline and the pilot period using a retrospective record review. In the pilot period, CD4 test

results were provided on the day of HCT. The study included the data of 897 adult HIV positive

patients. Out of this, 417 patients were in the baseline period receiving standard care and 480

patients were in the pilot period provided with CD4 test results on the day of testing.

Muchedzi and colleagues utilized a quasi-experimental before and after study design to compare ART

initiation among pregnant women before and after the introduction of PoC CD4 intervention.32

The

study was conducted in 43 prevention of mother to child transmission (PMTCT) sites in Zimbabwe.

The total number of mothers in the baseline study was1210 and the total number of mothers included

in the pilot study was 1100 (Appendix IX).



Figure 1: Study selection process

Methodological quality

All of the included studies had assessed outcomes using objective criteria in a reliable way. During

the search phase, the reviewers came across studies that were available only in the form of abstracts.

After contacting the authors of one primary study enough information was obtained for the study to be

included in the review.31

Themethodological quality of all included studies was rated as good. There

was no disagreement between the primary reviewer and the secondary reviewer during critical

appraisal as to whether studies met the inclusion criteria. The three studies that reported the effect of

PoC CD4 tests on ART initiation were heterogeneous.29,31,32

Therefore, a comparison was made as to

whether there was a difference in the results of meta-analyses using a fixed effects (Figure 2) and

random effects model (Figure 3). The two models produced different results.

When one study was excluded,31

the remaining two studies became homogeneous (heterogeneity chi

square 2.03, p-value=0.15).29,32

Hence, this result was accepted. The result indicates that adult

Initial

search

identified 55

studies

Eleven studies were

retrieved

Eight were excluded during

critical appraisal

Three were

included for data

extraction

Forty studies were excluded after reading

their titles and abstracts because they did

not fulfill inclusion criteria

Four studies were excluded

because they were duplicates The abstract and titles of 51

studies were examined



patients who tested HIV positive who were provided PoC CD4 testing had increased ART initiation

(Figure 4).

Figure 2: Forest plot of the effect of providing point of care CD4 testing on ART initiation among adults living with HIV in sub-Saharan Africa using a fixed effects model

Figure 2 indicates that the three studies that reported the effect of providing point of care CD4 testing on ART initiation were heterogeneous (heterogeneity chi square 54.21, p=0.0).29,31,32 The result of this meta-analysis indicates that providing POC CD4 tests will have a significant effect on ART initiation.



Figure 3: Effect of providing PoCCD4 tests on ART initiation among adults living with HIV in sub-Saharan Africa using a random effects model

Figure 3 shows that the three studies were heterogeneous (heterogeneity chi square 54.21, P=0.0).

The result of this meta-analysis indicates that providing PoC CD4 tests does not have any effect on

increasing ART initiation.



Figure 4: Effect of point of care CD4 testing on ART initiation among adults living with HIV in sub-Saharan Africa

Figure 4 shows that the two included studies are homogeneous (heterogeneity chi square=2.03,

p=0.154).29,32

The first study, was given more weight (89.2%).32

Both studies indicated that providing

PoC CD4 tests significantly increased ART initiation (P<0.0001).



Figure 5: Effect of point of care CD4 testing on loss to ART initiation among adults living with

HIV in sub-Saharan Africa

Figure 5 indicates that the two studies that reported the effect of PoC CD4 testing on loss to follow-up

before treatment initiation were heterogeneous (heterogeneity chi square=4.89, p=0.027).29,32

Therefore, a random effects model was used for the analyses. The first study was given more weight

(60.1%).32

Muchedzi and colleagues indicated that the risk of loss to follow-up before treatment

initiation among those patients who were not provided PoC CD4 tests was 1.22 times higher than

those patients who were provided PoC CD4 tests.32

Faal and colleagues indicated that the risk of loss

to follow-up before treatment initiation among those patients who were not provided PoCCD4 tests

was 1.98 times higher when compared to those patients who were provided with PoC CD4 tests.29

Both studies favored the control (i.e. those patients who were not provided with PoC CD4 tests had

higher risk to be lost before treatment initiation when compared to those patients provided with PoC

CD4 tests). However, the overall effect was not significant (p=0.107).



Figure 6: Effect of point of care CD4 testing on pre-ART care among adults living with HIV in sub-Saharan Africa

Figure 6 shows that the two studies that reported the effect of providing point of care CD4 tests on

attendance of a wellness program (pre-ART care) were homogenous (heterogeneity chi square=0.01,

p=1.0).29,31

The second study was given more weight (50.24%).29

In both studies, providing PoC CD4

tests did not have any effect on increasing the risk of attending a wellness program.



Figure 7: Effect of point of care CD4 testing on loss to pre-ART care among adults living with HIV in sub-Saharan Africa

Figure 7 indicates that the two studies that reported the effect of providing PoC CD4 tests on loss to

follow-up from pre-ART care were heterogeneous (heterogeneity chi square=55.87, p=0.0).29,32

The

first study indicated that the risk of loss to follow-up among patients who did not receive PoC CD4

tests was 2.57 times higher when compared to those patients who received PoC CD4 tests.32

In the

second study, providing PoC CD4 tests did not have any effect on the risk of loss to follow-up from

pre-ART care.29

Overall providing PoC CD4 tests did not reduce the risk of loss to follow-up before

pre-ART care (p=0.322).



