The Management of Geriatric and Frail HIV Patients. A 2017 Update from the Italian Guidelines for the Use of Antiretroviral Agents and the Diagnostic Clinical Management of HIV-1 Infected Persons.

OBJECTIVE: This article deals with the attempt to join HIV and geriatric care management in the 2017 edition of the Italian guidelines for the use of antiretrovirals and the diagnostic-clinical management of HIV-1 infected persons. METHODS: The outlined recommendations are based on evidence from randomized clinical trials and observational studies published in peer-reviewed journals and/or presented at international scientific conferences in recent years. The principles of starting antiretroviral therapy in elderly patients and the viro-immunological goals are the same as in the general HIV population. However, there are some specificities to consider, related to the host as well as the therapy itself. HIV care in elderly patients must shift from a combined AntiRetroviral Therapy specific approach to a more comprehensive management, and from a disease-based model (list of co-morbidities) to a multi-morbidity and frailty standpoint. The implementation of a geriatric approach, based on the Comprehensive Geriatric Assessment, is essential and consists of a broader evaluation of health status. This multidimensional and multidisciplinary evaluation is focused on the development of a tailored intervention plan. Polypharmacy is a frequent condition in the older population and an independent risk factor for negative health-related outcomes. This can be overcome with a multidisciplinary and cooperative approach involving HIV specialists, geriatricians and primary care physicians. CONCLUSION: The inclusion of geriatric care becomes necessary due to the novel needs of an evolving patient population. It is important to underline that the HIV specialist will continue to lead multidimensional interventions and optimize quality of care for HIV-positive people.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Successful treatment of Cryptococcal meningitis with a combination of liposomal amphotericin B, flucytosine and posaconazole: two case reports.

Cryptococcus neoformans CNS infection frequently affects HIV-infected patients and is often lethal, despite antifungal therapy. The most recent treatment guidelines for Cryptococcal meningitis recommend therapy with lyposomal amphotericin B and possible association with flucitosine. However, clinical response rates in HIV-infected patients are not satisfactory, with a persistent high mortality rate and long term therapy is affected by a high risk of major side effects. Posaconazole, the latest broad-spectrum azole, with both in vitro- and in vivo-documented potent activity against C. neoformans, clearly showed no antagonism with amphotericin B, echinocandins or flucytosine and it has both in vitro and in vivo agonistic activity with flucytosine against C. neoformans. We report two cases of successful salvage therapy based on the addition of posaconazole to a standard treatment based on liposomal amphotericin B and Flucytosine. In addition we used posaconazole also in a maintenance therapeutic regimen with no evidence of recurrences in the follow up of these patients. Our report confirms that posaconazole has clinical activity in the CNS against C. neoformans infection. In addition posaconazole showed no antagonism with any other currently available antifungal agent, and was in fact synergistic to some of them (flucytosine); consequently, it seems to be an ideal candidate for antimicrobial combination salvage therapies. Finally posaconazole represents a good alternative to parenteral therapy and an ideal candidate for long-term maintenance therapy due to its competent toxicity profile and oral bioavailability.

Penetration of didanosine in semen of HIV-1-infected men.

OBJECTIVES: The disposition of antiretroviral agents into genital tissue and fluids is one of the factors implicated in the control of viral replication within the male genital tract and should be an objective of highly active antiretroviral therapy. We have investigated didanosine penetration in seminal plasma of 16 HIV-infected patients. PATIENTS AND METHODS: A total of 16 patients on didanosine (200 mg every 12 h or 400 mg once daily) participated in the pharmacokinetic study. After the didanosine morning dose, peripheral blood plasma and semen plasma were collected within the intervals 0-4, 4-8 and 8-12 h in the twice-daily regimen and 0-4, 4-12 and 12-24 h in the once-daily regimen. RESULTS: Within each sampling time interval didanosine concentrations in seminal plasma were higher than in blood. The interquartile range of concentrations in seminal plasma was 292-1217 ng/mL, compared with 50-150 ng/mL in blood plasma. Didanosine could be detected in 14 of the 16 semen samples analysed and in 8 of the 16 blood samples. CONCLUSIONS: We have demonstrated that didanosine penetrates into the seminal plasma in higher concentrations than in blood plasma.

Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study.

OBJECTIVES: To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients. METHODS: Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures. RESULTS: Among 58 virological responder patients (> or =1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of< or > or =100 cells/microL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow-up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32-20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45-57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27-64.01; P<0.001) correlated with highly significant immune recovery. CONCLUSIONS: These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.

Quality of life assessment in HIV-positive persons: application and validation of the WHOQOL-HIV, Italian version.

QoL assessment is currently considered essential for clinical trials in HIV infection, as commonly used end-points (CD4 level, viral load, opportunistic diseases) are inadequate to catch the complexity of treatment outcomes. The World Health Organization has recently developed a standardized set of instruments to assess subjective quality of life (QoL) in different medical conditions, including HIV infection. Here we report evidence for the acceptability, reliability and validity of the Italian version of the WHOQOL-HIV. The Italian version of WHOQOL-HIV has been administered in a sample of 151 HIV-positive persons, consecutively attending the largest infectious diseases hospital in southern Italy. Mean time of administration and percentage of missing responses, Cronbach alpha, Pearson coefficient and oneway ANOVA were applied to assess, respectively, acceptability, reliability, convergent and disciminant validity, and sensitivity to change. Mean time of administration was 28 minutes; only 2 questionnaires showed more than 20% of missing responses. Cronbach alpha was above 0.70 in 22 of the 28 sections of the WHOQOL-HIV; it ranged between 0.53 and 0.68 in the remaining 6 sections. Each of the 7 QoL principal domains correlated with overall QoL at a significance level p < 0.001. Moreover, correlation between principal domains were always statistically significant (p < 0.01) with only two exceptions. Finally, mean scores in each QoL domain were in the expected direction (worse in AIDS patients as compared to asymptomatic and symptomatic persons). The Italian version of WHOQOL-HIV is a valid and reliable instrument to assess subjective QoL in HIV-positive persons. It seems potentially useful to assess patients' life satisfaction, and to calibrate standards of care in different stages of the infection.

Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals.

The risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and protease inhibitors (PIs) respectively. Thymidine associated mutations were identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2), 215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the changes associated with resistance to lamivudine (184V or 118I). No non nucleoside-RTI (NNRTI) mutations were present in the study period. Primary PIs mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note, mutations related to resistance to more than one class of antiretrovirals were present in one (1.5%). Among patients with chronic infection a large proportion (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4 patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). Primary mutations associated with substantial resistance to PIs were found in only 5/347 patients (1.4%); all the other patients carried only secondary mutations. Prevalence of mutations associated with high-level resistance to antiretroviral drugs is stable in recently infected individuals and low in patients with established HIV infection. The potential impact of transmitted mutations on the response to first regimen in individuals carrying transmitted mutations needs to be assessed by prospective studies.

Immunohistochemical expression of cyclin T1 in a case of AIDS-related cachexia.

The expression of cyclin T1 in an autoptic case of AIDS-related cachexia was investigated by immunohistochemistry. When contrasted with normal human tissues, a very similar pattern of expression was found. However, a peculiar distribution of cyclin T1 was noticed in the brown fat and in lymph nodes affected by AIDS-associated lymphadenopathy.

Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.

BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse. METHODS: This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.

Premature lesions of the carotid vessels in HIV-1-infected patients treated with protease inhibitors.

