Unusual clinical manifestation and challenging serological interpretation of syphilis: insights from a case report.

BACKGROUND: The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus (HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times. CASE PRESENTATION: In 2020, a 52-year old HIV-positive bisexual male patient was admitted to our department with a 4-month history of moderately itchy cutaneous lesions localized at his neck, trunk and arms. In 2013, the patient presented with a classic syphilitic roseola of the trunk and a secondary syphilis was diagnosed, with increased levels of rapid plasma reagin (RPR), Treponema pallidum hemagglutination assay (TPHA), anti-Treponema pallidum IgM and IgG Index. A second episode occurred in 2018, as a primary syphilis with multiple ulcerative lesions of the penis, and increased levels of RPR, IgG and IgM. In 2019, a further episode of secondary syphilis was treated with Doxycycline. In 2020, erythematous and papular lesions with vesicular components and urticarial erythema multiforme (EM)-like lesions were present at the neck, trunk and arms. Serological tests and Nucleic Acid Amplification Test (NAAT) for Treponema Pallidum were performed, as well as a cutaneous biopsy with histological and immunohistochemical evaluation of one lesion. NAAT was negative for T. pallidum. Serological test results were discordant with a new syphilis infection, showing only increased levels of RPR and anti-Treponema IgG. The cutaneous biopsy revealed a non specific histological pattern, while the immunohistochemical evaluation with anti-spirochetal antibodies was mandatory for the diagnosis of recent syphilis, showing clusters of rod-shaped elements, some of which with spiral form, focally present at the epidermis and adnexal structures. CONCLUSIONS: Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.

Liver stiffness reduction and serum fibrosis score improvement in HIV/hepatitis C virus-coinfected patients treated with direct-acting antivirals.

OBJECTIVES: Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver stiffness and in serum liver fibrosis scores in HIV/HCV-coinfected patients before and after treatment with direct-acting antivirals (DAAs). METHODS: Liver stiffness measured using transient elastography as well as serum liver fibrosis scores [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated before and at 6-12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used. RESULTS: A total of 78 HIV/HCV-coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline [16.8 (interquartile range (IQR) 10.2-27.0) kPa at baseline vs. 9.4 (IQR 6.7-15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB-4 score [2.8 (IQR 1.5-4.8) vs. 2.0 (IQR 1.3-3.2), respectively; P < 0.01] and APRI [0.9 (IQR 0.5-2.2) vs. 0.4 (IQR 0.2-0.7), respectively; P < 0.01] was found. In univariate analysis, liver stiffness decrease was associated with increasing age, 'other' HCV genotype (vs. G1), the presence of cirrhosis, higher pre-DAA liver stiffness, sofosbuvir-based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB-4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA. CONCLUSIONS: A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV-coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow-up.

First-line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison.

OBJECTIVES: The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first-line regimens. METHODS: A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first-line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV-1 RNA copies/mL. Survival analyses using Kaplan-Meier (KM) curves and Cox regression with time-fixed covariates at baseline were employed. RESULTS: Overall, 1490 ART-naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30-43) years vs. 33 (IQR 27-39) years, respectively; P < 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257-421) cells/µL vs. 447 (IQR 347-580) cells/µL, respectively; P < 0.001] and a higher median viral load [4.38 (IQR 3.92-4.74) log10 copies/mL vs. 4.23 (IQR 3.81-4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89-5.80], for toxicity (RH 2.23; 95% CI 1.05-4.73) for intolerance (RH 5.17; 95% CI 2.66-10.07) and for proactive switch (RH 10.96; 95% CI 3.17-37.87) than those starting RPV. CONCLUSIONS: In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.

Pre-existent NRTI and NNRTI resistance impacts on maintenance of virological suppression in HIV-1-infected patients who switch to a tenofovir/emtricitabine/rilpivirine single-tablet regimen.

Objectives: To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes). Methods: pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated. Results: Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P < 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P < 0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; <100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia >500 000 copies/mL were independent predictors of VR by multivariable Cox regression. Conclusions: TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.

Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens.

