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Baseline characteristics of study sites and women enrolled in a three-arm cluster randomized controlled trial: PMTCT uptake and retention (pure) Malawi

  • Monique van Lettow1, 2Email author,
  • Hannock Tweya3, 4,
  • Nora E. Rosenberg5, 6,
  • Clement Trapence3,
  • Virginia Kayoyo5,
  • Florence Kasende1,
  • Blessings Kaunda7,
  • Mina C. Hosseinipour5, 8,
  • Michael Eliya9,
  • Fabian Cataldo1,
  • Salem Gugsa3,
  • Sam Phiri3, 8, 10 and
  • for the PURE Malawi consortium
Reproductive Health201714:82

DOI: 10.1186/s12978-017-0343-0

Received: 4 May 2017

Accepted: 30 June 2017

Published: 11 July 2017

Abstract

Background

Malawi introduced an ambitious public health program known as “Option B+” which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of WHO clinical stage or CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating the effect of peer-support on care-seeking and retention in care.

Methods/design

PURE Malawi was a three-arm cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. 21 sites (clusters) were selected for inclusion in the study. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial.

Results

Study implementation was managed by 3 partner organizations; each responsible for 7 study sites. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Study sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Enrollment occurred from November 2013 to November 2014, over a median period of 31 weeks (range 17–51) by site. A total of 1269 HIV-infected pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART under Option B+, were enrolled. Each site reached or surpassed the minimum sample size. Comparing the number of women enrolled versus antenatal cohort reports, sites recruited a median of 90% (IQR 75–100) of eligible reported women. In the majority of sites the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of reported pregnant and lactating women starting ART in the same sites. The median age of all women was 27 (IQR 22–31) years. All women have ≥20 months of possible follow-up time; 96% ≥ 2 years (24–32 months).

Conclusion

The PURE Malawi study showed that 3 implementing partner organizations could successfully recruit a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline.

Trial registration

This study is registered at clinicaltrials.gov - ID Number NCT02005835. Registered 4 December, 2013.

Keywords

PMTCT Uptake Retention Peer-support Cluster randomized trial Malawi Feasibility

Plain english summary

Malawi introduced a new strategy that aims at preventing HIV infection from mother to child. There is no cure for HIV, but medication (antiretroviral treatment) is available to slow the progression of the virus and help prevent transmission of HIV to others. The so called “Option B+” strategy means that all HIV-infected pregnant and breastfeeding women start antiretroviral treatment as soon as they are diagnosed. The PMTCT Uptake and REtention (PURE) study evaluated whether support provided by peers (mothers who are HIV-infected and on treatment themselves) can help to increase the number of HIV-infected pregnant and breastfeeding women to start treatment (uptake) and keep them in care and on treatment (retention). The study took place in 21 health facilities, where mothers either received no peer support (7 sites), peer support in the facility (7 sites) or peer support in the community (7 sites). This article describes how the study was successfully set up and managed by 3 organizations. Between November 2013 and November 2014, a total of 1269 HIV-infected women were included in the study in the 21 health facilities. We describe that it is possible to set up a complex study across 3 geographical zones in Malawi.

Background

In 2011, Malawi introduced an ambitious public health strategy known as “Option B+”, providing a standardized lifelong combination antiretroviral therapy (ART) regimen to all HIV-infected pregnant and breastfeeding women, irrespective of their CD4 cell count or World Health Organisation (WHO) clinical stage of HIV infection. This public health approach for the prevention of mother to child transmission (PMTCT) of HIV has since been adopted by several other countries in the region and was included in the updated WHO guidelines in 2013 [1]. Initial data have demonstrated that the Option B+ strategy has resulted in large increases in the number of pregnant women accessing PMTCT [2]. However, concerns have been raised about the level of attrition of women from care [3]. Although the strategy offers an attractive rapid ART scale-up and has the potential to profoundly impact maternal and infant outcomes, services supporting the implementation of Option B + have not been formally evaluated. Several issues were identified at the national level as potential threats to the successful implementation and scale up of the strategy: a) potential suboptimal uptake of ART by asymptomatic pregnant women due to low treatment literacy and stigma; b) low adherence to ART and poor follow-up of HIV exposed infants; and c) lack of psycho-social support for long term retention in this relatively asymptomatic patient population [4]. Hence, it seemed apparent that the identification of interventions to support PMTCT uptake and retention would be the first step towards improvement. A recently published systematic review identified 9 completed studies and 5 ongoing trials which examined initiation of ART in pregnant women [5]. While the authors report several promising interventions for improving ART initiation, the quality of evidence was insufficient to support recommendations. In addition, results for ART initiation in pregnant women were not independently examined, and maternal retention in PMTCT care and exposed infants care were not assessed.

