Do patients who are infected with drug-resistant HIV have a different CD4 cell decline after seroconversion? An exploratory analysis in the UK Register of HIV Seroconverters

Abstract

Using data from the UK Register of HIV Sero-converters, we compared the rate of CD4 cell decline in antiretroviral-naive individuals with and without evidence of transmitted drug resistance (TDR). Although there was a suggestion that CD4 cell decline in the first year after seroconversion was faster in those with TDR,there was no evidence of a difference in the rate of decline thereafter. The virological and host determinants of this possible phenomenon are worth further exploration.

Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

“…We quantified the genetic variability with respect to its potential contribution to drug selective pressure using the most recent WHO surveillance drug resistance mutation list [20], a set of known compensatory mutations [21], and an vivo fitness landscape (FL) of drug selective pressure. In this study, viral load and CD4 cell count did not differ between patients with or without TDR, in agreement with earlier reports [23,24]. Evidence of TDR primarily consisted of single mutations, often 215 revertants [4,5], indicating that major resistance mutations had already reverted in the majority of the TDR patients, along with their deleterious effects on virus replication in absence of drug.…”

“…Considering that TDR is largely defined by non-polymorphic treatment-related mutations, mainly reflecting major drug resistance mutations [20], TDR has initially been speculated to result in lower set-point viral loads and higher CD4 cell counts, and consequently a slower disease progression [11]. While studies have reported that transmission of drug-resistant virus was associated with changes in initial viral load and CD4 counts in both seroconverters and chronically HIV-infected patients [11,22], other studies could not corroborate these findings [23,24]. Compensatory mutations often accompany major resistance mutations, selected to restore impaired intrinsic replication capacity [21].…”

Transmitted human immunodeficiency virus-1 drug resistance in a cohort of men who have sex with men in Belo Horizonte, Brazil - 1996-2012

“…A slower rate of CD4 decline has been reported in patients who present TDR mutations (Bhaskaran et al 2004), while others have not found a favourable effect on VL and CD4 counts in the presence of TDR mutations (Chan et al 2003). …”

Early Control of HIV-1 Infection in Long-Term Nonprogressors Followed Since Diagnosis in the ANRS SEROCO/HEMOCO Cohort

“…17,18 A square root transformation was applied to the CD4 cell count to conform model assumption. [19][20][21] The influence of gender 22 and age at inclusion 23 (in 2 categories based on the median) was investigated by adding interaction with the fixed slope and fixed intercept and tested using a likelihood ratio test.…”