Epidemiology, drug resistance and pathogenesis of HIV in Cape Verde: the Cape Verde HIV Cohort

HIV-1 affects a significant number of individuals in Cape Verde and even though antiretroviral treatment is available for all patients in need, drug resistance has increased to alarming rates in recent years. Resistance testing is required to help select effective second-line ART regimens and prevent further transmission of drug resistant isolates. Virtually nothing is
known about the acute phase of HIV-2 infection and how it sets the stage for the attenuated course of infection that is typical of this virus. HIV-2 represented 12% of new infections in 2015
in Cape Verde making this country an ideal place to study the acute phase of HIV-2 infection.
The overall objectives of this project are to obtain a detailed understanding of the HIV epidemiology, drug resistance and pathogenesis in Cape Verde. Specific objectives are: 1) to
determine the rates of primary and secondary drug resistance in HIV-1 and HIV-2-infected patients; 2) to characterize the neutralizing antibody response in HIV-2-infected patients during
acute infection and its impact in virus evolution and disease progression; and 3) to study the contribution of host restriction factors SAMHD1 and tetherin in the control of HIV-2 replication
and disease progression. In task 1 the HIV Cape Verde Cohort will be established. This will be a prospective cohort of 225 HIV-1-infected (110 drug-naïve and 115 failing ART therapy) and 75
HIV-2-infected individuals enrolled and followed at the Hospitals and Health Centers in São Vicente and Praia over a three-year period. Socio-demographic, clinical and laboratory data will
be collected at study entry and every 6 months thereafter. Blood samples will be collected at each visit for analysis in subsequent tasks. In task 2 we will obtain updated data on the epidemiology of HIV-1 and HIV-2 drug resistance. This will require sequencing the pol gene of treated and untreated patients, identifying drug resistance mutations and tracing back the origin of resistant isolates by phylogeographic analysis. In task 3 Env-pseudotyped viruses and a single-cycle infectivity assay will be used to determine the potency and breadth of antibody neutralization in sequential samples obtained from patients with recent HIV-2 infection. The impact of antibody neutralization in viral evolution, pathogenesis and disease progression will be investigated. In task 4, we will determine the relative prevalence of SAMHD1 splice variants in HIV-2-infected individuals and investigate the possible correlation with disease progression.
We will also investigate the role of Vpx variants from HIV-2-infected individuals in the antagonism of SAMHD1 activity. Finally, we will assess the ability of primary HIV-2 Env proteins to neutralize tetherin. This will require cloning env genes from HIV-2 patients in 6-month intervals to observe longitudinal changes in the envelope sequences, to study their associated Vpu-like properties and establish possible correlations with disease progression.