Optimizing HIV care in West Africa

Datum: 21 januari 2014

Locatie: UAntwerp - Campus Drie Eiken - Promotiezaal - Universiteitsplein 1 - 2610 Wilrijk

Tijdstip: 18 uur

Organisatie / co-organisatie: Faculty of Medicine and Health Sciences

Promovendus: Kevin Peterson

Promotor: Prof. B. Colebunders

Korte beschrijving: PhD defence Kevin Peterson - Faculty of Medicine and Health Sciences



Abstract

This thesis focuses on opportunities to improve HIV care in West Africa. Although the roll-out of antiretroviral therapy (ART) in sub-Saharan Africa has been highly successful HIV care remains sub-optimal and tools for its betterment are either now, or will soon be, available.  Key constraints specific to West Africa that need to be addressed are the presence of HIV-2 and the limited resources available for care. Most of the research presented in this thesis took place at the Medical Research Council’s (MRC’s) Gambia Unit, specifically the Genito-Urinary Medicine (GUM) Clinic where from October 2004 to June 2010 ART was available as part of a national program supported by the Global Fund for AIDS, TB, and Malaria (GF-ATM). 

Main results

HIV-2 ART recommendations
Antiretroviral combinations consisting of three nucleoside analogs, and those using unboosted protease inhibitors, previously common in the treatment of HIV-2 in low-income settings, performed poorly.  We demonstrated that virologic suppression on a par with that achieved in HIV-1 was possible using ritonavir-boosted lopinavir in first line ART for individuals with HIV-2 infection.  There is a clear need for effective ARVs from “new” classes for the treatment of HIV-2.  When the integrase inhibitor raltegravir, first licensed for use in HIV-1 infection, was used in HIV-2 this yielded mixed, largely negative results despite in vitro evidence of efficacy.  A case series presented in this thesis demonstrates that if it is used in conjunction with an optimized background regimen of sufficient potency, raltegravir can generate a durable viral suppression despite its low threshold for developing resistance. Whether its proper place in the current armamentarium is in first- or second-line therapy remains an open question.

Literacy, education, and adherence
We found lower levels of formal education and literacy to be associated with treatment failure mediated through poorer ART adherence.  This suggests that literacy and/or education should be assessed prior to ART initiation; identifying those at risk for poor adherence allows them to be targeted for greater adherence support.

Predicting viremia with self-reported adherence and keeping to appointments
Suboptimal antiretroviral adherence typically precedes HIV viremia and subsequent immunologic decline.  We demonstrated that self-reported adherence was modestly effective at predicting viremia.  Missed appointments were shown to predict viremia across a wide range of days by which they were missed, while not adding predictive power to self-reported adherence in multiple regression analysis.  This suggests that in our setting missing appointments is a characteristic of non-adherent patients, not the cause of their missed doses.

Depression screening
In a first study we screened 44 individuals not yet on ART using the CES-D10 score for depression and the IES-R score for post-traumatic stress disorder (PTSD).  With over 40% of the subjects testing positive for either condition, this study suggests a serious burden of disease.  Depression was associated with low CD4 counts and not having an independent income.  The well-established relationship between depression and poor ART adherence argues for incorporating depression screening into the process of preparing individuals for ART.  In a second study we performed depression and PTSD screening among 252 people on ART.  This study revealed a strikingly lower prevalence of depression compared to the study of people not yet on ART.  This is in contrast to the results of PTSD screening.  We interpret this as a response to ART through reduction in symptoms and short-term risks of illness and death.  It is however also possible that the lower prevalence of depression was the result of higher mortality among depressed patients rather than recovery from their depression. 

Conclusions
Confirming and staging an individual’s HIV infection in a timely manner, including early CD4 testing, is the first step towards improving care.  Screening for illness and risk factors for a poor treatment response is a key element of pre-ART care, and can be roughly grouped into three categories.  The first is screening for the classic OIs such as tuberculosis and cryptococcal meningitis, which are a substantial source of morbidity and mortality both directly and through IRIS.  The second category of screening includes those conditions that negatively affect ART adherence such as financial and social barriers to treatment, illiteracy, substance abuse, and depression.  The third category of screening focuses on those conditions that promote HIV transmission.  

A general lesson I draw from my research and experiences during my tenure at the GUM clinic is the value of investing in high quality patient care.  Reliable diagnostics, effective counseling, and good care and follow-up are expensive and time consuming.  I assert however that the short-term costs are largely outweighed by the long term benefits.