Discussion

Summary of main results

This review indicated that providing point of care CD4 tests had a significant effect on increasing the

risk of treatment initiation among adults living with HIV in sub-Saharan Africa. Providing PoC CD4

tests had no significant effect on decreasing the risk of loss to follow-up before treatment initiation. In

addition, providing PoC CD4 tests had no effect on the risk of loss to follow-up from pre-ART care

(from a wellness program) or the risk of attendance of wellness programs (pre-ART care).

Overall completeness and applicability of evidence

The review has included only three studies.

Overall the effect of providing point of care CD4 tests was associated with significantly improved risk

of treatment initiation. Both included studies showed significant positive effects of point of care CD4

testing on treatment initiation.29,32

The pooled effect was also significant. One of the included studies

was a randomized trial,29

and the second study was a quasi-experimental before and after study

design.32

On the other hand, providing point of care CD4 tests did not have any effect on the risk of loss to

follow-up before treatment initiation. Each of the two studies showed that providing point of care CD4

tests reduced the risk of loss to follow-up before ART initiation.29,32

Since the heterogeneity test was

significant, a random effects model was used for analysis. The pooled effect was not significant. The

random effects model used in the analysis reduced the power of the analysis and masked the

significant effect.

Providing point of care CD4 tests did not have any effect on the risk of attending a wellness program

(pre-ART care). Each of the two included studies indicated that providing point of care CD4 tests did

not have any effect on increasing attendance of a wellness program.29,31

Similarly, the meta-analysis

result (using a fixed effects model) indicated that there was no pooled effect of providing PoC CD4

tests on the risk of attending a wellness program.

Two studies reported the effect of providing point of care CD4 tests on the risk of loss to follow-up

from pre-ART care.29,32

One of the studies included in this analysis demonstrated significant effect of

point of care CD4 testing on decreasing the risk of loss to follow-up from pre-ART care.32

The other

study showed that providing PoC CD4 tests does not have any effect on decreasing the risk of loss to

follow-up from pre-ART care.29

The meta-analysis result (using a random effects model) indicated that

providing point of care CD4 tests did not have a significant effect on reducing the risk of loss to follow-

up from pre-ART care. The random effects model used in the analysis reduced the power of the

analysis and masked the significant effect.

Results were pooled using a fixed effects model for two outcomes (ART initiation and attending a

wellness program). However, a random effects model was used for the remaining two outcomes (loss

before ART care and loss before pre-ART care). The small number of studies included in this review

and the fact that a random effects model was used for pooling results on these outcomes (loss before

ART care and loss before pre-ART care) reduced the power of analyses. Therefore, the results

should be interpreted with caution.



Quality of the evidence

All of the findings were pooled from one randomized controlled trial and two quasi-experimental

studies. Hence, the findings can be graded as a JBI level of evidence 1.b.33

Conclusion

The review of primary studies conducted from 2004 to 2013 indicated that providing point of care CD4

tests had a significant effect on increasing ART initiation among adults living with HIV in sub-Saharan

Africa. However, providing PoC CD4 tests did not have an effect on increasing attendance of pre-ART

care.

The intervention did not have a significant effect on decreasing loss to follow-up before initiating ART.

Providing PoC CD4 tests did not have an effect on decreasing loss to follow-up before pre-ART care.

This needs further investigation. The scarcity of studies conducted in the area and the fact that a

random effects model was utilized for pooling the results of a small number of studies, limits the

conclusion that PoC CD4 testing has no effect on decreasing loss to follow-up before ART initiation or

on decreasing loss to follow-up from pre-ART care. More studies are required.

Implications for practice

Providing point of care CD4 tests had a significant effect on increasing ART initiation. Therefore, there

is a need to equip health institutions with the necessary laboratory facilities so that the CD4 test

results will be provided immediately after the test without further appointment. The provision of PoC

CD4 tests can improve ART initiation, although it cannot improve the risk of attendance of pre-ART

care.

Implications for research

The current evidence indicated that providing point of care CD4 tests did not have any effect on loss

to follow-up before treatment initiation. This review also indicated that providing point of care CD4

tests did not have any effect on loss to follow-up before pre-ART care.

However, the fact that the number of studies is small and the analysis method employed was a

random effects model reduced the power, masking the effect on the two outcomes (loss to follow-up

before ART care and loss to follow-up before pre-ART care). Therefore, further primary studies need

to be conducted on the area.

As well, primary studies (preferably randomized controlled trials) that address the effect of providing

point of care CD4 tests on time to treatment initiation and on the success of referral will be important

for informing evidence based practice.

Contributions of authors

GTF has contributed to the development of the protocol, searching for studies, study selection,

appraisal of selected studies, data extraction, meta-analysis and preparation of the final report.

TDD has contributed to the development of the protocol, searching for studies, study selection,

appraisal of selected studies, data extraction and preparation of the final report.

Conflict of interest

We declare neither financial nor intellectual conflict of interest in this work.