OBJECTIVES: We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. METHODS: Data from 206 drug-naïve and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. RESULTS: DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naïve and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naïve patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1-10.3) months; 100 000-500 000 copies/mL: median (IQR) 4.9 (3.8-6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5-4.8) months; P < 0.001] and in PI-experienced patients [≥100 000 copies/mL: median (IQR) 7.2 (5.7-11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4-3.3) months; P < 0.001]. In PI-experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug-naïve: 95%; PI-experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800. CONCLUSIONS: In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.

Reduced risk of Efavirenz Discontinuation in Naïve Patients Starting First-Line Antiretroviral Therapy with Single Tablet versus dual Tablet Regimen.

OBJECTIVES: Despite not being approved in Europe as first-line therapy, the efavirenz (EFV)-containing single tablet regimen (STR) is frequently used in clinical practice in naïve patients but few data are available on this strategy. In our study, we aimed to assess the risk of EFV discontinuation in patients starting antiretroviral therapy with STR vs. nonSTR. METHODS: This was a multicentre study retrospectively enrolling naïve patients starting EFV+TDF+FTC. Patients were followed from the time of treatment initiation to the discontinuation of the EFV-containing regimen, comparing STR vs. nonSTR. Two different analyses were performed: (A) nonSTR patients censored at the last observation (switch to STR not considered as the end of observation); (B) nonSTR patients censored at the time of switch to STR. RESULTS: The study included 235 patients, of whom 74 (31.5%) directly started STR. Among patients starting nonSTR, 108 (67.1%) switched to STR after a median period of 6 months. Forty-four EFV discontinuations were observed (13 among STR vs. 31 among nonSTR patients). The overall estimated probability of discontinuation was 30% at 5 years, about half (14.8%) of these occurring during the first year. Analysis A did not show significant differences between STR and nonSTR regarding the probability of efavirenz discontinuation (19.9% vs. 24.7% at 5 years, P = 0.630). In contrast, Analysis B showed that the probability of EFV discontinuation was similar (8.3%) between STR and nonSTR patients up to 8 months. Thereafter, a significantly higher rate of discontinuation was observed in nonSTR patients (47.5% vs. 19.9% at 5 years, P = 0.034). CONCLUSIONS: Our data suggest that an early switch to STR during the first months of treatment could reduce the risk of EFV discontinuation.

Maraviroc 150 mg daily plus lopinavir/ritonavir, a nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimen for HIV-infected naive patients: 48-week final results of VEMAN study.

Non-conventional strategies with nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens in antiretroviral naive human immunodeficiency virus (HIV) -infected patients have been explored in clinical trials. A prospective, open-label, randomized (1:1), multicentre, proof-of-concept trial (VEMAN study, EUDRACT number 2008-006287-11) was conducted assigning HIV-infected naive patients to once-daily maraviroc plus lopinavir/ritonavir (MVC group) or to tenofovir/emtricitabine plus lopinavir/ritonavir (TDF/FTC group). Clinical and laboratory data were collected at baseline, and after 4, 12, 24, 36 and 48 weeks with the objective to evaluate the 48-week virological and immunological efficacy. HIV-1 DNA load and CD4(+) T-cell subsets were analysed on frozen peripheral blood mononuclear cells collected at baseline, 4 and 48 weeks to explore the trend in HIV reservoirs. Fifty patients were randomized and included in the analysis. During follow up, HIV-1 RNA decreased similarly in both groups and, at week 48, all patients in the MVC group and 22/24 (96%) in the TDF/FTC group had < 50 copies/ml of HIV-1 RNA. CD4(+) trend during follow up was higher in maraviroc-treated patients (MVC group: 286 (183-343) versus TDF/FTC group: 199 (125-285); Mann-Whitney U-test: p 0.033). A significant 48-week increase of CCR5(+) CD4(+) T cells and CD4(+) effector memory cells was observed among maraviroc-treated patients (Wilcoxon signed rank test: p 0.016 and p 0.007, respectively). No significant variations were found in naive and central memory CD4(+) T cells. Among naive patients with an R5 virus, treatment with maraviroc and lopinavir/ritonavir was shown to provide a virological response compared to a triple therapy and a greater immunological benefit.

Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis.