Although randomized controlled trials are promoted as the highest level of evidence for the evaluation of interventions, the implementation of rigorous trials within the context of the public health sector are complex and therefore still uncommon [6]. PURE Malawi embraced the challenge of implementing a multi-site controlled trial within the context of public health clinics under real world conditions in Malawi. PURE Malawi was a three-arm cluster randomized controlled trial that aimed at evaluating whether facility- or community-based peer-support would enhance care-seeking and retention in care by HIV-infected pregnant and breastfeeding women, their HIV-exposed infants, and their male sex partners, and ultimately improve health outcomes in all three populations. The hypothesis was that enhanced support for women and their families within facilities and/or community would result in improved retention in the continuum of PMTCT care. The primary trial outcome is the proportion of women retained in care, 2 years after they initiated antiretroviral therapy under the Option B+ strategy. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial.

Methods

PURE Malawi was a three-arm stratified cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+. The three arms differed with respect to the presence and location of one-on-one patient education and support, support groups, visit reminders, and missed visit follow-up. The trial was unblinded to study participants and health care providers, but blinded to outcome assessors. A comprehensive description of the study arms was reported elsewhere [7]. The PURE trial was managed by the PURE Malawi consortium comprising of governmental, non-governmental, research, and academic partners. The consortium was led by Lighthouse Trust. Dignitas International, The University of Malawi College of Medicine Malaria Alert Centre, and University of North Carolina Project were each responsible for trial implementation in one Malawian zone. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Selection and responsibilities of all consortium members were described elsewhere [7].

Site selection and recruitment targets

Clusters (i.e. health facilities) were the unit of randomization in this trial. Public health facilities in the South East, South West, and Central West health zones of Malawi, covering the central and southern geographical regions of Malawi, were assessed for eligibility in the trial. Sites were eligible if they provided Option B+ services, did not have additional PMTCT interventions or research activities beyond the Malawi national standard of care, and were expected to have at least 20 eligible women for Option B+ in a 6 month period. HIV care in Malawi is free and standardized in all public health facilities. Site assessments, selection and randomization of the sites were described elsewhere [7].

Twenty-one selected sites were stratified into 3 groups of 7, with each group having sites of comparable size and expected retention, based on Ministry of Health historic data. Depending on the size of the health facility, each site was expected to reach a minimum enrollment target of 20, 50, 75, or 125 pregnant or breastfeeding women eligible for the Option B+ program. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. Sites could exceed this target if they finished enrollment prior to a 6 month period.

Enrolment process and index participants

Prior to study implementation, all Ministry of Health staff working at ANC and ART departments in the selected sites received training in study arm specific standard operating procedures, adherence to ethical standards and management of data collection tools (Good Clinical Practice). At each site, a PURE site coordinator was selected to oversee the study implementation.

All newly identified HIV positive women identified during pregnancy, delivery, or breastfeeding while seeking antenatal care (ANC) or initiating ART services at the study sites were eligible for inclusion in the study. Women consented to participate and be followed in the site where they had sought ANC or ART services and were explained in which arm the site was allocated.

Based on existing PMTCT monitoring data, we anticipated 6 months until sample size was achieved.

All participating women were assigned a unique study ID. Study ID stickers were placed in the study register, the mother’s existing health passport and on all routine clinic records for data extraction and tracking.

The index participants were newly confirmed HIV-infected pregnant and breastfeeding women; eligible to initiate ART under Option B+, in the 21 selected health facilities. To attain the primary trial outcome, enrolled women were expected to be followed until the end of the study period (31st July 2016), transfer out, default, or death.

Data collection and management during recruitment period

All newly identified HIV positive women were eligible for inclusion in the study. Therefore, routinely collected health facility cohort data prepared during quarterly supervision visits [8] was used to compare the number of women enrolled in the study with the number of eligible women seeking care at the health facility during the recruitment period. Monthly ANC cohort data included the number of women newly registered, newly diagnosed with HIV or already known HIV-infected, and those already on ART. ART cohort data included the number of pregnant and lactating women having started ART per quarter.

