The Role of ARV Associated Adverse Drug Reactions in Influencing Adherence Among HIV-Infected

The role of ARV associated adverse drug reactions in influencing adherence among HIV-infected individuals: A systematic review and qualitative meta-synthesis. Supplementary Data

Table I: Supplementary table showing search terms used in article search on “The role of adverse ARV reactions in influencing adherence among HIV-infected individuals: A qualitative meta-synthesis adherence”

PubMed search / Web of Science search / All the other databases
Adherence / (Adherence[tw] OR adhere[tiab] OR nonadherence[tiab] OR compliance[tw] OR comply[tiab] OR noncompliance[tiab] OR Retain[tiab] OR retention[tw] OR retained[tiab] OR Uptake[tiab]) / TS=(Adherence OR compliance OR retention OR adhere OR nonadherence OR comply OR noncompliance OR Retain OR retained OR Uptake) / (Adherence OR compliance OR retention OR adhere OR nonadherence OR comply OR noncompliance OR Retain OR retained OR Uptake)
ARV / AND
(ARV[tiab] OR ARVs[tiab] OR ART[tiab] OR HAART[tiab] OR antiretroviral[tiab] OR antiretrovirals[tiab] OR “anti-retroviral"[tw] OR “anti-retrovirals”[tiab] OR stavudine[tw] OR D4T[tiab] OR zidovudine[tw] OR AZT[tiab] OR azidothymidine[tw]) / AND
TS=(ARV OR ARVs OR ART OR HAART OR antiretroviral OR antiretrovirals OR “anti-retroviral" OR “anti-retrovirals” OR stavudine OR D4T OR zidovudine OR AZT OR azidothymidine) / AND
(ARV OR ARVs OR ART OR HAART OR antiretroviral OR antiretrovirals OR anti-retroviral OR anti-retrovirals OR stavudine OR D4T OR zidovudine OR AZT OR azidothymidine)
HIV/AIDS / AND
((HIV[tw] OR “human immunodeficiency virus”[tiab] OR AIDS[tw] OR “acquired immunodeficiency syndrome”[tw] OR serostatus[tw] OR PLHIV[tiab] OR PLWHA[tiab]) OR ((viral OR virally OR HIV) AND (suppress OR suppression OR suppressed))) / AND
TS= ((HIV OR “human immunodeficiency virus” OR AIDS OR “acquired immunodeficiency syndrome” OR serostatus OR PLHIV OR PLWHA) OR ((viral OR virally OR HIV) AND (suppress OR suppression OR suppressed))) / AND
((HIV OR “human immunodeficiency virus” OR AIDS OR “acquired immunodeficiency syndrome” OR serostatus OR PLHIV OR PLWHA) OR ((viral OR virally OR HIV) AND (suppress OR suppression OR suppressed)))
Adverse drug reactions / AND
( ( (side OR adverse OR unintended OR unintentional OR unwanted OR unexpected OR undesirable) AND (reaction OR reactions OR effect OR effects OR event OR events)) OR side effects[tw] OR adverse effects[tw] OR toxic[tiab] OR toxicity[tiab] OR toxicities[tiab] OR “drug safety”[tiab] OR “drug surveillance”[tiab] OR harm[tiab] OR harms[tiab] OR harmful[tiab] OR “product surveillance”[tiab] OR complication[tiab] OR complications[tiab] OR safety[tiab] OR safe[tiab] OR lipodystrophy[tw] OR lipodystrophies[tiab] OR lipohypertrophy[tiab] OR lipohypertrophies[tiab] OR lipoatrophy[tiab] OR lipoatrophies[tiab] OR “buffalo hump”[tiab] OR “Peripheral neuropathy”[tiab] OR nausea[tw] OR nauseated[tiab] OR nauseous[tiab] OR headache[tw] OR headaches[tiab]) / AND
TS= ( ( (side OR adverse OR unintended OR unintentional OR unwanted OR unexpected OR undesirable) AND (reaction OR reactions OR effect OR effects OR event OR events)) OR side effects OR adverse effects OR toxic OR toxicity OR toxicities OR “drug safety” OR “drug surveillance” OR harm OR harms OR harmful OR “product surveillance” OR complication OR complications OR safety OR safe OR lipodystrophy OR lipodystrophies OR lipohypertrophy OR lipohypertrophies OR lipoatrophy OR lipoatrophies OR “buffalo hump” OR “Peripheral neuropathy” OR nausea OR nauseated OR nauseous OR headache OR headaches) / AND
