Title: Incidence of loss to follow-up and associated factors among mothers on antiretroviral
therapy in the context of elimination of mother-to-child transmission of HIV in two health
districts of Bobo-Dioulasso in Burkina Faso
Version: 4 Date: 30 Aug 2024
Reviewer's report:
This article analyses factors associated with loss to follow-up among women living with HIV
diagnosed during pregnancy as part of a PMTCT program in two districts of Burkina Faso.
The current version of the paper presents different weaknesses, and several revisions are required
before publication.
My first concern is a lack of information regarding the length of observations among women
selected for the analysis. It is said that these women were diagnosed and initiated ART between
2017 and 2020, and that the analysis was run between May 2023 and March 2024. However,
on what date was data extracted from the database? May 2023? How long are women supposed
to be followed in this database? 24 months after childbirth? Longer? Are they supposed to be
followed for HIV in the same centre? Or are they supposed to be transferred to another HIV
care centre after a certain period of time?
Did the analysis include all observation time, or was it censored right after a certain period
(e.g., 24 months after childbirth)? Because it will change the research question. A statement
like “Regular long-term monitoring of maternal ART is an important part of HIV management
and therefore of protecting children, through improved compliance with treatment.” in the
introduction is ambiguous. In terms of preventing a child from HIV acquisition, antiretroviral
treatment of the mother is important during pregnancy, birth, and breastfeeding. However, after
that, antiretroviral treatment of the mother does not affect HIV transmission. It is crucial for the
individual health of the mother. You could argue that having a healthy mother will also benefit
the child in general. However, it is not related anymore to the prevention of HIV transmission.
If the focus is loss of follow-up specifically in the context of PMTCT, then it would be relevant
to add a proper right census to the data, and analyse only loss to follow-up during that specific
period. Otherwise, the introduction and discussion should be rewritten to consider both mid-
term and long-term issues related to loss to follow-up.
In all cases, it would be relevant to provide proper information on the duration time of each
participant, for example with a figure showing the distribution in supplements.
BACKGROUND
More contextual information would be welcomed. In particular, how is organised HIV care of
women after pregnancy? Also could the authors provide information about breastfeeding in the
context (frequency? Duration?)?
“No published study  has been carried out to explore the relationship between LTFU and
persistence of new paediatric HIV in  Burkina Faso.” Not related to the purpose of this paper as
the presented analysis does not explore this relationship.
METHODS
The paper's title mentioned Bobo-Dioulasso, while the methods mentioned Do and Dafra health
districts. It seems inconsistent. Provide more context regarding these two districts.
“They were not declared transferred  or deceased,”. Why excluding women transferred or
deceased? They should be included in the analysis with a right census at the date of transfer
or death.
Why not include the district as one of the explanatory factors? According to Figure 1, LTFU is
very different in the two districts.
“Number of children”: it is unclear. Do you include the child who was just born? Twins are
couted as two?
Overall, there is a methodological problem. The outcome is not being loss-to-followup but
the time when a woman becomes lost to follow-up. Considering the proportion being LTFU
is improper as observation time differs per woman. Therefore, a Chi² test cannot be used for
comparing groups. Proper bivariate comparisons could be done by (1) comparing incidence rate
(i.e. number of LTFU divided by person time); (2) Kaplan-Meier curves and test; (3) univariable
Cox model.
“multivariate Cox model”: it would be more accurate to say “multivariable Cox model”.
“The Schoenfeld test was used to assess the validity of the model.” More precisely, this test
verifies that the model's proportional hazards assumption is valid.
RESULTS
Study participants: this not the place to present estimates of LTFU. That section should only
discuss the selection of study participants.
Section “Socio-demographic characteristics of study participants”: this section should only
present the characteristics of the study population. The presentation of estimates of LTFU should
arrive later, and then bivariate associations.
