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1.
J Acquir Immune Defic Syndr ; 89(2): 183-190, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34629415

RESUMO

INTRODUCTION: Early systemic and central nervous system viral replication and inflammation may affect brain integrity in people with HIV, leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART. METHODS: HIV-infected MSM and transgender women (average age: 27 years and education: 13 years) enrolled within 100 days from the estimated date of detectable infection (EDDI). A cognitive performance (NP) protocol was administered at enrollment (before ART initiation) and every 24 weeks until week 192. An overall index of cognitive performance (NPZ) was created using local normative data. Blood (n = 87) and cerebrospinal fluid (CSF; n = 29) biomarkers of inflammation and neuronal injury were examined before ART initiation. Regression analyses assessed relationships between time since EDDI, pre-ART biomarkers, and NPZ. RESULTS: Adjusting for multiple comparisons, shorter time since EDDI was associated with higher pre-ART VL and multiple biomarkers in plasma and CSF. NPZ scores were within the normative range at baseline (NPZ = 0.52) and at each follow-up visit, with a modest increase through week 192. Plasma or CSF biomarkers were not correlated with NP scores at baseline or after ART. CONCLUSIONS: Biomarkers of CNS inflammation, immune activation, and neuronal injury peak early and then decline during acute HIV infection, confirming and extending results of other studies. Neither plasma nor CSF biomarkers during acute infection corresponded to NP scores before or after sustained ART in this cohort with few psychosocial risk factors for cognitive impairment.


Assuntos
Infecções por HIV , Adulto , Biomarcadores , Cognição , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inflamação/complicações
2.
J Int AIDS Soc ; 22(11): e25411, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31773888

RESUMO

INTRODUCTION: Transmitted, or any pretreatment drug resistance (TDR, PDR) can compromise efficacy of first-line antiretroviral therapy (ART). In Peru, genotypic resistance testing is not routinely performed before ART initiation, and estimated PDR prevalence prior to 2012 ranged from 1.0% to 4.7%. We aimed to update estimates of PDR prevalence in men who have sex with men (cis-MSM) and transgender women (TW). METHODS: We obtained HIV sequences from three studies of ART-naïve cisgender-MSM and TW (n = 470) in Lima, Peru from 2013 to 2017, almost two-thirds of whom had acute or recent infections. Sanger sequences of HIV pol were interrogated for surveillance drug resistance mutations (SDRM) using the Stanford Calibrated Population Resistance (CPR) tool and scored for resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) with the HIVdb programme. We calculated binomial proportions and 95% confidence intervals. χ2 and exact or trend tests were used to examine predictors of PDR. RESULTS: Seventy-seven (16.4%) individuals had PDR (95% CI: 13.2 to 20.0); most resistance was likely TDR since 63% were incident infections. SDRM were present in 9.8% (7.3 to 12.9). Resistance to any NRTI was present in <1% of individuals, while efavirenz resistance was present in 10% (6.9% to 12.4%). TW were not statistically more likely than cis-MSM to have PDR (11.4% vs. 9.1%, p = 0.54). Age, incident versus prevalent infection, or residence district did not predict PDR. Prevalence of SDRM increased from 3% in 2013 to 21% 2017 within incident infections (p = 0.04), but not when including prevalent infections. CONCLUSIONS: Prevalence of NNRTI resistance in three studies of ART-naïve MSM and TW in Lima, Peru reaches 10%. Because our study reports PDR in a population in which most acquired HIV recently, the overall prevalence of PDR, including previously treated persons, is likely underestimated. These results underscore the need for a nationally representative survey of PDR in Peru and consideration of non-NNRTI anchored first-line ART options. This study also represents the first evaluation of PDR in cis-MSM versus TW in South America, and demonstrates that, although TW are at higher risk of acquiring HIV, they are at similar risk of acquiring a virus with resistance mutations.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Homossexualidade Masculina , Pessoas Transgênero , Adulto , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Peru/epidemiologia , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto Jovem
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