( ( (side OR adverse OR unintended OR unintentional OR unwanted OR unexpected OR undesirable) AND (reaction OR reactions OR effect OR effects OR event OR events)) OR toxic OR toxicity OR toxicities OR “drug safety” OR “drug surveillance” OR harm OR harms OR harmful OR “product surveillance” OR complication OR complications OR safety OR safe OR lipodystrophy OR lipodystrophies OR lipohypertrophy OR lipohypertrophies OR lipoatrophy OR lipoatrophies OR “buffalo hump” OR “Peripheral neuropathy” OR nausea OR nauseated OR nauseous OR headache OR headaches)
Qualitative studies / AND (((“semi-structured”[TIAB] OR semistructured[TIAB] OR unstructured[TIAB] OR informal[TIAB] OR “in-depth”[TIAB] OR indepth[TIAB] OR “face-to-face”[TIAB] OR structured[TIAB] OR guide[TIAB] OR guides[TIAB]) AND (interview[TIAB] OR interviews[tiab] OR interviewed[tiab] OR discussion[TIAB] OR discussions[tiab] OR questionnaire[TIAB] OR questionnaires[tw]))
OR ((transcript OR transcripts) AND (analysis OR analyses OR analyze OR analyzed))
OR “focus group”[TIAB] OR “focus groups”[TW] OR qualitative[TIAB] OR ethnography[TIAB] OR ethnographies[tiab] OR ethnographic[tiab] OR fieldwork[TIAB] OR “field work”[TIAB] OR “key informant”[TIAB] OR participant observation[tiab] OR participant observations[tiab] OR anthropology[tw] OR anthropological[tiab] OR anthropologic OR narrative[tiab] OR narratives[tiab] OR voice[tiab] OR story telling[tiab] OR storytelling[tiab] OR stories[tiab] OR case study[tw] OR descriptive study[tiab] OR descriptive studies[tiab] OR relational approach[tiab] OR naturalistic generalization[tiab] OR phenomenological[tiab] OR phenomenology[tiab] OR stakeholder[tiab] OR stakeholders[tiab] OR “content thematic approach”[tiab] OR formative[tiab] OR grounded theory[tw] OR narration[tw] OR “interviews as topic”[Mesh] OR qualitative research[Mesh] OR "personal narratives as topic"[Mesh] OR “anecdotes as topic”[Mesh]) / AND TS= (((“semi-structured” OR semistructured OR unstructured OR informal OR “in-depth” OR indepth OR “face-to-face” OR structured OR guide OR guides) AND (interview OR interviews OR interviewed OR discussion OR discussions OR questionnaire OR questionnaires))
OR ((transcript OR transcripts) AND (analysis OR analyses OR analyze OR analyzed))
OR “focus group” OR “focus groups” OR qualitative OR ethnography OR ethnographies OR ethnographic OR fieldwork OR “field work” OR “key informant” OR participant observation OR participant observations OR anthropology OR anthropological OR anthropologic OR narrative OR narratives OR narration OR voice OR story telling OR storytelling OR stories OR case study OR descriptive study OR descriptive studies OR relational approach OR naturalistic generalization OR phenomenological OR phenomenology OR stakeholder OR stakeholders OR “content thematic approach” OR formative OR grounded theory OR interview OR interviews OR anecdote OR anecdotes) / AND
(((“semi-structured” OR semistructured OR unstructured OR informal OR “in-depth” OR indepth OR “face-to-face” OR structured OR guide OR guides) AND (interview OR interviews OR interviewed OR discussion OR discussions OR questionnaire OR questionnaires))
OR ((transcript OR transcripts) AND (analysis OR analyses OR analyze OR analyzed))
OR “focus group” OR “focus groups” OR qualitative OR ethnography OR ethnographies OR ethnographic OR fieldwork OR “field work” OR “key informant” OR participant observation OR participant observations OR anthropology OR anthropological OR anthropologic OR narrative OR narratives OR voice OR story telling OR storytelling OR stories OR case study OR descriptive study OR descriptive studies OR relational approach OR naturalistic generalization OR phenomenological OR phenomenology OR stakeholder OR stakeholders OR “content thematic approach” OR formative OR grounded theory OR narration OR interview OR interviews OR anecdote OR anecdotes)

Table II: supplement table showing detailed outline of CERQual confidence assessment for each review emerging theme observed.