Table 1: the proportion of LTFU is not an appropriate indicator and chi² test is therefore not
relevant here. It would be more appropriate to provide numbers of LTFU, person_years and then
incidence rate.
Why rural and urban are presented in talic?
Some variables are still presented in French and have not been translated to English.
“Incidence of loss to follow-up” To hel the reader to visualizean incidence of 1.91 per 100
person-months, it would be helpful to also translate it in an annual incidence (i.e. 22.9%).
“On average, patients had a follow-up time of eighteen months before being  lost to follow-up
(mean = 17.52 months).” Once again, this is not a proper indicator as all women have not been
exposed the same amount of time.
Propers indicators could be derived from the Kaplan-Meier curve, e.g. the time when 20% of
participants were LTFU.
This overall Kaplan-Meier curve, with proper confidence intervals and a risk table would be
appropriate. See for example https://www.danieldsjoberg.com/ggsurvfit/
Fig 2 and Fig 3 should also be updated with confidence intervals, risk tables and p-value.
Why does the figure stop at Month 24? Right census of the data or just a zoom on the plot?
DISCUSSION
“The average length of follow-up  before LTFU was around 18 months.” Improper indicator,
see previous comment.
“The high incidence of LTFU shows that women are adhering to the strategy.” ???? This is the
opposite.
“The new WHO  recommendations propose starting treatment for any patient screened, even
in the absence of a  paraclinical work-up; this should support a low incidence rate.”  Add a
reference to these recommendations. Which year? Before or after the data collection?
“The high incidence  of LTFU will contribute to an increase in the rate of HIV MTCT, which is
9.3% according to routine data  from the Hauts Bassin region [22].” No. If incidence is stable,
transmission should be stable. A change in LTFU incidence could have an impact on the change
in terms of transmission. It should be reformulated.
“Studies have shown that pregnancy has a  positive influence on mothers' adherence to treatment;
they seek to protect their child [24–26].” I do not see the point here.
“The  average follow-up time shows a slackening towards the end of the eMTCT. It is easy
for women to attend  health facilities when their children are being monitored as part of the
extended preventive immunization  programme. The programme ends when the child reaches
18 months.” If the end of the program impacts LTFU, you should see a drop on the Kaplan-
Meier curve. But according to figures 2 and 3, LTFU is quite uniform over time and it does
seem that there is a threshold effect.
“This could be explained  by a lack of maturity and a carefree attitude to life. The youngest people
are not yet aware of their  responsibilities and their role as mothers.” This is over-interpreting
the results and could be perceived as a moral judgment.
“Fear of stigmatisation can lead to LTFU” Reference required
“Our results are similar  to those of Mushy and colleagues in Tanzania [29].” Which are?
“More than a third of women missed their supply appointment over a period of three  successive
months.” Cf. previous comments.
“Studies have  shown that patients who started treatment on the same day when they were
screened were less compliant  than than those initiating later ... [35–37].” How is it related to
the results of the paper?
“The incidence of LTFU in this study was higher than the 9.4 per 1000 person-months of Azanaw
et al.  [38] and the 12.04 per 1000 person-months of Geremew et al [34].” Please provide context
about these two studies (conducted in Ethiopia). Why is it comparable?
“The shorter duration of follow-up for some women in the two studies could  explain the lower
incidence of loss to follow-up.” Only if incidence during the first months is different to incidence
after M3.
“It has limitations linked to the absence of certain information on clinical and  sociodemographic
data.” Which variables in particular would habe been relevant and not available in the data?
“We only collected data from women newly screened during the eMTCT pregnancy.” Replace
“screened” by “diagnosed”.
“However, our results do not preclude decisions to  improve follow-up in general, and especially
for mothers in rural areas.” I do not understand that point. To be reformulated?
“It shows an association between the place of  residence, age and the LTFU status.” To be
reformulated. It is not an association with a “LTFU status” but with the timing of LTFU. Cox
models correspond to a longitudinal perspective, not a cross-sectional one.