Facility characteristics data, including availability of HIV Testing Services (HTS), ANC and ART services were collected by existing study personnel throughout the enrolment period.

During study enrollment, health facility staff used PURE registration and PURE enrolment forms to collect data on mothers’ age, expected delivery date (pregnant women) or date of birth of the child (lactating women), marital status, and whether the partner lives in the catchment area.

At the ART initiation visit, a routinely used clinical card was initiated and treatment initiation data were recorded, including date, age and reason for initiation of ART (WHO stage or pregnant/lactating), TB and KS. The data collection and analytic methods, including a detailed analysis plan, for the final trial outcomes were described elsewhere [7].

Compensation of health facility for study specific activities

During the enrolment period, each health facility received 1000 MK (equivalent to approximately 2 USD) per correctly enrolled study participant, in addition to a median amount of 5000 MK per month (equivalent to approximately 10 USD) for correct organization and storage of clinical and study records as stipulated by the national guidelines and PURE protocols. This amount was shared among the facility staff involved in the study.

Results

PURE Malawi sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Table 1 shows PURE Malawi sites by health zone, implementing partner and study arm. Each implementing partner managed the implementation of the study across the 7 sites in the respective health zone where the partners operate. The organization Mothers2Mothers provided additional support for training and implementation in all Arm 2 sites. Table 2 shows the number of Ministry of Health staff trained by site and cadre prior to study implementation. Enrollment initiation varied per trial site from November 2013 through January 2014. Recruitment was completed in November 2014. Median enrollment time per site was 31 weeks, ranging from 17 to 51 weeks. Table 3 describes the number of pregnant and lactating women enrolled per site and arm, in addition to the number of eligible women reported in cohort reports at ANC and ART during the recruitment period. Each site and arm reached or surpassed the minimum sample. However, a few participants (4%) were enrolled later than the desired end date of July 31st 2014, making 2 years of follow up impossible by July 31, 2016, the trial end date.
Table 1

PURE Malawi sites by health zone, implementing partner and study arm

Implementing partner

Central west zone

South east zone

South west zone

University of North Carolina Project, Lilongwe

Dignitas International, Zomba

Malaria Alert Centre, Blantyre

Arm 1

Daeyang Luke Hospital Publicc

Mulanje District Hospitala

Mwanza District Hospitala

Kasinje Health Centred

Mimosa Dispensarye

Chirimba Health Centred

Dr David Livingstone Memorial Clinicf

  

Arm 2

Lobi Rural Hospitalc

Muloza Health Centred

Makhetha Health Centred

Mbiza Health Centred

Masenjere Health Centred

 

Mdeka Health Centred

 

Kadidi Health Centerd

Arm 3

Biriwiri Health Centred

Mulanje Mission Hospitalb

Trinity Mission Hospitalb

Nsipe Health Centred

Mulomba Health Centred

 

Bilira Health Centerd

Mpala Health Centred

 

aDistrict Hospital

bMission Hospital

cRural Hospital

dHealth Centre

eDispensary

fPrivate clinic

Table 2

Number of facility staff trained in study procedures and good clinical practices

Arm and facility name

ART/PMTC coordinators

ART/PMTCT providers

HTC providers

ART clerks

Total

Arm 1: Standard

 Mulanje District Hospital

3

7

3

2

15

 Daeyang Luke Hospital Public

2

7

3

1

13

 Mwanza District Hospital

 

1

 

2

3

 Mimosa Dispensary

 

2

2

2

6

 Kasinje Health Centre

 

4

2

2

8

 Dr. David Livingstone Memorial Clinic

 

6

 

1

7

 Chirimba Health Centre

2

6

 

2

8

Arm 2: Facility Support

 Muloza Health Centre

 

3

4

2

9

 Makhetha Health Centre

1

13

1

 

15

 Mbiza Health Centre

1

4

2

2

9

 Masenjere Health Centre

  

2

4

6

 Mdeka Health Centre

4

6

2

2

14

 Lobi Rural Hospital

 

3

2

 

5

 Kadidi Health Centre

 

7

  

7

Arm 3: Community Support

 Mulanje Mission Hospital

1

8

3

2

14

 Trinity Mission Hospital

  

5

10

15

 Mulomba Health Centre

 

2

4

1

7

 Mpala health Centre

1

3

2

2

8

 Biriwiri Health Centre

 

3

3

2

8

 Nsipe Health Centre

 

4

2

1

7

 Bilira Health Center

 