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http://europepmc.org/search;jsessionid=8ZyKoWUxJMQ7rwYHxy4i.56?page=1&query=AUTH:%22Lele+S%22

http://www.aidsinfonet.org/

http://www.ncbi.nlm.nih.gov/pubmed?term=Carter%20RJ%5BAuthor%5D&cauthor=true&cauthor_uid=20595905

http://www.ncbi.nlm.nih.gov/pubmed?term=Dugan%20K%5BAuthor%5D&cauthor=true&cauthor_uid=20595905

http://www.ncbi.nlm.nih.gov/pubmed?term=El-Sadr%20WM%5BAuthor%5D&cauthor=true&cauthor_uid=20595905

http://www.ncbi.nlm.nih.gov/pubmed?term=Myer%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20595905

http://www.ncbi.nlm.nih.gov/pubmed?term=Otieno%20J%5BAuthor%5D&cauthor=true&cauthor_uid=20595905

http://www.ncbi.nlm.nih.gov/pubmed?term=Pungpapong%20N%5BAuthor%5D&cauthor=true&cauthor_uid=20595905

http://www.unicef.org/eapro/Towards%20Universal%20Access%20on%20HIVAIDS.pdf

http://www.unicef.org/eapro/Towards%20Universal%20Access%20on%20HIVAIDS.pdf

http://www.ncbi.nlm.nih.gov/pubmed?term=Greenwald%20JL%5BAuthor%5D&cauthor=true&cauthor_uid=16524549

http://www.ncbi.nlm.nih.gov/pubmed?term=Burstein%20GR%5BAuthor%5D&cauthor=true&cauthor_uid=16524549

http://www.ncbi.nlm.nih.gov/pubmed?term=Pincus%20J%5BAuthor%5D&cauthor=true&cauthor_uid=16524549

http://www.ncbi.nlm.nih.gov/pubmed?term=Branson%20B%5BAuthor%5D&cauthor=true&cauthor_uid=16524549



Experience with rapid and standard serologic testing. Ann Emerg Med.1999;33:147-154.

17. Larson B, Schnippel K, Ndibongo B, Xulu T. Brenan A, Long L. et al. Rapid, point-of-care CD4 testing at mobile and fixed HIV testing sites: Does it increase linkage to HIV care? Johannesburg: HE2RO Policy Brief. Health Economics and Epidemiology Research Office.2011;(3).

18. Larson BA, Schnippel K, Ndibongo B, Xulu T, Brenan A, Long L, et al. Rapid Point of Care CD4 Testing at Mobile HIV Testing Sites to Increase Linkage to Care: An Evaluation of a Pilot Program in South Africa. J Acquir Immune Defic Syndr.2012;61(2):e13-e17.

19. Lawn SD, Myer L, Harling G, Orrell C, Bekker LG, Wood R. Determinants of mortality and non death losses from an antiretroviral treatment service in South Africa: implications for program evaluation. Clin Infect Dis.2006;43(6):770-76.

20. McCoy D, Chand S, Sridhar D. Global health funding: how much, where it comes from and where it goes. Health Policy.2009;24:407-17.

21. Perez-Then E, Pena R, Tavarez-Rojas M, Pena C, Quinonez S, Buttler M, et al. Preventing mother-to-child HIV transmission in a developing country: The Dominican Republic experience. J Acquir Immune Defic Syndr.2003;34(5):506-511.

22. UNAIDS. UNAIDS Update on the Global AIDS Epidemic.2010.

23. Wools-Kaloustian K, Kimaiyo S, Diero L, Sika A, Sidle J, YiannoutsosCT, et al. Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya. AIDS.2006;2:41-48.

24. van Oosterhout JJ, Bodasing N, Kumwenda JJ, NyIrenda CC, Mallewa J, Cleary PR, et al. Evaluation of antiretroviral therapy results in a resource-poor setting in Blantyre, Malawi. Trop Med Int Health.2005;10(5):464-70.

25. Ravishankar N, Gubbins P, Cooley RJ, Leach-kemon K, Michuad CM, Jamison DT, et al. Financing of global health: tracking development assistance for health from 1990 to 2007. Lancet.2009;373:2113-24.

26. The Ethiopian Health and Nutrition Research Institute. Guidelines for the Implementation of Point-Of-Care CD4 Testing Technologies in Ethiopia, January 2013 available at:http://www.ehnri.gov.et/CD4%20Implementation%20Guidelines.pdf (accessed April 28, 2013).

27. Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med.2011; 8: e1001056.

28. UNAIDS. UNAIDS Outlook Report 2010. 2010.

29. Faal M, Naidoo N, Glencross DK, Venter WDF, OsihR.Providing Immediate CD4 Count Results at HIV Testing Improves ART Initiation. J Acquir Immune Defic Syndr.2011;58(3):e54–e59.

30. UNAIDS-WHO. Scaling up access to antiretroviral therapy in low and middle-income countries: Global and regional progress in 2008. UNAIDS-WHO Geneva.Latest UNAIDS estimate of cART coverage in low-income and middle-income Countries,2009.

31. Larson BA, Schnippel K, Brennan A, Long L,Xulu T, Maotoe T, et al. Same-Day CD4 Testing to Improve Uptake of HIV Care and Treatment in South Africa: Point of Care Is Not Enough. AIDS Research and Treatment.2013 2013;2013:94149.

32. Muchedzi A, Chadambuka A, ChikwinyaB,Mahomva A. Evaluating the effect of the use of Point of Care CD4 machines on access to antiretroviral therapy (ART) eligibility screening and ART initiation for HIV-positive pregnant women in Zimbabwe: towards elimination of new paediatric HIV infection by 2015. Journal of the International AIDS Society.2012;15(suppl 3):282.

http://www.ehnri.gov.et/CD4%20Implementation%20Guidelines.pdf



33. http://joannabriggs.org/jbi-approach.html#tabbed-nav=Levels-of-Evidence accessed on March 11, 2014.

http://joannabriggs.org/jbi-approach.html#tabbed-nav=Levels-of-Evidence



Appendix I: Search strategy

Domain Description Search terms

Participants People living with HIV

People living with HIV

Intervention Point of care CD4 testing

point of care CD4 testing, rapid CD4 testing, CD4 staging

Comparator Baseline or control

No search term was used

Outcome Adherence to ART, treatment initiation

patient retention or treatment initiation or ART initiation

For example, the initial search terms used for searching articles in MEDLINE were combined as

follows: ((People living with HIV) and (Point of care CD4 testing) or (rapid cd4 testing) and (patient

retention) or (treatment initiation) or (ART initiation) or (CD4 staging))

(((((Topic= ("point of care") OR Topic= (point of care CD4 TESTING)) OR (Topic= (rapid CD4 testing))

AND Topic= ((patient retention))) OR Topic= (ART INITIATION)) OR Topic= (treatment INITIATION))

OR (Topic=(CD4 STAGING)) AND Topic=((HIV)))

Time span=2004-2013. Databases=MEDLINE.

