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Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 + and CD8 + T cells. Co-culturing CD4 + with autologous CD8 + T cells from ART-suppressed HIV + donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 + T cells. This trispecific antibody mediates CD4 + and CD8 + T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Highly active antiretroviral therapy (HAART) has changed the natural course of HIV infection. However, the toxicities associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs) have led to the assessment of dual-therapy approaches with less toxicity. Atazanavir and dolutegravir have antiviral potency, tolerability and favourable metabolic profile. In suppressed HIV-infected patients, with NRTIs-related toxicity effects, the association of atazanavir and dolutegravir, favoured by their positive pharmacokinetics interaction, could be used as 'maintenance' antiretroviral therapy. We report a case report about one HIV-infected patient, on HAART and with a persistent suppression of HIV RNA, switched to dolutegravir 50 mg three times weekly plus atazanavir 400 mg once daily, as 'maintenance antiretroviral therapy', with persistence of viral suppression.

We describe a case of symptomatic acute HIV infection in a young man where a fourth-generation rapid screening test combining HIV-specific antibody and p24 antigen was negative. In highly suspicious cases of acute HIV infection, plasma HIV RNA assays together with conventional, non-rapid screening tests should be used.

Efavirenz is a non-nucleoside-reverse-transcriptase-inhibitor used as part of highly-active-antiretroviral-therapy for the treatment of the human immunodeficiency virus (HIV) type 1 infection. The present paper aims to describing the impact of efavirenz dose reduction on the pharmaceutical budget at the Verona University Hospital. A budget impact analysis comparing two prescribing scenarios was conducted: all patients treated with the efavirenz full dose (600 mg per day) vs. a proportion of patients treated with a reduced dose (200-400 mg per day). All outpatients referring to the Infectious Disease Clinic in the period November 2009-October 2011 were selected. Out of 132 patients treated with efavirenz, 25 were not considered, mainly due to a too short treatment period. Of the remaining 107 patients, 68 received the full dose, while 39 received a reduced dosage. The analysis included the cost of the drug and of diagnostic tests, from the National Health Service perspective. The daily dose reduction of efavirenz saved 54,664 euros (a 30% expenditure reduction). In sum, new strategies for pharmaceutical system sustainability are necessary; despite forthcoming expiring patents of several drugs, spending on antiretroviral drugs is expected to rise. This paper suggests a way of linking clinical benefits and cost reduction.

To assess the potency, efficacy and toxicity of abacavir/lamivudine (ABC/3TC) versus tenfovir/emcitrabine (TDF/FTC) with efavirenz (EFV) in naive patients with HIV infection a prospective observational study was carried out to evaluate immunovirological parameters every three months and metabolic parameters every six months. In all, 21 patients were enrolled (10 on ABC/3TC and 11 on TDF/FTC). Fisher's test revealed no statistically significant difference between the two arms in terms of immunological recovery and control of viral replication. For metabolic parameters at week 48 no statistically significant differences were noted between the two arms. The two ABC/3TC and TDF/FTC backbones showed the same potency; ABC had a more negative impact on metabolic parameters without statistical power.

We have evaluated CD4+-guided HAART interruption in 46 HIV+ patients with CD4+ > 500/microl and viral load undetectable since at least 3 years. This strategy resulted effective in a long mean period of treatment interruption (18 months) and safe. In fact, during the follow-up period there were no deaths, nor opportunistic infections. Reintroduction of HAART was due to: CD4+ fall under 200/microl (6 cases), acute retroviral syndrome (4), individual choice (2), asymptomatic thrombocytopenia (1), peripheral neuropathy (1), pregnancy (1). A low CD4+ nadir level was correlated with a short period of treatment interruption.

Mycoplasma hominis and Ureaplasma urealyticum are frequently isolated from the cervical and vaginal tracts of HIV-negative asymptomatic women. Published data lack indisputable conclusions and doubts still exist as to whether these mycoplasmas are pathogens or mere co-factors associated with genital infections. We therefore conducted a surveillance study to investigate the prevalence of genital mycoplasmas in HIV-1 positive women (110 patients), attending the outpatient Infectious Diseases Clinic of our tertiary referral Hospital, by speculum examination, PAP test, endocervical and vaginal swabs obtained by gynaecologists. Ureaplasma urealyticum was isolated from the cervix of 45 women (41%). Mycoplasma hominis was recovered from 12 women (11%), in four of whom it was isolated at the same time from the vagina. PAP test results ruled out subclinical cervicitis in all women. Bacterial vaginosis, assessed by Amsel criteria and the Nugent score, was absent in all women. Our data show that the mycoplasmas in question are found in the lower genital tract of asymptomatic HIV-1-positive women at a frequency similar to that reported in the HIV-negative female population, and make a role for these microorganisms unlikely in the aetiology of cervico-vaginal infections also in this particular patient population.

Lipodystrophy in patients with HIV-infection has been studied intensively to understand its epidemiology and pathophysiology. Recently its development was attributed to a dysregulation of TNF-alpha synthesis' homeostasis by HAART. A few years ago it was found that pentoxifylline decreases TNF-alpha production. We describe one HIV-infected patient, with lipodystrophy syndrome, treated with pentoxifylline without any improvement of lipodystrophic symptoms.

We describe 2 most unusual cases of distal symmetrical painful polyneuropathy in patients with long-standing HIV-1 infection well controlled by HAART. Sural nerve biopsies revealed vasculitis in both cases and steroid therapy led to resolution of symptoms not influenced by analgesics and anti-inflammatory drugs. These unusual cases outline the importance of nerve biopsies in order to reach a diagnosis.

