|The present thesis describes the implementation of the HIV Programme in Guinea-Bissau and the process of setting up the WARAID cohort study. This cohort consists in a clinical database and biobank of HIV-infected individuals followed in the Anti Retroviral Treatment (ART) Centre localized at the National Simão Mendes Hospital (NSMH-ART) in Bissau.
The work has resulted in three manuscripts which forms the basis of this thesis.
The first paper describes the evolution seen in the number and characteristics of patients followed in the NSMH-ART Centre since the introduction of ART in the country in 2005. In a four-year period, the number of new patients being enrolled went from 23 in 2005 to 964 in 2009. Although HIV-1 infected subjects represented the majority of patients included in the clinic, single and double HIV-2 infections still accounted for one third of the subjects enrolled. High rates of early mortality were observed during the first 4 months after enrolment in HIV care, even when ART was initiated immediately. This poor survival was probably associated with late access to ART and advanced symptomatic disease at presentation. This paper also shows how rapid and unplanned increases in the number of patients receiving ART between 2007 and 2009 have provoked serious shortages of ARV drugs during this period and the potential consequences of this situation. The scarcity of antiretroviral (ARV) drugs turned in unnecessary changes in ART regimens and even in the interruption of the therapy to some patients. Furthermore, it is emphasised that there is a need for indicators that can evaluate the quality of the ART provided by the national HIV programme in the worldwide monitoring of the effect of general introduction of ART.
The second paper presents a practical example of the dangerous adverse reactions that the abrupt disruption of ARV drugs may trigger in patients on ART and how changes in regimens are driven by the availability rather than by clinical criteria in a context of limited accessibility of ARV drugs. Stevens-Johnson syndrome (SJS) is a rare but potentially severe cutaneous adverse reaction. The normal frequency of SJS described in HIV patients on ART is relative low, less than 2%. However, in October 2008, after a shortage of Efavirez and the consequent change of ART regimens containing this drug to Nevirapine, three cases of SJS were described in HIV-1 infected patients followed in the NSMH-ART clinic in an unusual short time frame of 5 weeks.
Finally the third paper describes risk factors for early mortality within 6 months among HV patients included in the WARAID cohort study. Associations between baseline anthropometric measurements, CD4 cell count, plasma suPAR levels (the soluble form of the urokinase plasminogen activator receptor) and survival during the first 6 months of follow-up were examined using Cox proportional hazards models. Irrespective of ART initiation and baseline CD4 count, mid-upper-arm-circumference (MUAC) and the soluble form of the urokinase plasminogen activator receptor (suPAR) plasma levels were independent predictors of mortality in HIV patients enrolled in this urban cohort. These findings suggest that these markers could be used to identify patients at highest risk of short-term mortality and to assess ART eligibility when CD4 cell count is not available. Identification of simple tools for identifying patients at highest risk of death is necessary for rural areas with poor access to laboratory facilities. Furthermore, this paper also explores potential ways to select patients to whom ART must be prioritized in situations with limited stock of ARV drugs. This is relevant for countries such as Guinea-Bissau where most patients are enrolled at an advanced clinical stage and the unstable drug supply prevent ART initiation to all patients that fulfil eligibility criteria for ART according to the CD4 count.