ABSTRACT
Transmitted resistance to antiretroviral drugs in acute and early HIV-1 infection has been well documented, although overall trends vary depending on geography and cohort characteristics. To describe the changing pattern of transmitted drug-resistant HIV-1 in a well-defined cohort in New York City, a total of 361 patients with acute or recent HIV-1 infection were prospectively studied over a decade (1995-2004) with respect to HIV-1 genotypes and longitudinal T-cell subsets and HIV-1 RNA levels. The prevalence of overall transmitted resistance changed from 13.2% to 24.1% (P = 0.11) during the periods 1995 to 1998 and 2003 to 2004. Nonnucleoside reverse transcriptase inhibitor resistance prevalence increased significantly from 2.6% to 13.4% (P = 0.007) during the same periods, whereas prevalence of multidrug-resistant virus shifted from 2.6% to 9.8% (P = 0.07) but did not achieve statistical significance. A comparable immunologic and virologic response of appropriately treated individuals was observed regardless of viral drug susceptibility status, suggesting that initial combination therapy guided by baseline resistance testing in the case of acute and early infection may result in a favorable treatment response even in the case of a drug-resistant virus. These data have important implications for selection of empiric first-line regimens for treatment of acutely infected antiretroviral-naive individuals and reinforce the need for baseline resistance testing in acute and early HIV-1 infection.
Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral , HIV Infections/transmission , HIV Infections/virology , HIV-1/drug effects , HIV-1/isolation & purification , Adult , Female , Genome, Viral/genetics , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , Humans , Male , Middle Aged , Mutation, Missense , New York City/epidemiology , Phylogeny , Prevalence , RNA, Viral/blood , Sequence Analysis, DNA , T-Lymphocyte Subsets , Treatment Outcome , Viral LoadABSTRACT
BACKGROUND: Rapid progression to AIDS after acute HIV-1 infection, though uncommon, has been noted, as has the transmission of multidrug resistant viruses. Here, we describe a patient in whom these two factors arose concomitantly and assess the effects. METHODS: We did a case study of a patient with HIV-1 seroconversion. We genotyped the virus and host genetic markers by PCR and nucleotide sequencing. To ascertain the drug susceptibility of our patient's HIV-1 we did phenotypic studies with the PhenoSense assay. We assessed viral coreceptor use via syncytium formation in vitro and with a modified PhenoSense assay. FINDINGS: Our patient seems to have been recently infected by a viral variant of HIV-1 resistant to multiple classes of antiretroviral drugs. Furthermore, his virus population is dual tropic for cells that express CCR5 or CXCR4 coreceptor. The infection has resulted in progression to symptomatic AIDS in 4-20 months. INTERPRETATION: The intersection of multidrug resistance and rapid development of AIDS in this patient is of concern, especially in view of his case history, which includes high-risk sexual contacts and use of metamfetamine. The public health ramifications of such a case are great.
