In sub-Saharan Africa, the introduction of antiretroviral therapy (ART) for patients with HIV has improved the lives of millions and decreased mortality. However, the means of monitoring the effects and side effects of ART are frequently not available and African HIV clinics still face numerous obstacles in delivering ART at a sufficiently high quality thus placing patients’ lives in jeopardy. Furthermore, guidelines for treatment of HIV in Africa are copies of the guidelines used in Europe and North America.
The overall aim of this thesis was to describe and analyze the challenges related to ART delivery in Guinea-Bissau, and to conduct a randomized controlled HIV treatment trial in this setting. This PhD thesis consists of two original research papers and two manuscripts. The specific aims were:
• To give a presentation of the Bissau HIV cohort.
• To determine if CD4 cell count measurement is useful for detecting treatment failure in HIV-1 infected patients in Bissau.
• To evaluate levels of HIV-1 resistance among patients with HIV-1 and HIV-1/2 dual infections treated with ART.
• To evaluate two different antiretroviral regimens in HIV-1 infected patients in the randomized controlled PIONA trial:
A) An NNRTI (efavirenz/nevirapine) based regimen and
B) A PI (ritonavir-boosted lopinavir) based regimen
with regard to effect on HIV RNA evaluated as the fraction of patients having below 400 copies/ml after treatment for 12 months.
The main findings of this thesis were:
• From July 2007 until June 2013, 3,762 patients were included in the Bissau HIV Cohort. The cohort is the world’s largest single-center cohort of HIV-2 infected patients. Thus, this cohort represents a unique opportunity to study how co-infections alter immune response, disease progression and response to treatment.
• One-third of all patients at the HIV clinic in Bissau were not assessed for treatment failure; one-third of those who were assessed experienced treatment failure; and two-thirds of patients experiencing treatment failure were not switched to second-line treatments. Consequently, patients who experienced treatment failure had increased mortality.
• A large proportion of HIV-1 and HIV-1/2 dual infections developed virological failure (46%) after a median follow-up of six months. Furthermore, over half of these patients developed resistance - predominantly to NNRTIs.
• A PI-based treatment regimen was not superior to an NNRTI-based treatment regimen after 12 months of follow-up regarding virological suppression, CD4 cell count increase, or mortality among HIV-1 infected patients in the randomized controlled PIONA trial. Both regimens were equally well tolerated apart from a higher frequency of grade 1 and grade 2 laboratory abnormalities in the NNRTI arm. Patients receiving PIs had a lower adherence than patients receiving NNRTIs.
Longer follow-up of patients in the PIONA trial and resistance testing will reveal overall efficacy of NNRTIs compared to PIs. NNRTI resistance is common among patients in the Bissau HIV Cohort and since the HIV-1 epidemic in Guinea-Bissau is still young, the problem is only expected to increase during the coming years. During the course of this PhD project, it became clear that the HIV clinic in Bissau still faces numerous obstacles in delivering ART at a sufficiently high quality. Promoting adherence and decreasing loss to follow-up must be a top priority in Bissau. Future research by the Bissau HIV cohort study group will demonstrate whether our identification of problems with the delivery of ART has led to measurable benefits.