Later the key words of the studies found during the initial search were utilized for the subsequent

manual search. These search terms included: CD4 monitoring, loss to initiation, point of care

diagnostics, pre-ART loss to care, point of care CD4, retention in care, antiretroviral adherence,

cascade of care, HIV testing and linkage to care. They were combined as follows: (HIV testing or

point-of-care diagnostics or point-of-care CD4) and (loss to initiation or pre-ART loss to care or

retention in care or antiretroviral adherence or cascade of care or linkage to care).



Appendix II: Appraisal instruments

Insert page bre



Appendix III: Data extraction instruments





Appendix IV: Search results 1. Amuron B, Namara G, Birungi J, Nabiryo C, Levin J, Grosskurth H, et al. Mortality and loss-to-

follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda. BMC Public Health.2009; 9(290):1471-2458.

2. Baloyi GR. Loss to initiation on antiretroviral therapy (ART) after voluntary counselling and testing (VCT). Thesis ((MSc(Med)(Pharmacy))--University of Limpopo (Medunsa Campus), http://hdl.handle.net/10386/506.2011.

3. Bassett IV, Wang B, Chetty S, Mazibuko M, Bearnot B, Giddy J, et al. Loss to care and death before antiretroviral therapy in Durban, South Africa. J Acquir Immune Defic Syndr.2009; 51(2):135-9.

4. Battala M, Sebastian M, Bachani D, Sogarwal R, Sarna A. Factors affecting access to and enrolment in art services in india: findings from qualitative data. AIDS 2012:XIX International AIDS Conference, Washington DC.2012

5. Nwuba CO, Dagunduro T, Umenyi C, Peters B, Afolayan F, Abolarin OA. Laboratory-based approach to reduce loss to follow-up of HIV-positive clients. Journal of the International AIDS Society.2012;15(Suppl 3):246.

6. Chamie G, Kwarisiima D, Kabami J, Clark TD, Jain V, Black D, et al. Community-based HIV Testing and point of care CD4 in Rural Uganda: Outcomes in a Routine Linkage to Care Strategy and an Enhanced Strategy with Accelerated ART Start. Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, WA, USA.2012.

7. Clouse K, Pettifor AE, Maskew M, Bassett J, Van Rie A, Behets F, et al. Patient retention from HIV diagnosis through one year on antiretroviral therapy at a primary health care clinic in Johannesburg, South Africa. J Acquir Immune Defic Syndr.2013; 62(2):e39-46.

8. Clouse K, Pettifor A, Shearer K, Maskew M, Bassett J, Larson B, et al. Loss to follow-up before and after delivery among women testing HIV positive during pregnancy in Johannesburg, South Africa. Trop Med Int Health.2013;18(4):451-60.

9. Duncombe C, Ball A, Passarelli C, Hirnschall G. Treatment 2.0: catalyzing the next phase of treatment, care and support. CurrOpin HIV AIDS.2013;8(1):4-11.

10. Faal M, Naidoo N,Glencross DK, Venter WD, OsihR.Providing Immediate CD4 Count Results at HIV Testing Improves ART Initiation. J Acquir Immune Defic Syndr.2011;58(3): 344-52.

11. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic review. Trop Med Int Health.2010;1: 1-15.

12. GordonMS, Kinlock TW, McKenzie M, Wilson ME, Rich JD. Rapid HIV Testing forIndividuals on Probation/Parole: Outcomes of an Intervention Trial. AIDS Behav.2013;17(6):2022-30.

13. Govindasamy D, van Schaik N, Kranzer K, Wood R, Mathews C, Bekker LG. Linkages to HIV care from a mobile testing unit in South Africa by different CD4 count strata. J Acquir Immune Defic Syndr.2011;58(3): 344-52.

14. Granich R, Gupta S, Suthar AB, Smyth C, Hoos D, Vitoria M, et al. Antiretroviral therapy in prevention of HIV and TB: update on current research efforts. Curr HIV Res.2011;9(6):446-69.

15. Guenter D, Greer J, Barbara A, Robinson G, Roberts J, Browne G. Rapid point of care HIV testing in community-based anonymous testing program: a valuable alternative to conventional testing. AIDS Patient Care STDS.2008;22(3):195-204.



16. Harries AD, Zachariah R, Lawn SD, Rosen S. Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa. Trop Med Int Health.2010;1:70-5.

17. Herbert S, Edwards S, Carrick G, Copas A, Sandford C, Amphlett M, et al. Evaluation of PIMA point of care CD4 testing in a large UK HIV service. Sexually Transmitted Infections.2012;88(6):413-417.

18. Jani IV, Sitoe NE, Alfai ER, Chongo PL, Quevedo JI, Rocha BM, et al. Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet.2011;378:1572-79.

