Challenge for optimal care for people living with HIV in countries with limited resources: findings from observational studies from different settings.

To date, more than 78 million people have been infected with HIV and an estimated 42 million people have died of an AIDS-related illness. The epidemic remains a major threat, with 35 million people currently living with HIV-infection and 2.1 million newly infected annually. Corresponding with efforts to expand access to antiretroviral treatment (ART), there has been an increasing emphasis on attaining the high levels of retention and adherence necessary to achieve good clinical outcomes. Retention is a critical determinant of adherence as patients must actively attend and participate in an ART care programme to receive their medication and to have their HIV clinical indicators monitored. Incomplete adherence and early treatment discontinuation remain among the strongest predictors of incomplete viral suppression, disease progression, and mortality among individuals living with HIV. The HIV epidemic also led to a major increase in tuberculosis (TB) cases and tuberculosis mortality, especially in southern and eastern Africa. Among people living with HIV, TB is the most frequent life-threatening opportunistic infection and a leading cause of death. HIVpositive TB patients experience higher mortality rates than HIV-negative TB patients, especially those with smear-negative pulmonary or extrapulmonary tuberculosis. Delayed TB diagnosis may be an important contributor to this excess mortality in HIV-infected persons. This work is based on data from observational studies in 6 countries: Cambodia, the Democratic Republic of Congo, Uganda, Tanzania, Zambia and Malawi. This work aims to provide evidence about barriers along the continuum of care for people living with HIV and to suggest possible solutions. It also provides evidence about the challenges in the diagnosis of tuberculosis among people living with HIV, and the impact of the WHO 2007 guideline on the diagnosis of TB in people living with HIV. The specific objectives of this thesis are: 1. To estimate retention levels of patients on ART and identify individual risk factors and programme characteristics associated with better levels of retention. 2. To characterize patient ART adherence levels across multiple programme settings and to examine the relationship between individual and programme level characteristics and incomplete adherence. 3. To identify the most common reasons for missing an antiretroviral (ARV) drug dose and to investigate the role of symptoms in missing ARV drugs. 4. To evaluate the WHO 2007 guidelines to improve the diagnosis of TB in HIVpositive patients in terms of operational performance of the guideline, the incremental yield of examinations, the diagnostic accuracy for smear-negative TB and impact on TB diagnosis. The first objective was to estimate the level of retention among different ART programmes and to assess individual and programme level factors associated with better levels of retention. Two cohort studies were used for this: one in the Democratic Republic of Congo and one multi-country study on retention in Tanzania, Uganda and Zambia. Retention during the period of decentralization in an entire district in rural Malawi was also examined, and the drivers for the change in retention over this period were explored. Data from these studies demonstrated that earlier ART initiation and decentralization of services are likely to yield the greatest public health impact in national ART programmes. But to achieve the ambitious goal of universal coverage in rural Africa, treatment will need to expand further to serve communities beyond the reach of current clinics. The potential of decentralization of ART delivery (through mobile clinics and community pharmacies) and community participation (through community health workers and the patients and their families) need to be explored further. However, targeted interventions are needed for certain sub-groups (male persons, young persons and pregnant women). The second objective was to estimate the level of adherence among different ART programmes, and to assess individual and programme level factors associated with incomplete adherence. The most common reasons for missing an antiretroviral (ARV) drug dose were identified and the role of symptoms in incomplete adherence was also assessed. Data from a cross-sectional multi-country study on adherence in Tanzania, Uganda and Zambia indicated that social and behavioural factors have a major importance on impacting adherence. Interventions are needed to address alcohol abuse and internalized stigma, also for patients who have been on ART for longer periods. These interventions should be integrated in ART programmes. Further research is needed into poverty alleviation strategies (like livelihood programmes and cash transfer interventions) and its impact on stigma. Interventions enhancing social support may improve adherence, community programmes (community ART groups or ART clubs for example) should be considered for broader implementation. The role of traditional healers and alternative medicines in lives of adults living with HIV in sub-Saharan Africa emphasizes the need to engage traditional healers and alternative medicines in HIV care. The third objective was to identify the most common reasons for missing an antiretroviral (ARV) drug dose and to investigate the role of symptoms in incomplete adherence. Real or perceived side effects were a common reason for missing a dose of ARV drugs, together with simply forgetting and having no food. A combination of ART regimens with fewer side effects, use of mobile phone text messaging and integration of food supplementation and livelihood programmes into HIV programmes, has the potential to decrease missed doses of ARV drugs and hence to improve adherence and the outcomes of ART programmes. The fourth objective was to assess the operational performance of the 2007 WHO guideline to improve the diagnosis of tuberculosis in ambulatory HIV-positive adults by conducting a prospective cohort study in Cambodia. The impact of reclassifying people with single (including “scanty”) positive smears as smear-positive pulmonary tuberculosis cases on measured burden and outcomes was assessed during a retrospective study in Malawi. The WHO 2007 guidelines are meant for settings where the HIV prevalence exceeds 1% in the general population or 5% among the TB cases. In the Cambodian study, the HIV prevalence varied greatly across sites, highlighting the need for targeted interventions and to identify within low HIV-prevalent countries the settings where the guideline should be implemented. Whilst awaiting the rollout and implementation of easy point-of-care rapid diagnostic tests for TB disease as the Xpert MTB/RIF assay, diagnostic algorithms have a role to play. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable and reduces delay in treatment if the recommendations are implemented. There is however reluctance to comply with the guideline in terms of immediate treatment initiation. Reclassifying patients with scanty and single positive smears will increase the sensitivity of TB diagnosis, and are likely to reduce treatment delay and mortality among a group of patients who previously had a poor prognosis. The effect on TB notification rates will be substantial.

Keywords:B780-tropical-medicine