Review Finding / Relevant Papers / Methodological Limitations / Coherence / Relevance / Adequacy / Confidence / Explanation of confidence in the evidence assessment
Emotional and psychological problems associated with ARV adverse reactions were occasionally severe enough to cause non-adherence. / 17, 19, 20, 37, 40, 47, 49 / Generally minor concerns. Sample sizes in some study were small and hence additional research will be required to enable generalization of findings. Women were also under represented in one study and this may have influenced the final conclusion that women were more likely to be prescribed or accept HAART. Other studies may not have outlined all emerging themes from the focus group discussions hence it is possible unique themes would be developed with future discussions. 6 minor concerns; 1 moderate concern / Overall high coherence across all studies. Data findings and conclusions were similar in across studies / Overall high relevance 4 high relevance; 2 partial relevance; 1 uncertain relevance / 7 studies 4countries [1 HIC, 1 MIC, 2 LIC] 4 USA; 2 Asia;1 East Africa Rich data / High / 7 studies with minor methodological limitations. Adequately data from 4 countries predominantly high and middle income countries. High coherence
Visually noticeable adverse drug reactions led to HIV disclosure, self-stigma, and decreased adherence. / .
15,19,21,23, 25, 28, 29, 32, 35, 38, 39, 40, 42, 45, 49, 50 / Reasonably acceptable concerns. Some of the limitations included small sample sizes making it impossible to generalize findings to the entire population, Great congruency was observed between patients and care providers in one study to the extent that, information reached saturation as fast as the 12th interview. The study was also made up of mostly male participants and hence cannot be generalized to represent the whole clinic HIV positive population. 2 major concerns; 3 moderate concerns; 11 minor concerns / Sufficiently high coherence. Similar findings across all contributing studies / Overall high relevance 8 high relevance; 5 partial relevance; 1 uncertain relevance / 16 studies 10countries [5 HIC, 3 MIC, 5 LIC] 4 USA; 7 East Africa; 2 Europe; 2 Asia; 1 South Africa Sufficiently rich data / High / 16 studies with minor to significant methodological limitations. Rich data from 10 countries across wide geographical regions predominantly Eastern Africa. High coherence
HIV-infected individuals on EFV-containing regiments reported that EFV-associated adverse drug reactions contributed to poor adherence. / 47,48,49,50,51,52 / Study findings cannot be generalized for some studies since the study site was limited to the Southern part of the country. Also, some studies only focused on findings derived from participants’ response to interview questions but without observing clients reactions. Another study excluded bedridden patients and patients who were unable to attend the clinic due to one reason or another during the study period. Finally, authors of one article raised concerns over participants possibly mistaking disease progress symptoms for ARV side effects.Overall minor to moderate concerns. 2 moderate concerns; 4 minor concerns / Sufficiently high coherence / Overall moderate relevance. 2 high relevance; 3 partial relevance; 1 uncertain relevance / 6 studies total 6 countries [1 HIC, 1 MIC, 4 LIC] 4 East Africa; 1 Asia; 1 USA. Rich data / Moderate / 6 studies with minor to moderate methodological limitations. Sufficient data from 6 countries predominantly low income countries. Fairly high coherence
When HIV-infected individuals had prior knowledge of ARV-related adverse effects, or had been informed in advance of potential ARV-related adverse reactions and how to better manage them, they hence felt these adverse drug reactions were expected, normal and manageable, and therefore reported less non-adherence. / 35, 38, 48, 50 / In one study, participants were all active support group members and hence influenced findings since they were more likely to be adherent than less-involved people. Also, some moderators for some of the focus group discussions were known by the participants and this may have hindered some speaking openly about their non-adherence.