19. Johnson MO, Chesney MA, Neilands TB, Dilworth SE, Remien RH, Weinhardt LS, et al. Disparities in reported reasons for not initiating or stopping antiretroviral treatment among a diverse sample of persons living with HIV. J Gen Intern Med.2009;24(2):247-51.

20. Kahenya GC. Challenges of scaling up laboratory services for diagnosis and monitoring tests of HIV/AIDS patients on antiretroviral therapy in Zambia. Thesis (MPH) --University of Limpopo, http://hdl.handle.net/10386/650.2009.

21. Kalichman SC, Cherry C, Kalichman MO, Amaral CM, White D, Pope H, et al. Integrated behavioral intervention to improve HIV/AIDS treatment adherence and reduce HIV transmission. Am J Public Health.2011;101(3):531-8.

22. Kassler WJ, Alwano-Edyegu MG, Marum E, Biryahwaho B, Kataaha P, Dillon B. Rapid HIV testing with same-day results: a field trial in Uganda. Int J STD AIDS.1998;9(3):134-8.

23. Kilmarx PH, Mutasa-Apollo T. Patching a leaky pipe: the cascade of HIV care. Current Opinion in HIV and AIDS.2013;8(1):59-64.

24. Lamb MR, El-Sadr WM, Geng E, Nash D. Association of Adherence Support and Outreach Services with Total Attrition, Loss to Follow-Up, and Death among ART Patients in Sub-Saharan Africa. PLoS.2012;7(6):e38443.

25. Larson BA, Schnippel K, Ndibongo B, Xulu T, Brenan A, Long L, et al. Rapid Point of Care CD4 Testing at Mobile HIV Testing Sites to Increase Linkage to Care: An Evaluation of a Pilot Program in South Africa. J Acquir Immune Defic Syndr.2012; 61(2): e13-e17.

26. Larson BA, Schnippel K, Ndibongo B, Xulu T, Brenan A, Long L, et al. Rapid, point of care CD4 testing at mobile and fixed HIV testing sites: Does it increase linkage to HIV care? Johannesburg: HE2RO Policy Brief. Health Economics and Epidemiology Research Office.2011;(3).

27. Larson BA, Schnippel K, Brennan A, Long L,Xulu T, Maotoe T, et al. Same-Day CD4 Testing to Improve Uptake of HIV Care and Treatment in South Africa: Point of Care Is Not Enough. AIDS Research and Treatment.2013;2013:94149.

28. Lessells RJ, Mutevedzi PC, Cooke GS, Newell ML. Retention in HIV care for individuals not yet eligible for antiretroviral therapy: rural KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr.2011;56(3):e79-e86.

29. McGrath N, Glynn JR, Saul J, Kranzer K, Jahn A, Mwaungulu F, et al. What happens to ART-eligible patients who do not start ART? Dropout between screening and ART initiation: a cohort study in Karonga, Malawi. BMC Public Health.2010;10(601):1471-2458.

30. McNairy ML, Cohen M, El-Sadr WM. Antiretroviral therapy for prevention is a combination strategy. Curr HIV/AIDS Rep.2013;10(2):152-8.



31. Micek MA, Gimbel-Sherr K, Baptista AJ, Matediana E, Montoya P, Pfeiffer J, et al. Loss to follow-up of adults in public HIV care systems in central Mozambique: identifying obstacles to treatment. J Acquir Immune Defic Syndr.2009; 52(3):397-405.

32. Mills, EJ, Ford N. Home-based HIV counseling and testing as a gateway to earlier initiation of antiretroviral therapy.Clin Infect Dis.2012;54: 282–284.

33. Molesworth AM, Ndhlovu R, Banda E, Saul J, Ngwira B, Glynn JR, et al. High accuracy of home-based community rapid HIV testing in rural Malawi. J Acquir Immune Defic Syndr.2010;55(5):625-30.

34. Muchedzi A, Chadambuka A, Chikwinya B, Mahomva A. Evaluating the effect of the use of Point of Care CD4 machines on access to antiretroviral therapy (ART) eligibility screening and ART initiation for HIV-positive pregnant women in Zimbabwe: towards elimination of new paediatric HIV infection by 2015. Journal of the International AIDS Society.2012;15(suppl 3):282.

35. Mugglin C, Estill J, Wandeler G, Bender N, Egger M, Gsponer T, et al. Linkage to care from HIV diagnosis to antiretroviral therapy in sub-Saharan Africa: Systematic review and meta-analysis. International epidemiological Databases to Evaluate AIDS (IeDEA) Southern Africa, .2011 [Access Date: June 08, 2013].

36. Mugglin C, Estill J, Wandeler G, Bender N, Egger M, Gsponer T, et al.Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis. Tropical Medicine & International Health.2012;17(12): 1509-1520.

37. Sekandi, JN, SempeeraH, List J, Mugerwa MA, Asiimwe S, Yin X, et al. High acceptance of home-based HIV counseling and testing in an urban community setting in Uganda. BMC Public Health C7 - 730.2011;11(1):1-8.

38. TobaiwaO, Bollinger T,Sitoe N, Lehe J, Peter T, Jani I, et al. Implementation of a wireless GPRS-based monitoring system for point of care CD4 testing at rural primary health facilities in Mozambique. Journal of the International AIDS Society.2012;15(Suppl 3):244-245.

39. Ocero AA. Retention of HIV positive person at antiretroviral therapy clinics in post-conflict Northern Uganda. Thesis (MPH)--University of Limpopo, http://hdl.handle.net/10386/223.2009.