3

2

2

7

Table 3

PURE study enrollment per site and arm versus eligible women reported in cohort data from the same facilities

PURE recruitement

MoH program report cohort data

Arm and facility name

Target per site

Total enrolled

Enrollment period

Pregnant women enrolled

Lactating women enrolled

MoH program report period ANC DATA (monthly)

New ANC registrations

HIV positives womena (not on ART) in ANC

MoH program report period ART DATA (quarterly)

Pregnant women started ART

Lactating women started ART

Arm 1: Standard

 Mulanje District Hospital

125

127

23Jan’14-29Aug’14

122

5

01Jan’14-01Sep’14

1631

149

01Jan’14-30Sep’14

191

34

 Daeyang Luke Hospital Public

75

75

24Dec’13-04Sep’14

65

11

01Dec’13-01Oct’14

1298

71

01Oct’13-30Sep’14

111

18

 Mwanza District Hospital

50

74

09Jan’14-25aug’14

67

8

01Jan’14-01Sep’14

2248

54

01Jan’14-30Sep’14

107

26

 Mimosa Dispensary

50

52

09Jan’14-10Jul’14

37

15

01Jan’14-01Aug’14

557

61

01Jan’14-30Sep’14

53

28

 Kasinje Health Centre

20

49

16Dec’13-08Aug’14

44

5

01Dec’13-1Sep’14

1398

42

01Jan’14-30Sep’14

55

11

 Dr. David Livingstone Memorial Clinic

20

20

19Nov’13-17Nov’14

19

1

01Nov’13-01Dec’14

262

21

01Oct’13-31Dec’14

29

1

 Chirimba Health Centre

20

50

08Jan’14-17Jul’14

48

2

01Jan’14-01Aug’14

724

66

01Jan’14-30Sep’14

71

18

Total

360

447

 

402

47

 

8118

464

 

617

136

Arm 2: Facility Support

 Muloza Health Centre

125

125

27Nov’13-04Jun’14

108

17

01Nov’13-01Jul‘14

1325

161

01Oct’13-30Jun’14

178

34

 Makhetha Health Centre

75

78

13Jan’14-20Aug’14

62

16

01Jan’14-01 Sep’14

711

31

01Jan’14-30 Sep’14

109

39

 Mbiza health Centre

50

52

17Dec’13-08Jul’14

48

4

01Dec’13-01Aug’14

598

51

01Oct’13-30Sep’14

112

12

 Masenjere Health Centre

50

51

11Dec’13-23Jun’14

43

7

01Dec’13-01Jul’14

754

42

01Oct’13-30Jun’14

67

10

 Mdeka Health centre

20

40

06Jan’14-26Jun’14

34

7

01Jan’14-01Jul’14

695

32

01Jan’14-30June’14

46

11

 Lobi Rural Hospital

20

40

22Nov’13-31Jul’14

26

14

01Nov’13-01Aug’14

1472

33

01Oct’13-30Sep’14

39

18

 Kadidi Health Center

20

42

07Jan‘14-06May’14

40

2

01Jan’14-01Jun’14

527

53

01Jan’14-30June’14

66

2

Total

360

428

 

361

67

 

6082

403

 

617

126

Arm 3: Community Support

 Mulanje Mission Hospital

125

125

16Jan’14-13Oct’14

109

16

01J an’ 14-01Nov’14

1912

265

01Jan’14-31Dec’14

255

41

 Trinity Mission Hospital

75

77

04Dec’13-03Oct’14

68

9

01Dec’13-01Nov’14

1529

76

01Oct’13-31Dec’14

119

41

 Mulomba Health Centre

50

52

04De c’13-25Jun’ 14

44

8

01Dec’13-01Jul’14

716

23

01Oct’13-30Jun’14

61

20

 Mpala health Centre

50

52

18Dec’13-11Jul’14

44

8

01Dec’13-01Aug’14

1650

111

01Oct’13-30Sep’14

165

48

 Biriwiri Health Centre

20

26

19Nov’13-24Jul’14

16

10

01Nov’13-01Aug’14

568

21

01Oct’13-30Sep’14

37

20

 Nsipe Health Centre

20

31

07Jan’14-28Jul’14

26

5

01Jan’14-01Aug’14

503

29

01Jan’14-30Sep’14

24

9

 Bilira Health Center

20

31

02Dec’13-31Jul’14

26

5

01Dec’13-01Aug’14

751

22

01Oct’13-30Sep’14

39

13

Total

360

394

 

333

61

 

7629

547

 

700

192

TOTAL

 

1080

1269

 

1096

175

 

21,829

1414

 

1934

454

aPrevious positives (not yet on ART) + new positives

A total of 1269 women were enrolled, 1094 (86%) pregnant and 175 (14%) lactating women.

