Pre-treatment drug resistance and HIV-1 subtypes in infants from Argentina with and without exposure to antiretroviral drugs for prevention of mother-to-child transmission.

OBJECTIVES: To assess the prevalence and patterns of pre-treatment HIV drug resistance (PDR) and HIV-1 subtype in infants from Argentina with exposure to different antiretroviral drugs (ARVs) for the prevention of mother-to-child transmission (PMTCT). PATIENTS AND METHODS: HIV-1 genotyping was performed in 115 infants (median age = 2.3 months) born between 2007 and 2014 to screen for drug resistance mutations (DRMs) before starting first-line ART. HIV-1 subtype was characterized by phylogenetic and recombination analysis. RESULTS: Overall, DRMs were found in 34 of 115 infants (PDR level 30% to any ARV, 3.5% to PIs, 12% to NRTIs and 22% to NNRTIs). Of the 115 infants, 22 (19.1%) were ARV-unexposed. Another 93 were ARV-exposed: 28 (24.3%) to short-course zidovudine monotherapy ARV prophylaxis; 25 (21.7%) to nevirapine-based ARV prophylaxis; 12 (10.4%) to perinatal infant zidovudine prophylaxis + maternal combination ART with NNRTIs; and 28 (24.3%) to perinatal infant zidovudine prophylaxis+maternal combination ART with PIs. Transmitted drug resistance among ARV-unexposed infants was 32% (5% to PIs, 9% to NRTIs and 18% to NNRTIs). ART-exposed infants showed multi-class ARV resistance. Importantly, vertical transmission of a triple-class-resistant virus was confirmed in one case. Patterns of DRMs predicted high-level resistance to NNRTIs in a similar and high proportion (>50%) of infants with at least one DRM independently of ARV exposure. BF recombinants were found in 74%, subtype B in 20%, subtype C in 3% and novel AG and AB recombinants in 3%. CONCLUSIONS: PDR in HIV-1-infected children from Argentina is among the highest reported, jeopardizing successful lifelong suppressive ART as well as the efficacy of current PMTCT regimens.

Kinetics of HIV-1 in cerebrospinal fluid and plasma in cryptococcal meningitis.

In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF) and plasma in patients with cryptococcal meningitis (CM), we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy-free HIV-infected patients with CM. Samples were obtained at baseline (S1) and at the second (S2) and third (S3) weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died) showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease.

Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis.

BACKGROUND: The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF HIV-1 viral load and HIV-1 plasma viral load; and (3) CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. METHODS: Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006). We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche). Data were processed with Statistix 7.0 software (linear regression analysis). RESULTS: Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01). No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123). CONCLUSION: Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.