40. Olender S, Wilkin TJ, Taylor SB, Hammer SM. Advances in Antiretroviral Therapy. Top Antivir Med.2012;20(2):61-86.

41. Rosen S, Fox MP. Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review. PLoS Med.2011;8(7):e1001056.

42. Sabapathy K, Van den Bergh R, Fidler S, Hayes R, Ford N. Home based voluntary HIV testing in sub-Saharan Africa:a systematic review and meta analysis. AIDS 2012:XIX International AIDS Conference, Washington DC.2012.

43. Sukapirom K, Onlamoon N, Thepthai C, Polsrila K, Tassaneetrithep B, Pattanapanyasat K. Performance evaluation of the Alere PIMA CD4 test for monitoring HIV-infected individuals in resource-constrained settings. J Acquir Immune Defic Syndr.2011; 58(2): 141-7.

44. To SW, Chen JH, Yam W. Current assays for HIV-1 diagnostics and antiretroviral therapy monitoring: challenges and possibilities. Future Virology.2013; 8(4): 405-419.

45. Siedner MJ, Lankowski A, Haberer JE, Kembabazi A, Emenyonu N, Tsai AC, et al. Rethinking the “Pre” in Pre-Therapy Counseling: No Benefit of Additional Visits Prior to Therapy on Adherence or Viremia in Ugandans Initiating ARVs. PLoS ONE.2012;7(6): e39894.



46. Smart T. Point of care (PoC) diagnostics are essential to achieving an AIDS-free generation and improving outcomes in HIV-exposed children. HIV & AIDS Treatment in Practice.2012; (200):2-12.

47. Varughese JK, Rosenberg MG, Kim K. HIV in the tropics: staging in the resource-limited setting. CurrOpin Infect Dis.2012;25(5):477-83.

48. Veres A, Dryden-Peterson S, van Widenfelt E, Motshegwa P, Mine M, Moyo S, et al. An automated platform for delivery of CD4 results to SMSenabled antenatal clinic printers, Botswana. Journal of the International AIDS Society.2012;15(Suppl 3):244.

49. Zungu LM. An evaluation of determinants of adherence to antiretroviral therapy in AIDS patients in GertSibande District, Mpumalanga Province, Med dissertation. University of Pretoria, http://upetd.up.ac.za/thesis/available/etd-08042010-140153/E10/263/gm.2009.

50. Vanschaik N, Kranzer K, Wood R, Bekker LG. Earlier HIV diagnosis--are mobile services the answer. S Afr Med J.2010;100(10):671-4.

51. Van Rooyen H, Barnabas RV, Baeten JM, Phakati, Z,Joseph P. High HIV testing uptake and linkage to care in a novel program of home based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune DeficSyndr.2013;64(1):e1-e8.



Appendix V: Studies selected for retrieval 1. Baloyi GR. Loss to initiation on antiretroviral therapy (ART) after voluntary counselling and

testing (VCT). Thesis ((MSc(Med)(Pharmacy))--University of Limpopo (Medunsa Campus), http://hdl.handle.net/10386/506.2011.

2. Nwuba CO, Dagunduro T, Umenyi C, Peters B, Afolayan F, Abolarin OA.Laboratory-based approach to reduce loss to follow-up of HIV-positive clients. Journal of the International AIDS Society.2012;15(Suppl 3): 246.

3. Chamie G, Kwarisiima D, Kabami J, Clark TD, Jain V, Black D, et al. Community-based HIV Testing and point of care CD4 in Rural Uganda: Outcomes in a Routine Linkage to Care Strategy and an Enhanced Strategy with Accelerated ART Start. Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, WA, USA.2012.

4. Faal M, Naidoo N,Glencross DK, Venter WD, Osih R. Providing Immediate CD4 Count Results at HIV Testing Improves ART Initiation. J Acquir Immune Defic Syndr.2011;58(3): 344-52.

5. Jani IV, Sitoe NE, Alfai ER, Chongo PL, Quevedo JI, Rocha BM, et al. Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet.2011;378:1572-79.

6. Lamb MR, El-Sadr WM, Geng E, Nash D. Association of Adherence Support and Outreach Services with Total Attrition, Loss to Follow-Up, and Death among ART Patients in Sub-Saharan Africa. PLoS.2012;7(6):e38443.

7. Larson BA, Schnippel K, Ndibongo B, Xulu T, Brenan A, Long L, et al. Rapid Point of Care CD4 Testing at Mobile HIV Testing Sites to Increase Linkage to Care: An Evaluation of a Pilot Program in South Africa. J Acquir Immune Defic Syndr.2012; 61(2): e13-e17.

8. Larson BA, Schnippel K, Brennan A, Long L,Xulu T, Maotoe T, et al. Same-Day CD4 Testing to Improve Uptake of HIV Care and Treatment in South Africa: Point of Care Is Not Enough. AIDS Research and Treatment.2013.2013:;2013:94149.

9. Muchedzi A, Chadambuka A, Chikwinya B, Mahomva A. Evaluating the effect of the use of Point of Care CD4 machines on access to antiretroviral therapy (ART) eligibility screening and ART initiation for HIV-positive pregnant women in Zimbabwe: towards elimination of new paediatric HIV infection by 2015. Journal of the International AIDS Society.2012;15(Suppl 3):282.

10. TobaiwaO, Bollinger T,Sitoe N, Lehe J, Peter T, Jani I, et al. Implementation of a wireless GPRS-based monitoring system for point of care CD4 testing at rural primary health facilities in Mozambique. Journal of the International AIDS Society.2012;15(Suppl 3):244-245.

