Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naïve HIV-1 infected US military personnel.

OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.

Immune activation and virologic response to immunization in recent HIV type 1 seroconverters.

Antigenic stimulation from invasive bacterial infections, and the vaccines designed to prevent them, may promote T cell activation and enhancement of HIV-1 replication. Changes in viral load have been correlated with antigen-specific responses. We prospectively determined the impact of immunization with 23-valent pneumococcal vaccine (PVAX) and Haemophilus influenzae type b (Hib)-modified diphtheria toxoid CRM197 (DT) vaccine on HIV-1 replication in recent HIV-1 seroconverters (n = 14; median, 5.5 months from infection; median CD4+ T cells, 535 microl), and correlated results with vaccine-related immune activation. Specific antibody responses, markers of CD4+ T cell activation (transferrin and interleukin 2 receptors), and viral burden were measured at weeks -2 (pre), 0, 1, 2, 6, and 12 after immunization. By week 2, levels of IgG had increased significantly over baseline in both HIV-1-infected patients and HIV-1-seronegative control subjects (n = 9) for each antigen (geometric mean fold rise: PVAX, 10.1 versus 5.3; Hib, 16.0 versus 11.7; and DT, 26.2 versus 24.5, respectively). Despite these vigorous responses to both polysaccharide and protein antigens, HIV-1-infected patients showed limited evidence of CD4+ T cell activation at 1 week, no consistent rise in HIV-1 burden at any point, and no decline in CD4+ T cell number over time. We conclude that recent HIV-1 seroconverters show vigorous humoral responses to vaccine antigens and limited early evidence of T cell activation, but no substantial or sustained increase in viral replication or decline in CD4+ T cell number. Thus, respiratory bacterial vaccines appear immunogenic and safe early in HIV-1 infection.

The changing economics of HIV care.

New advances in human immunodeficiency virus (HIV) monitoring and therapeutics have led to dramatic changes in the course of HIV disease. We evaluated our closed clinic of 425 HIV patients over the period 1995-1998 to determine the cost effectiveness of these changes in care. We found that the costs of antiretroviral therapy tripled over the period of observation, but that these increases were largely offset by major declines in inpatient and home health expenditures. In addition, we found that annual mortality among our HIV patients had declined by 90%. We calculated that the cost per life-year gained is about $17,500, which compares favorably with medical expenditures for renal dialysis or advanced cardiac disease.

Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although influenza vaccination is recommended in persons infected with HIV-1, its efficacy is unknown. OBJECTIVE: To assess the immunogenicity, efficacy, and risks associated with influenza vaccination in persons infected with HIV-1. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient military clinic. PATIENTS: 102 patients with HIV-1 infection. INTERVENTION: Influenza vaccine (n = 55) or saline placebo (n = 47). MEASUREMENTS: Influenza antibody titers, CD4+ cell counts, and plasma HIV-1 RNA levels at baseline, 1 month after immunization, and 3 months after immunization; viral cultures from persons presenting with respiratory illness; and respiratory symptom interview. RESULTS: Twenty-three placebo recipients (49%) and 16 vaccine recipients (29%) reported respiratory symptoms (P = 0.04). Ten placebo recipients but no vaccine recipients had laboratory-confirmed symptomatic influenza (P < 0.001) (protective efficacy, 100% [95% CI, 73% to 100%]). No effect on plasma HIV-1 RNA levels or CD4+ cell counts was noted. CONCLUSION: Influenza vaccination is highly effective in HIV-1-infected persons and does not seem to be associated with substantial changes in viral load or CD4 cell count.

Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial.

Annual influenza vaccine is recommended for persons with HIV infection. Recent reports indicate that immunizations may increase HIV replication in infected individuals. Forty-seven HIV-infected patients were randomized to influenza vaccine or saline placebo using a double blind study design. One month after vaccination, plasma HIV-1 RNA increased in the vaccinated but not placebo group (p = 0.029). At 3 months, CD4% dropped an average of 1.6 points in the vaccinated group compared to an increase of 0.1 points in the placebo group (p = 0.039). Patients on stable antiretroviral regimens had CD4% drop an average of 2.3 points in the vaccinated group at 3 months versus 0.1 points in the placebo group (p = 0.015). It is concluded that HIV-infected patients are at risk for increased HIV replication and decreases in CD4% following influenza vaccination. Since influenza has not been associated with significant morbidity in this population, further study of routine influenza vaccination for HIV-infected patients is warranted.

Bartonella henselae serostatus is not correlated with neurocognitive decline in HIV infection.

Bartonella henselae has been implicated as a significant cause of HIV-associated dementia. We attempted to confirm this association by utilizing the database of the San Diego HIV Neurobehavioral Research Center, which collects longitudinal neurocognitive and laboratory data on over 500 HIV-infected participants. Utilizing an immunofluorescent assay we found that 11% of 177 subjects, half of whom had documented neurocognitive decline, were seropositive for B. henselae. There was no correlation between B. henselae seropositivity and neurocognitive decline. The role of B. henselae in HIV-associated dementia remains ambiguous.

Drug resistance patterns, genetic subtypes, clinical features, and risk factors in military personnel with HIV-1 seroconversion.

BACKGROUND: Regular testing of military personnel identifies early HIV infection; this identification provides a sentinel cohort in which to describe the evolving molecular epidemiology of HIV-1 transmission. OBJECTIVE: To describe the prevalence and epidemiologic correlates associated with the acquisition of non-subtype B and drug-resistant HIV infections. DESIGN: Cross-sectional study. SETTING: Military referral hospital. PATIENTS: 95 military personnel with HIV-1 seroconversion. MEASUREMENTS: Self-reported questionnaire, CD4 cell counts, plasma HIV-1 RNA levels, and nucleic acid sequence analysis for drug-resistant mutations and HIV-1 genetic subtype. RESULTS: 95 patients were enrolled between February 1997 and February 1998. The likely geographic location of HIV-1 acquisition was overseas in 8% of patients, the United States in 68%, and either overseas or the United States in 24%. Seven patients (7.4%) had subtype E infection; the remainder had subtype B infection. Eight of 31 (26%) treatment-naive patients had mutations in the reverse transcriptase or protease gene associated with drug resistance. CONCLUSIONS: The percentage of HIV-1 non-subtype B infection and antiretroviral drug-resistant mutations was relatively high in U.S. military personnel with recently acquired HIV-1 infection.