Whether highly active antiretroviral therapy (HAART) should be modified in patients with persistent increases in CD4(+) T cells despite detectable viral loads is an unresolved question. Forty-three heavily pretreated human immunodeficiency virus (HIV)-infected patients with virologic failure during HAART were studied before a change of therapy guided by genotypic analysis and during follow-up. Patients with an increase in CD4(+) cell count (>100 cells/ml) over pre-HAART values were considered to be discordant patients (20 individuals), whereas patients with a lower increase or no increase in CD4(+) cell count were considered failing patients (23 individuals). Based on univariate analysis, a high CD4(+) cell count before antiretroviral treatment, homosexual behavior as a risk factor for HIV infection, reduced drug exposure to nonnucleoside reverse transcriptase inhibitors, low replicative capacity of HIV isolates, and more frequent detection of HIV isolates with a non-B subtype, an R5 biological phenotype, and M184V and T215Y/F mutations were factors associated with a discordant response to HAART. Based on multivariate analysis, only the M184V mutation remained significantly associated with a viroimmunologic discordant response (odds ratio, 25.48; 95% confidence interval, 1.43 to 453.93). No difference in lamivudine exposure was found between discordant (95%) and failing (91%) patients. Twelve months after the genotypic analysis-guided change of therapy, 3 discordant (15%) and 6 failing patients (26%) achieved undetectable viral loads (<50 copies/ml), whereas in patients with HIV RNA loads of >500 copies/ml, discordant responses were observed in 5 out of 15 discordant patients and in 4 out of 16 failing patients. A relationship between the M184V mutation and a viroimmunologic discordant response to HAART was found. After the genotypic analysis-driven change of therapy, similar rates of virologic suppression were detected in the two groups.

In 32 patients for whom highly active antiretroviral therapy was failing, a good agreement between drug resistance-associated mutations in plasma and peripheral blood mononuclear cells (PBMCs) was found (k = 0.85). The mutations with the lowest agreement were 20R, 63P, and 84V in the protease gene and 184V in the reverse transcriptase gene. In eight patients, primary drug resistance mutations were detected only in PBMCs.

The fitness of human immunodeficiency virus (HIV) in vivo depends on the interaction of a multitude of viral and host factors. The aim of this study was to analyze the biological phenotype and the intrinsic capacity of the HIV isolates with drug-resistance mutations to replicate efficiently in the absence of drugs. An open label multicenter cross-sectional study was undertaken on 28 HIV-infected patients failing antiretroviral treatment. The subjects were studied for CD4+ cell count, HIV viral load, syncytium-inducing phenotype, genotypic drug-resistance assay, and replication capacity of HIV isolates assessed by co-culture assay. All HIV isolates showed a decreased replication capacity compared with wild-type strains. The lowest replication capacity was detected in HIV strains with more than five drug-resistance mutations. The highest replication capacity was observed in strains carrying the K103N and Y181C primary mutations that emerged after treatment with non-nucleoside analogue inhibitors. Isolates with R5 biological phenotype had a higher number of resistant mutations than X4 isolates (P = 0.004). Particularly, the R5 phenotype was detected in all 6 isolates with more than 14 drug-resistance mutations. Patients with R5 strains had plasma viral load similar to patients with X4 strains, but marginally higher CD4+ cell counts, and their HIV isolates had significantly lower replication capacity of HIV isolates (P = 0.008). No patient carrying HIV with a maintained replication capacity had a viral load less than 30,000 copies/ml. In patients failing HAART, the detection of HIV isolates with the R5 biological phenotype correlates with CD4+ cell count, an impaired replication capacity, and a high number of drug-resistance mutations., (Copyright 2003 Wiley-Liss, Inc.)

We studied factors associated with treatment adherence in 88 male and 21 female adults (age range, 24-65 years) with HIV infection undergoing therapy with HIV-1 protease inhibitors (PIs) in Italy. Data on sociodemographic variables, clinical and psychological symptoms, treatment compliance, physician/patient relationship, and psychosocial characteristics were obtained by means of semistructured interviews. Every subject also compiled two self-report questionnaires: Coping Orientations to Problem Experiences (COPE) and Medical Outcomes Study-HIV (MOS-HIV) in order to evaluate the use of coping strategies and quality of life. We found a high rate of adherence to HIV therapies (almost 90% of patients had taken at least 80% of medication in the previous 7 days). No significant differences were found between adherence and nonadherence groups as measured by self-report. Few significant differences were found when data laboratory were used. When a Bonferroni corrected p level of <0.001 was used, only a comparison on Mental Disengagement subscale of COPE was statistically significant.

To assess the circulation of human herpesvirus (HHV)-8 infection over the years, two seroprevalence surveys were conducted, which tested sera from HIV-infected individuals recruited 10 years apart (206 individuals from 1986 to 1988 and 177 individuals from 1997 to 1998). For all patients, antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV), and HHV-8 lytic and latent antigens were evaluated.HHV-8 seroprevalence was higher among individuals recruited in the 1990s (31.6% for anti-lytic, 8.5% for anti-latent antibodies) compared with similar findings in those seen in the late 1980s (14.6% and 3.4% for anti-lytic and anti-latent antibodies, respectively), with a twofold increase of the risk of HHV-8 infection. However, the increase was observed only among injecting drug users, whereas seroprevalence tended to slightly increase among those infected by sexual contact. At univariate analysis, time of recruitment and being homosexual men were factors associated with HHV-8 infection, an association that remained after adjusting for age. HBV infection was significantly associated with HHV-8 infection (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3-3.6), whereas those infected with HCV had a lower probability of having HHV-8 antibodies (OR, 0.3; 95% CI, 0.20-0.6). After controlling for age and gender, time of recruitment remained independently associated with HHV-8 infection among injecting drug users. In conclusion, HHV-8 seroprevalence appears to be increased during 10 years among HIV-infected injection drug users but not among homosexual men, who remain those at the highest risk of infection.