11. Van Rooyen H, Barnabas RV, Baeten JM, PhakatiZ,Joseph P. High HIV testing uptake and linkage to care in a novel program of home based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune DeficSyndr. 2013;64(1):e1-e8.



Appendix VI: Studies not selected for retrieval

1. Amuron B, Namara G, Birungi J, Nabiryo C, Levin J, Grosskurth H, et al. Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda. BMC Public Health.2009; 9(290): 1471-2458.

2. Bassett IV, Wang B, Chetty S, Mazibuko M, Bearnot B, Giddy J, et al. Loss to care and death before antiretroviral therapy in Durban, South Africa. J Acquir Immune Defic Syndr.2009; 51(2):135-9.

3. Battala M, Sebastian M, Bachani D, Sogarwal R, Sarna A. Factors affecting access to and enrolment in art services in india: findings from qualitative data. AIDS 2012:XIX International AIDS Conference, Washington DC.2012.

4. Clouse K, Pettifor AE, Maskew M, Bassett J, Van Rie A, Behets F, et al. Patient retention from HIV diagnosis through one year on antiretroviral therapy at a primary health care clinic in Johannesburg, South Africa. J Acquir Immune Defic Syndr.2013; 62(2):e39-46.

5. Clouse K, Pettifor A, Shearer K, Maskew M, Bassett J, Larson B, et al. Loss to follow-up before and after delivery among women testing HIV positive during pregnancy in Johannesburg, South Africa. Trop Med Int Health.2013;18(4):451-60.

6. Duncombe C, Ball A, Passarelli C, Hirnschall G. Treatment 2.0: catalyzing the next phase of treatment, care and support.CurrOpin HIV AIDS.2013;8(1):4-11.

7. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic review. Trop Med Int Health.2010;1: 1-15.

8. GordonMS, Kinlock TW, McKenzie M, Wilson ME, Rich JD. Rapid HIV Testing forIndividuals on Probation/Parole: Outcomes of an Intervention Trial. AIDS Behav.2013;17(6):2022-30.

9. Govindasamy D, van Schaik N, Kranzer K, Wood R, Mathews C, Bekker LG. Linkages to HIV care from a mobile testing unit in South Africa by different CD4 count strata. J Acquir Immune Defic Syndr.2011;58(3): 344-52.

10. Granich R, Gupta S, Suthar AB, Smyth C, Hoos D, Vitoria M, et al. Antiretroviral therapy in prevention of HIV and TB: update on current research efforts. Curr HIV Res.2011;9(6):446-69.

11. Guenter D, Greer J, Barbara A, Robinson G, Roberts J, Browne G. Rapid point of care HIV testing in community-based anonymous testing program: a valuable alternative to conventional testing. AIDS Patient Care STDS.2008;22(3):195-204.

12. HarriesAD, Zachariah R, Lawn SD, Rosen S. Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa. Trop Med Int Health.2010;1:70-5.

13. Herbert S, Edwards S, Carrick G, Copas A, Sandford C, Amphlett M, et al. Evaluation of PIMA point of care CD4 testing in a large UK HIV service. Sexually Transmitted Infections.2012;88(6):413-417.

14. Johnson MO, Chesney MA, Neilands TB, Dilworth SE, Remien RH, Weinhardt LS, et al. Disparities in reported reasons for not initiating or stopping antiretroviral treatment among a diverse sample of persons living with HIV. J Gen Intern Med.2009;24(2):247-51.

15. Kahenya GC. Challenges of scaling up laboratory services for diagnosis and monitoring tests of HIV/AIDS patients on antiretroviral therapy in Zambia. Thesis (MPH) --University of Limpopo, http://hdl.handle.net/10386/650.2009.



16. Kalichman SC, Cherry C, Kalichman MO, Amaral CM, White D, Pope H, et al. Integrated behavioral intervention to improve HIV/AIDS treatment adherence and reduce HIV transmission. Am J Public Health.2011;101(3):531-8.

17. Kassler WJ, Alwano-Edyegu MG, Marum E, Biryahwaho B, Kataaha P, Dillon B. Rapid HIV testing with same-day results: a field trial in Uganda. Int J STD AIDS.1998;9(3):134-8.

18. Kilmarx PH, Mutasa-Apollo T. Patching a leaky pipe: the cascade of HIV care. Current Opinion in HIV and AIDS.2013;8(1):59-64.

19. Larson BA, Schnippel K, Ndibongo B, Xulu T, Brenan A, Long L, et al. Rapid, point of care CD4 testing at mobile and fixed HIV testing sites: Does it increase linkage to HIV care? Johannesburg: HE2RO Policy Brief. Health Economics and Epidemiology Research Office.2011; (3).

20. Lessells RJ, Mutevedzi PC, Cooke GS, Newell ML. Retention in HIV care for individuals not yet eligible for antiretroviral therapy: rural KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr.2011;56(3):e79-e86.

21. McGrath N, Glynn JR, Saul J, Kranzer K, Jahn A, Mwaungulu F, et al. What happens to ART-eligible patients who do not start ART? Dropout between screening and ART initiation: a cohort study in Karonga, Malawi. BMC Public Health.2010; 10(601):1471-2458.

22. McNairy ML, Cohen M, El-Sadr WM. Antiretroviral therapy for prevention is a combination strategy. Curr HIV/AIDS Rep.2013;10(2):152-8.