INTRODUCTION: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. RESULTS: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. DISCUSSION: The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. CONCLUSION: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon.

Effect of suppressing HIV viremia on the HIV progression of patients undergoing a genotype resistance test after treatment failure.

BACKGROUND: Treatment guidelines for multi-experienced HIV patients have recently evolved from aiming to preserve immunity to achieving virological success, largely due to the availability of new antiretroviral drugs and drug classes. To assess the role of viral suppression on clinical progression following a genotypic resistance test (GRT), we have examined a database on patients failing to respond to combined antiretroviral therapy (cART). METHODS: Patients undergoing a GRT after failure to respond to cART between January 1999 and May 2006 were followed up to December 2006. Time-to-death or a new AIDS event/death were considered to be analysis end-points. Viral suppression (< 50 copies/ml [c/ml]) after GRT, a time-dependent covariate, was tested as predictor of disease progression. RESULTS: Overall, 1,389 patients were included in this observational study. After the GRT, patients were followed up to 72 months (median 28 months, IQ range 13-51 months). During the follow-up, 124 patients (9%) died, and 86 (6%) experienced a new AIDS event. 774 patients (56%) achieved < 50 c/ml HIV-RNA. The results of an adjusted Cox model showed that undetectable HIV-RNA after the GRT was significantly associated with a lower risk of death (hazard ration [HR] 0.46, 95% confidence interval [CI] 0.27-0.76) and AIDS/death (HR 0.43, 95% CI 0.28-0.65). The adjusted hazard ratios suggested a twofold risk reduction. A threefold risk reduction of death related to achieved undetectable viral load was found in patients with resistance to more than one drug class and with CDC-C diagnosis; a fourfold reduction was found in patients with < 200 CD4+/mm(3). CONCLUSIONS: Maximal viral suppression has a large impact on HIV progression, particularly in heavily pre-treated individuals. Our findings support the latest treatment guidelines, which have rapidly evolved from an initial lack of indication to suggestions, and finally to strong recommendations for achieving the goal of suppressing viremia.

Evidence of dual sexual transmission of multi-resistant HIV with two years persistence of resistance to NRTI and NNRTI: a case report.

A case report of dual sexual transmission, with secondary transmission from naïve to naïve patient, of HIV harbouring K103N and L100I mutations, conferring full non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, plus 2 nucleoside analogous reverse transcriptase inhibitor (NRTI) mutations is described. The secondary transmission of the resistant virus was confirmed by phylogenetic analysis. Data also suggest that mutations related to NRTI and NNRTI resistance may persist for a long time in naive patients, over 2 years in the present case report.

Observational study on HIV-infected subjects failing HAART receiving tenofovir plus didanosine as NRTI backbone.

We evaluated the efficacy of tenofovir (TDF) - and didanosine (ddI)-containing backbones in HIV-infected experienced subjects. We included in the study 245 subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log(10) cp/ml and an available genotypic resistance test at baseline. At baseline, median CD4 counts and HIV-RNA were 278 cell/mmc and 4.32 log(10) cp/ml, respectively. Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug-related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66, 95% CI: 0.54- 0.79, p < 0.001 for each additional log(10) copies/ml), and the total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI: 0.81-0.92, p < 0.001 for each additional mutation) were both predictors of virologic success. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic success (increase of > or = 100 cells/mm(3) from baseline) in a median time of 7.5 months; immunologic success was associated with HIV-RNA levels at baseline (HR: 0.91, 95% CI: 0.79-0.98, p = 0.04 for each additional log(10) copies/ml), the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85-0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11, 95% CI: 1.00-1.23, p = 0.05 for each additional 100 cells/mm(3)). Results obtained by the on-treatment analyses were comparable. In our study, HAART containing TDF/ddI seem associated with a virologic and immunologic response, when such regimens are chosen according to a genotypic resistance test.

Changes in regular condom use among immigrant transsexuals attending a counselling and testing reference site in central Rome: a 12 year study.