When comparing number of enrolled pregnant women per site with facility cohort data; 7 sites recruited >100% of the total reported cohort of HIV-infected pregnant women at ANC in the corresponding months. The additional number of pregnant women may have started ART, but not attended ANC in the specific study site. Nine sites recruited >90%, 10 sites 60–90%, and 2 sites 40%–59% of the total reported cohort of pregnant women at ANC in the corresponding months. When comparing the number of women enrolled versus ANC reports, sites recruited a median of 90% (IQR 75–100) of eligible reported women from ANC.

Following quarterly ART cohort report data; in all study sites, a total of 1934 (81%) pregnant and 454 (19%) lactating women had started ART during corresponding quarters. This proportion of pregnant and lactating women was comparable to our study sample.

Baseline characteristics of study sites

Table 4 shows the characteristic of study sites, with regards to services available during the enrolment period. During the enrolment period, 9 facilities experienced a median of 2 weeks of HIV test kit stock outs (range 2–8) and 13 facilities were not able to provide HTC for a median of 4 weeks (range 1–8) due to stock outs or unavailability of HTC providers. The 6 largest facilities provided ANC and ART services during all week days; in all other facilities ANC and ART services were provided at a median of 3 days (range 2–4) and 1 day (range 1–4) per week, respectively. In 19 of the 21 facilities, ART provision was available at ANC.
Table 4

Facility characteristics during enrollment period

Arm and facility name

Enrolment duration in weeks

HIV test kit stockout in weeks

HTC service NOT available in weeks

Number of days per week ANC provided

Number of days per week ART provided

ART provided at ANC (Yes/No)

Arm 1: Standard

 Mulanje District Hospital

31

-

-

5

5

Yes

 Daeyang Luke Hospital Public

36

-

-

4

5

Yes

 Mwanza District Hospital

33

2

2

5

5

Yes

 Mimosa Dispensary

26

-

4

2

1

Yes

 Kasinje Health Centre

33

-

1

5

4

Yes

 Dr. David Livingstone Memorial Clinic

51

-

4

5

5

No

 Chirimba Health Centre

27

-

-

4

1

Yes

Arm 2: Facility Support

 Muloza Health Centre

27

4

4

3

1

Yes

 Makhetha Health Centre

31

8

8

3

1

No

 Mbiza health Centre

29

-

-

2

1

Yes

 Masenjere Health Centre

27

8

8

2

2

Yes

 Mdeka Health centre

24

2

2

2

1

Yes

 Lobi Rural Hospital

36

-

-

5

5

Yes

 Kadidi Health Center

17

2

2

2

1

Yes

Arm 3: Community Support

 Mulanje Mission Hospital

38

-

-

5

5

Yes

 Trinity Mission Hospital

43

4

4

5

5

Yes

 Mulomba Health Centre

29

-

4

2

1

Yes

 Mpala health Centre

29

-

-

3

1

Yes

 Biriwiri Health Centre

35

2

3

3

1

Yes

 Nsipe Health Centre

29

-

-

3

1

Yes

 Bilira Health Center

34

2

2

3

1

Yes

Baseline characteristics of women enrolled in the trial

Cumulative baseline characteristics of women enrolled in the trial are shown in Table 5.
Table 5

Cumulative Baseline characteristics of women included in the study

 

Total

Percent

Pregnant

Percent

Lactating

Percent

P- value (Chi-square)

N

1269

 

1094

86%

175

14%

 

Health Zone

 Central West

272

21%

223

20%

49

28%

0.07

 South East

585

46%

512

47%

73

42%

 

 South West

412

32%

359

33%

53

30%

 

Age

 15–21

266

21%

224

20%

42

24%

0.30

 22–28

488

38%

419

38%

69

39%

 

 29–35

406

32%

355

32%

51

29%

 

  > 36

103

8%

94

9%

9

5%

 

 Missing

6

0.5%

2

0.2%

4

2%

 

Months pre- or postnatal at enrolment

  < 3 months

  

370

34%

42

24%

 

 3–6 months

  

582

53%

22

13%

 

  > 6 months

  