23. Micek MA, Gimbel-Sherr K, Baptista AJ, Matediana E, Montoya P, Pfeiffer J, et al. Loss to follow-up of adults in public HIV care systems in central Mozambique: identifying obstacles to treatment. J Acquir Immune Defic Syndr.2009; 52(3): 397-405.

24. Mills, EJ, Ford N. Home-based HIV counseling and testing as a gateway to earlier initiation of antiretroviral therapy.Clin Infect Dis.2012;54: 282–284.

25. Molesworth AM, Ndhlovu R, Banda E, Saul J, Ngwira B, Glynn JR, et al. High accuracy of home-based community rapid HIV testing in rural Malawi. J Acquir Immune Defic Syndr.2010;55(5):625-30.

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Appendix VII: Excluded studies

MAStARI

Baloyi GR. Loss to initiation on antiretroviral therapy (ART) after voluntary counseling and testing (VCT)

Reason for exclusion: Intervention of interest is multiple.

Nwuba CO, Dagunduro T, Umenyi C, Peters B, Afolayan F, Abolarin O. A laboratory-based approach to reduce loss to follow-up of HIV-positive clients

Reason for exclusion: The intervention mechanism is not compatible with the objective of our study.

Chamie G, Kwarisiima D, Kabami J, Clark TD, Jain V, Black D, et al. Community-based HIV Testing and Point of Care CD4 in Rural Uganda: Outcomes in a Routine Linkage to Care Strategy and an Enhanced Strategy with Accelerated ART Start

Reason for exclusion: The intervention does not meet inclusion criteria.

Lamb MR, El-Sadr WM, Geng E, Nash D. Association of Adherence Support and Outreach Services with Total Attrition, Loss to Follow-Up, and Death among ART Patients in Sub-Saharan Africa

Reason for exclusion: The intervention of interest is different from ours.

TobaiwaO, Bollinger T,Sitoe N, Lehe J, Peter T, Jani I, et al. Implementation of a wireless GPRS-based monitoring system for point of care CD4 testing at rural primary health facilities in Mozambique

Reason for exclusion: Thestudy outcome is not in agreement with our research question

Van Rooyen H, Barnabas RV, Baeten JM, Phakati Z,Joseph P. High HIV testing uptake and linkage to care in a novel program of home based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa

Reason for exclusion: The intervention does not meet inclusion criteria.

Jani IV, Sitoe NE, Alfai ER, Chongo PL, Quevedo JI, Rocha BM, et al. Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study

Reason for exclusion: The study population also included HIV patients less than 15 years of age.

Larson BA, Schnippel K, Ndibongo B, Xulu T, Brenan A, Long L, et al. Rapid Point of Care CD4 Testing at Mobile HIV Testing Sites to Increase Linkage to Care: An Evaluation of a Pilot Program in South Africa

Reason for exclusion: The outcomes we are interested are not reported in the study.



Appendix VIII: Included studies

MAStARI

Study Methods Participants Intervention A Intervention B

Notes

Faal M, Naidoo N, Glencross DK, Venter WD, Osih R, 2011

Randomized three arm trial

HIV positive adults who were not pregnant

Standard care (standard collection and leaflet arms)

Immediate CD4 test

The study was conducted with three arms

Larson BA, Schnippel K, Brennan A, Long L, Xulu T, Maotoe T, et al, 2013

Quasi-experimental before and after study design

Adult HIV positive patients

Standard care/Baseline

PoC CD4 testing

The study clearly stated the intervention & outcomes

Muchedzi A, Chadambuka A, Chikwinya B, Mahomva A, 2012


HIV positive pregnant women

Baseline PoC CD4 testing

The intervention & outcome are clearly stated



Appendix IX: List of study findings/conclusions

Study Purpose Design Participants

Data collection methods

Setting Country Analyses

Faal M, Naidoo N, Glencross DK, Venter WD, Osih R, 2011

To evaluate the impact of a CD4 count result and patient written information provided immediately after diagnoses on retention in care

Randomized three- arm trial

344 HIV positive adults (124 in the immediate arm, 108 in the leaf let arm and 112 in the NC arm) who were not pregnant and whose WHO clinical staging was less than 4

Prospectively through monitoring and follow-up

Urban primary health care clinic (Esselen clinic), serving a densely populated and industrialized catchment area and found in Johannesburg

South Africa

X2

test and risk ratio analyses for primary outcome (proportion of patients reporting for further care) , wilcoxon rank sum analyses for secondary outcome (effect of intervention on time from HIV testing to various end points), univariate analyses, multivariate logistic regression assisted by likelihood ratio test)

Larson BA, Schnippel K, Brennan A, Long L, Xulu T,

To evaluate whether a pilot program providing PoCCD4 tests


897 adult HIV positive patients (417 in the baseline and 480 in

Retrospective record review

Themba Lethu Clinic (comprehensive care, management and treatment site), an

South Africa

A two sample test of proportions, crude and adjusted relative



Maotoe T, et al, 2013

immediately after testing HIV-positive improved retention in care

the pilot period)

NGO supported site located in a public teaching hospital in Johannesburg

risks were estimated using poison approach

Muchedzi A, Chadambuka A, Chikwinya B, Mahomva A, 2012

Assessing whether introducing PoC CD4 machines increasing the proportion of HIV pregnant women assessed for ART eligibility and subsequently initiated ART

A quasi experimental before and after study design

2310 HIV positive pregnant women(1210 in the baseline and 1100 in the pilot)

Prospective (before and after deployment of PoC CD4 machines

43 high volume PMTCT sites

Zimbabwe

Wilcoxon signed rank test was used to test difference between proportions

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