OBJECTIVE: To analyse data from male to female transsexuals attending between 1992 and 2003 an outpatient clinic considered the main HIV counselling and testing site in Rome for foreign people. METHODS: Data collected between 1992 and 2003, from a routine anti-HIV testing and counselling activity, were analysed. A brief standard interview was performed at each test. A cross sectional analysis to assess the association of regular condom use with demographic and behavioural variables using multiple logistic regression was performed. A follow up analysis to define the effect of single factors on the occurrence of new anti-HIV seroconversions was also performed. The incidence of anti-HIV seroconversion was calculated in person years of observation. RESULTS: Overall, 473 transsexuals sex workers were tested. Most of them (99%) were from South America (mainly Columbia and Brazil). Anti-HIV prevalence was 32%, but a progressive decrease over time was observed (from 57% in 1993 to 12% in 2003). The proportion of patients reporting regular condom use at enrolment was 75%. A progressive increase in regular condom use was reported over time (from 43% in 1992-3 to 79% in 2002-3). 15 new HIV infections were observed during follow up (incidence 2.1 per 100 person years). Though the proportion of patients reporting regular condom use increased over time, 10 out of the 15 new infections occurred in patients reporting unprotected sex during follow up (rate 8.4 per 100 person years). CONCLUSIONS: Our data suggest that counselling may lead to an increase in safe sex practices among immigrant transsexuals. However, the incidence of new HIV infections is still high and mainly related to non-regular condom use, which still remains the primary objective of prevention.

Factors related to virologic failure among HIV-positive injecting drug users treated with combination antiretroviral therapy including two nucleoside reverse transcriptase inhibitors and nevirapine.

Treatment strategies in human immunodeficiency virus (HIV)-positive active injecting drug users (IDUs) must take into account their lifestyles, that often result in low adherence to therapy. The nonnucleoside reverse transcriptase inhibitors (NNRTI) offer simpler treatment regimens, but the appearance of drug resistance during treatment failure may cause high levels of cross-resistance to all NNRTIs. We adopted a combination therapy of two NRTIs and nevirapine (NVP) for treatment of IDU patients to evaluate its feasibility in such patients. From October 1998 to December 1999, demographic, clinical, and laboratory data from 80 IDUs on this regimen were collected. Fisher's exact test, Kaplan Meier method, and Cox model were used for statistical analysis. Overall, 20 IDUs discontinued the treatment because of side effects and 20 IDUs experienced treatment failure. Considering the treatment failure as an end point, 55.6% (95% confidence interval [CI]: 37.9%-72.6%) of patients was still undergoing treatment after 12 months compared to 44.6% (31.8%-58.6%) when discontinuation was also taken into account. An increasing trend over time was observed in the CD4+ lymphocyte count, among failing and nonfailing IDUs. By multivariate analysis, baseline HIV-RNA, treatment breaks and low adherence and active injecting drug use turned out to be significantly associated with treatment failure. Our results show that continuing injecting drug use and treatment breaks are the main factors that can lead to treatment failure in IDUs and easily to NNRTI class resistance.

Female sex and the use of anti-allergic agents increase the risk of developing cutaneous rash associated with nevirapine therapy.

To identify factors associated with cutaneous rash, we performed a retrospective multicentre analysis of HIV outpatients starting a highly active antiretroviral therapy regimen containing nevirapine. A total of 62 cutaneous adverse events were observed in 429 patients. Rash hazard was increased in women, by the prophylactic use of glucocorticoids or antihistaminics, and was reduced by escalating the initial dose of nevirapine. Women receiving glucocorticoids had a 3 month cumulative probability of rash of 0.41.

HIV infection among foreign transsexual sex workers in Rome: prevalence, behavior patterns, and seroconversion rates.

BACKGROUND: The Azienda Sanitaria Locale Roma E (ASL-RME) outpatient clinic is the main reference center in Rome for HIV testing of foreign people. GOAL: To define the prevalence and incidence of HIV infection among foreign transsexual sex workers attending the center. STUDY DESIGN: A cross-sectional, follow-up study was conducted. RESULTS: Between 1993 and 1999, 353 transsexuals attended the ASL-RME. They were from Colombia (n = 208), Brazil (n = 122), and other countries (n = 23). Most of these transsexuals reported having 5 to 10 partners per day. The overall HIV prevalence was 38.2%, which multivariate analysis found to be associated with origin from Brazil and a higher number of sex partners. The observed HIV seroconversion rate was 4.1 per 100 person-years, and non-regular condom use was the only factor related to seroconversion. CONCLUSIONS: The data from this study suggest that promotion of safer sex practices and regular condom use still is the main priority among marginalized population subgroups, such as foreign prostitutes, involved in sex activities that put them at risk for HIV infection.