47

4%

51

29%

 

 Missing

  

97

9%

61

35%

 

WHO Stage at ART initiation

 Stage 1 (asymptomatic)

1211

95%

1044

95%

167

95%

0.12

 Stage 2

13

1%

13

1%

   

 Stage 3

10

1%

7

1%

3

2%

 

 Stage 4

-

 

-

 

-

  

 Missing

35

3%

30

3%

5

3%

 

Marital Status

 Never married

21

2%

16

1%

5

3%

0.001

 Maried Monogamous

1068

84%

942

86%

124

71%

 

 Maried Polygamous

110

9%

96

9%

13

7%

 

 Divorced

49

4%

27

2%

22

13%

 

 Widowed

17

1%

7

1%

10

6%

 

 Missing

7

1%

6

1%

1

1%

 

Currently having a sexual partner

 Yes

1193

94%

1053

96%

140

80%

0.001

 No

60

5%

29

3%

31

18%

 

 Missing

16

r

1%

12

r

1%

4

2%

 

Current sexual partner living in catchment area

 Yes

994

83%

878

83%

116

83%

0.43

 No

133

11%

118

11%

14

10%

 

 Missing

66

6%

57

5%

10

7%

 

Enrollment period

 01Oct-31Dec’13

108

9%

94

9%

14

8%

0.67

 01lan-31Mar’14

551

43%

468

43%

83

47%

 

 01Apr-30Jun’14

417

33%

362

33%

55

31%

 

 01lul -30Sep’14

186

15%

163

15%

23

13%

 

 01Oct-31Dec’14

7

1%

7

1%

   

Follow up time from Enrolment to Study End

 20–23 months

47

4%

40

4%

7

4%

0.37

 24–27 months

467

37%

411

38%

56

32%

 

 28–32 months

755

59%

643

59%

112

64%

 

The median age of all women was 27 (IQR 22–31) years, with no difference between those pregnant and lactating. Pregnant women were enrolled at a median of 4 months (IQR 2–5) prenatal; breastfeeding women at a median of 5 months (IQR 1–11) postnatal. Reason for ART initiation for all women was being pregnant or lactating (regardless of CD4 or WHO stage). Among those with WHO stage reported at ART initiation, 98% of both pregnant and lactating women were reported clinically asymptomatic. There was 1 documented TB case (within the last 2 years) and 1 documented KS case at ART initiation.

Proportionally more lactating women reported being divorced, widowed, or having no sexual partner than pregnant women. Among women with at least one sexual partner, 11% were reported not living in the same catchment area as their partner. There was no difference in recruitment by Health Zone period or the time for follow-up between pregnant and lactating women. The largest proportion of women was recruited between January and July 2014, enabling 96% of women to be followed up for at least 2 years (24–32 months) as part of the trial.

Discussion

This paper shows that the PURE consortium was successful in recruiting a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi. Each site and trial arm reached or surpassed the minimum required sample size, and the majority of sites recruited over 90% of the reported eligible women attending ANC during the recruitment period. Although cluster designs are often avoided due to the challenges of enrolling at multiple sites within a reasonable timeline, we show that, despite the absence of remunerated study staff within study site, only few participants were enrolled later than the desired end date; allowing for 96% of the cohort to be followed for at least 2 years. We report that there were HIV test kit stock outs or unavailability of the HTC providers, which may have prolonged the enrolment period. Shortages and stock out of commodities at health facilities is a reality in Malawi, however, national guidelines are set up to improve the supply management [8]. In the majority of participating sites, the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of pregnant and lactating women initiated on ART in the same sites. There was no difference in age between the enrolled pregnant and lactating women. One fifth of the women enrolled were young mothers (15–21), which is consistent with national evaluations that describe women in Malawi’s Option B+ program [3]. Proportionally more lactating women reported being divorced, widowed or having no sexual partner. As male partner support is thought to be an important determinant for uptake and outcomes of PMTCT initiatives [911], follow up of our cohort of mothers with and without partners will add to the evidence on the impact of male partner involvement approaches on PMTCT services. According to Malawi’s demographic health survey, 14% of Malawian women are married to a man with more than one wife. Polygamy is most common in the Northern Region [12], which may explain why we found a lower proportion of women in polygamous marriage (9%). In our study, 98% of pregnant and lactating women were reported clinically asymptomatic. This high proportion of women starting ART in the earliest stages is an indication of the success of Malawi’s PMTCT programming.