Overall reasonably acceptable limitations. 1 major concern; 3 minor concerns / High coherence of findings / Overall moderate relevance. 2 high relevance; 2 partial relevance / 4 studies total 4 countries [4 LIC] 4 East Africa Fairly rich data / Moderate / 4 studies with minor to significant methodological limitations. Moderately thick data from 4 countries predominantly East Africa. High coherence
The experience of adverse drug reactions resulted in children’s refusal to take ARVs. It’s even very hard for guardians to force their sick children to take ARVs, and they sometimes let their children’s dose slide. / 24, 45, 46 / The small sample sizes of the studies make hinders generalization of study findings. In addition, the presence of caregivers/guardians may have hindered some children from freely airing out their emotions. Whiles, the approach to strangers may have also intimidated some children from speaking up about side effects and non-adherence.
Generally minor methodological concerns. 2 minor; 1 moderate / Moderate coherence due to limited data / Overall moderate relevance. 1 high relevance; 2 partial relevance / 3 Studies 3 countries [1 HIC, 1 MIC, 1 LIC] 1 USA; 1 South America;1 East Africa Low data richness / Moderate / 3 studies with minor to moderate methodological limitations. Fairly sufficient data from 3 countries across a wide geographic region. Moderate coherence
When HIV-infected individuals practiced strategized coping mechanisms to manage adverse drug reactions, they persistently adhere to ARV. / 31, 38, 45 / In one study, the contradicting benefits of ARVs to other treatments such as traditional medicine have been over been biased since the interviewers were professionals mainly trained in Western medicine. Also, participants were only from one hospital known for its quality in HIV services delivery and this may have influenced patients’ perception and opinions about the use of traditional medicine. In addition, the authors analysis of patients’ attitudes by dichotomizing them as positive or negative may not be a true representation of the complicated and dynamic relationship between the use of ARVs and traditional medicine for HIV treatment.
Reasonably acceptable concerns. 3 moderate concerns / Generally acceptable level of coherence. Similar findings across two papers with 1 uncertain due to limited data / Overall moderate relevance. 2 high relevance; 1 uncertain relevance / 3 Studies 4 countries [1 MIC, 3 LIC] 1 Asia; 3 East Africa Low data richness / Moderate / 3 studies with moderate methodological limitations. Fairly sufficient data from 4 countries predominantly low income countries. Moderate coherence
When patients experienced the effectiveness of ARV maintaining their health, side effect was associated with persistent adherence. / 30, 31, 45, 48 / Sample sizes were small and hence cannot be generalized. Also, the actual magnitude of the issues mentioned in some of the studies is unknown.
Generally minor to moderate methodological concerns. 3 moderate concerns / Good coherence of findings / Overall moderate relevance. 1 high relevance; 3 partial relevance / 4 Studies 3 countries [2 MIC, 1 LIC] 1South America, 1East Africa; 1Asia Fairly rich data / Moderate / 4 studies with moderate methodological limitations. Thick data from 4 countries predominantly East Africa. High coherence
Pregnant women/women with history of childbirth distrusted powerful medication and worried ARV’s potential adverse effects on their unborn babies, which was perceived as so toxic and the risk associated with treatment was perceived as greater than the likelihood of their unborn baby being HIV positive. The adverse drug effects of ARVs worsen the reaction of pregnancy, which made these women felt that ARVs did more harm than good. / 16, 36 / The sample sizes were small and hence cannot be generalized.
Overall minor concerns. 2 minor concerns / Uncertain level of coherence due to limited data. However, similar findings across both studies. / Overall moderate relevance. 2 high relevance / 2 Studies 2countries [2 HIC] 1 USA; 1 Australia Limited data / Low / 2 studies with minor methodological limitations. Insufficient data from 2 high income countries. Coherence couldn’t be properly accessed due to limited data.