Response to highly active antiretroviral therapy according to duration of HIV infection.

OBJECTIVE: To evaluate whether duration of HIV-1 infection influences the response to highly active antiretroviral therapy (HAART). DESIGN: Prospective study of individuals (Italian Seroconversion Study cohort) with well-estimated dates of HIV-1 seroconversion. METHODS: This analysis included 277 participants who began HAART (defined as three antiretroviral drugs used in combination). Cox regression models were used to evaluate the association between duration of infection (as categorical variable [7.5 years from seroconversion] or continuous variable) and an immunologic (rise in CD4 count >100 cells/mm3) and a virologic (decline in plasma HIV-RNA to unquantifiable levels) outcome. All analyses were stratified by center of recruitment and adjustment, when used, was for gender, age at inception of HAART, injection drug use, previous antiretroviral therapy, lag-time between positive and negative HIV test result, year of starting HAART, clinical stage, CD4 count, and HIV-RNA at time of HAART. RESULTS: HAART was initiated a median of 6.4 years after seroconversion. There was a median follow-up of 1.6 years after starting HAART to the calendar cut-off (November 1999). One-hundred-eighty-one (65.3%) patients experienced a decline in viral load to below quantifiable levels and 184 (66.4%) experienced a rise in CD4 >100 cells/mm3. In the Cox models, by 1-year increase in duration of infection, we estimated a lower crude hazard of achieving a CD4 count increase >100 cells (relative hazard [RH], 0.96; 95% confidence interval [CI], 0.92-1.01; p =.09), and a lower hazard of reaching an unquantifiable level of plasma HIV-RNA (RH, 0.97; 95%CI, 0.93-1.02; p =.20). After adjustment, these values became 0.99 (95%CI, 0.93-1.04; p =.62) and 0.98 (95%CI, 0.93-1.04; p =.48), respectively. When duration of HIV infection was considered as a categorical variable, the results were consistent with those already described. CONCLUSIONS: These results suggest that the duration of HIV infection does not seem to play an important independent role in determining the virologic and immunologic responses to HAART.

Dynamics of viral load in plasma and HIV DNA in lymphocytes during highly active antiretroviral therapy (HAART): high viral burden in macrophages after 1 year of treatment.

In this study we evaluated the level of HIV RNA in plasma and HIV DNA in peripheral blood cells. Sixteen antiretroviral-experienced HIV patients with severe immune suppression were included in the study. After the first month, 56.2% of the patients showed undetectable levels of HIV RNA, this percentage remaining stable after 1 year (53.3%). At enrollment, 7 patients (43.7%) with a low CD4+ T cell count (mean 22 per mm3 versus 73) showed HIV DNA levels below the limit of detection (5 copies/10(5)) in lymphocytes. They all subsequently had increased HIV DNA that became detectable between the first and the third month of therapy, associated with an increase of the CD4+ T cell count (mean 22 to 95/mm3); in 4 of these patients this increase was transitory, becoming undetectable again after one year. In 7 out of the 8 patients with detectable HIV DNA at enrollment, the HIV DNA level decreased over time. Seven out of 15 patients at 1 year (46.7%) showed both undetectable levels of HIV RNA in plasma and HIV DNA in lymphocytes (p<0.05); these patients had a higher CD4+ T cell count at baseline (mean 75 versus 25/mm3) and a higher increase (306 versus 177/mm3) after 1 year. PCR-based dilution assay carried out at 1 year showed that all patients had a consistent amount of HIV DNA positive- CD4+ T lymphocytes and macrophages, with higher values in these last cells. The data indicate that a durable reservoir of virus is still present in both lymphocytes and monocytes, even after long-lasting HAART treatment.