Malawi, as the first country to implement Option B+, has the potential to be a leader in developing and documenting highly effective models of service delivery to pregnant and lactating women and enhance retention in lifelong care and treatment. Cluster randomized controlled trials are needed to determine whether promising interventions are indeed effective. However, the implementation of such trials pose a substantial challenge, especially across multiple regions, different facility types, and several implementing partners. Thus, the ability to select 21 comparable clinics, stratify them in a meaningful way, and have each enroll its target sample size is an achievement. This achievement stems from clear leadership, small incentives to clinical staff, and well-coordinated teams.

This paper described the processes for site selection, recruitment, and enrollment of study participants, along with baseline characteristics of study sites and women enrolled in the trial. Follow-up of participants was completed on July 31st, 2016. The final results and outcomes (per protocol) of this study are reported elsewhere [13]. Alongside this trial, a qualitative study has been implemented to explore experiences of patients and health care workers in relation to the implementation of Option B+ and the trial interventions [14].

Limitations

We were not able to report the precise number of women who refused to participate in the study, as this data was not collected consistently across the sites. However, compared to facility cohort data, it appears that we were able to enroll the majority of eligible women.

Conclusions

Malawi, as the first country to implement Option B+, has the potential to be a leader in developing and documenting highly effective models of service delivery to provide needed support to women and enhance retention in lifelong HIV care and treatment approaches. The PURE trial is expected to play a critical role in this process. We show that a consortium of organizations was successful in recruiting a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline.

Declarations

Acknowledgements

We wish to thank the support of all members of the PURE Malawi Consortium.

PURE Malawi Consortium

Sam Phiri, Hannock Tweya, Salem Gugsa, Clement Trapence, Saulos Mhlanga (Lighthouse Trust, Lilongwe, Malawi); Frank Chimbwandira, Michael Eliya (Ministry of Health, Lilongwe, Malawi); Mina Hosseinipour, Nora E. Rosenberg, Innocent Mofolo, Virginia Kayoyo, Christopher Stanley (University of North Carolina Project, Lilongwe, Malawi); Monique van Lettow, Fabian Cataldo, Misheck Nkhata, Florence Kasende, Megan Landes, (Dignitas International, Zomba, Malawi); Don Mathanga, Atupele Kapito-Tembo, Blessings Kaunda-Khangamwa (University of Malawi, College of Medicine, Malaria Alert Centre, Blantyre, Malawi); Levison Chiwaula, Gowokani Chirwa (University of Malawi, Chancellor College, Zomba, Malawi); Erik Schouten (Management Sciences for Health, Lilongwe, Malawi); Veena Sampathkumar (Mothers2Mothers, Lilongwe, Malawi).

Funding

The study was funded by the World Health Organization through an award for the INtegrating and Scaling up PMTCT through Implementation REsearch (INSPIRE) initiative from Global Affairs Canada and AIDS fonds that provided support for virologic and resistance assessment.

Availability of data and materials

The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

Disclaimers (WHO/GAC)

The opinions expressed in this article do not necessarily reflect the views of policies of the World Health Organization, Global Affairs Canada or AIDS fonds.

Authors’ contributions

MvL, HT, NER, MCH, ME, FC and SP contributed to the concept and design of the study. CT, VK, FK, and BK contributed to acquisition of data. MvL, HT and NER contributed to data analysis and/or interpretation of the data. MvL drafted the first manuscript. NER, MVH, FC, SG and SP reviewed and suggested revisions. All authors reviewed and approved the final manuscript.

Ethics approval and consent to participate

Ethical approval was granted through Malawi’s National Health Sciences Research Committee, the University of North Carolina Institutional Review Board, the University of Toronto, and the Ethics Review Committee of the World Health Organization. All women provided written informed consent. There were no protocol amendments.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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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)
Dignitas International
(2)
Dalla Lana School of Public Health, University of Toronto
(3)
Lighthouse Trust
(4)
The International Union against Tuberculosis and Lung Disease
(5)
University of North Carolina Project
(6)
Department of Epidemiology, University of North Carolina
(7)
University of Malawi, College of Medicine, Malaria Alert Centre
(8)
Department of Medicine, University of North Carolina School of Medicine
(9)
Department of HIV and AIDS, Ministry of Health
(10)
Department of Public Health, University of Malawi, College of Medicine, School of Public Health and Family Medicine

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Copyright

© The Author(s). 2017