In this cohort of women starting ART in Johannesburg and who received extensive adherence support, we explored the association between socio-economic characteristics, adherence and virologic failure during the first 24 weeks of treatment. There was a high level of adherence despite the social and economic challenges faced by these participants, many of whom were single mothers living in disadvantaged economic circumstances. These observations are consistent with other studies from SSA [28–31] and reflect patients' commitment to HIV care in South Africa.
Reduced adherence, measured as a percent of doses missed in a given time period, has been associated with virologic failure. The relationship between adherence and virologic failure appears to be affected by the classes of drugs used and may differ between early and later treatment[32, 33]. In our data, it appeared that previous use of sdNVP may affect the relationship between adherence and virologic failure of an NNRTI-containing regimen. In the total study population, less than 80% adherence was significantly associated with virologic failure. However, when women were stratified by exposure to sdNVP, the effect of adherence on virologic failure was strongest among the sdNVP exposed women, where anything less than 95% adherence was significantly associated with increased virologic failure. This might be due to the selection and persistence of NVP resistance mutations, albeit as minority species undetected in consensus sequence. In addition, the higher the level of adherence to NNRTI-based therapy, the lower the risk of drug resistance and virologic failure[18, 32]. This contrasts with the unexposed women among whom there was no association between reduced levels of adherence and virologic failure. This difference may be a result of the relatively small number of unexposed women (n = 57) and should be confirmed in larger prospective studies. Nevertheless, our findings raise the question of whether drug resistance selected by sdNVP may be partially overcome with complete adherence.
The primary study was designed to assess the effect of sdNVP on virologic response to therapy. Although exposure to sdNVP in the prior 18-36 months was not associated with a reduced likelihood of achieving and sustaining viral suppression, women with minority K103N mutations before treatment had a reduced durability of virologic suppression as observed in other studies[20, 22, 35, 36]. Some studies, however, have reported poor virologic response to NNRTI-based therapy even if exposure is quite distant. These differences between studies may, in part be explained by different levels of adherence. If the effects of incomplete adherence on virologic suppression depend on past drug exposure, as suggested by our data, studies with less attention to sustaining high levels of adherence may detect decreased efficacy of ART among those with past exposure to sdNVP. Since current guidelines recommend that pregnant women with <350 CD4+ cells/mm3 receive ART, rather than sdNVP, there is less basis to be concerned about the impact of sdNVP on later treatment outcomes. Adherence level to ART is found to be high among HIV infected pregnant women compared to non-pregnant women[40, 41]. However, ART is a life-time treatment and sustaining high adherence level should remain the ultimate goal.
The women who had participated in the pMTCT program were more likely to be adherent to ART in univariable analysis although this association did not remain after adjustment for social characteristics. Increased treatment preparation in pMTCT programs may provide women with information about ART and adherence as shown in a study in Uganda. Another study at a rural district hospital in South Africa demonstrated that women provided with partner support and complete pMTCT information were more likely to take sdNVP. Thus, programs that provide sdNVP for pMTCT and provide women with increased treatment education, information and support are likely to achieve better adherence on ART. Here, women, with less education were at higher risk for incomplete adherence. Other studies of women and of men and women found independent associations between education, health literacy and adherence to ART. An additional concern is women's understanding of their children's treatment needs, where poor education may pose an additional risk for inadequate administration of ART to their infected children.
In Johannesburg, less education, living in an informal setting and providing care for at least two children with uncertain partner support, were each associated with reduced adherence and an increased need for support. Ware and co-workers found, in a large ethnographic study in Nigeria, Tanzania and Uganda, that social support enhances adherence. Also Merenstein and co-workers found that having the sole responsibility for a child reduces adherence among women in the United States. Lack of potable water at home as reported by Ellis and co-workers in Nairobi was associated with incomplete adherence among both adults and children. In this study, we observed that patients with low socio-economic status, assessed by living in an informal dwelling, the absence of a TV or lack of potable water at home were each associated with incomplete adherence although these did not retain significance in the final model, possibly because of the small sample size. The three main reasons for missing pills were being away from home, being busy with other things and simply forgetting, which are consistent with the findings of a review by Mills and co-workers.
There are several limitations to the generalizability of this study. Postpartum women are a vulnerable population who may have particular difficulty in obtaining access to ART due to financial challenges as described by Rosen and co-workers. Here we followed a relatively small number of women for only six months and did not monitor changes in socioeconomic status, relationships, employment or depression over time. Rather, we relied on baseline responses and recall at six months. Reimbursement for transport costs, estimated to be ~25% of the patients' cost of ART, may have improved adherence to treatment. In addition, this was a clinical research study in which attention and resources were devoted to reinforcing adherence, so it is likely that incomplete adherence may be more prevalent in a routine HIV care setting. Further limitations include focus only on a single measure of adherence and uncertain validity of some of the co-factors investigated, including QOL. Adherence to ART is a dynamic process influenced by psychosocial and socio-economic factors that need further investigation.