OBJECTIVES: To evaluate the presence of premature atherosclerotic lesions of epiaortic vessels in HIV-1-infected protease inhibitor-(PI) treated patients compared with PI-naive patients and healthy individuals. DESIGN: One-hundred and two HIV-1-positive patients, including 55 treated with PI for at least 12 months and 47 either naive or treated with PI-sparing regimens, were subjected to epiaortic vessel ultrasonography. These data were compared with those obtained from 104 healthy individuals. METHODS: Intima characteristics, pulsation and resistance indexes, and minimal, peak and mean speed were evaluated using a colour power doppler. Atherosclerotic plaques were described. Independent risk factors and values for glycaemia, cholesterolaemia and triglyceridaemia were considered. Statistical analysis included the chi-square test, Mantel-Haenszel test, odds ratio and logistic regression analysis. RESULTS: Of the PI-treated patients, 29 out of 55 (52.7%) presented acquired lesions of the vascular wall at ultrasonography, whereas similar lesions were found in seven out of 47 (14.9%) PI-naive patients. Of the 104 healthy individuals, seven cases (6.7%) of intimal medial thickness were noted. A slightly significant correlation was found between carotid lesions and age, male sex and hypercholesterolaemia, whereas cigarette smoking, hypertriglyceridaemia and Centers for Disease Control and Prevention stage significantly increased the risk of vascular lesions (P= 0.022, P= 0.017 and P= 0.079 respectively). However, the highest significance regarded use of PI (P= 0.011). These results were confirmed by logistic regression analysis. CONCLUSIONS: These data demonstrate a higher than expected prevalence of premature carotid lesions in the PI-treated compared with PI-naive patients. If confirmed, a periodic ultrasonographic study of the vascular wall should be included in the follow-up of HIV infected patients.

A combination of nucleoside analogues and a protease inhibitor reduces HIV-1 RNA levels in semen: implications for sexual transmission of HIV infection.

Direct contact with semen is the major route of sexual acquisition of human immunodeficiency virus (HIV) in homosexual and heterosexual partners of seropositive men. In this study, we show that concentrations of HIV-1 RNA molecules in plasma and semen of seropositive patients are related to the duration and type of antiretroviral agents used in treatment. In patients treated with zidovudine alone, 1, 3 and 6 months after the start of therapy, the mean HIV-1 load in plasma was reduced by 0.57, 0.38 and 0.21 log10 and in semen by 0.66, 0.50 and 0.15 log10, respectively. In patients treated with zidovudine plus didanosine at months 1, 3 and 6, the mean decrease in plasma HIV-1 RNA was 1.40, 1.25 and 1.12 log10 and in semen 1.10, 1.41 and 1.32 log10, respectively. In patients treated with a combination of a protease inhibitor and two nucleoside analogues the mean log10 decrease was 1.77, 1.83, 1.71 and 2.38 log10 in plasma and 1.17, 1.74, 2.19 and 3.02 log10 in semen at 1, 2, 3 and 4 months, respectively. Treatment with a combination of a protease inhibitor and two nucleoside analogues caused a dramatic decrease in cell-free HIV-1 RNA in semen, which is a reliable measure of viral load. These findings could have implications for the sexual transmission of HIV-1.

Comparison of once and twice daily dosing of didanosine in combination with stavudine for the treatment of HIV-1 infection. AI 454-146 Team.

OBJECTIVE: To compare the antiviral activity, safety and tolerability of didanosine dosed once and twice daily when administered in combination with stavudine dosed twice daily in human immunodeficiency virus type 1 (HIV-1)-infected individuals with little or no previous exposure to antiretroviral drugs. DESIGN: Comparative, multicentre, randomized, open-label, short-term study. PATIENTS AND METHODS: Eighty-four HIV-1-infected adults with qualifying baseline CD4 cell counts of 200 to 500 cells/mm3 were included in the study. Of these, 43 patients received once daily didanosine plus twice daily stavudine (group A) and 41 subjects received twice daily didanosine plus twice daily stavudine (group B). The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens of variations in plasma HIV-1 RNA levels from baseline over the first 12 weeks of therapy. Plasma HIV-1 RNA levels, CD4 cell counts and adverse events were monitored. RESULTS: At week 12, median HIV-1 RNA variations were -1.18 log10 copies/ml in group A and -0.88 log10 copies/ml in group B. For patients who were followed up to week 24, median variations of HIV-1 RNA levels from baseline were -1.21 log10 copies/ml in group A and -0.78 log10 copies/ml in group B. The TAD between the two treatment groups for variations from baseline plasma HIV-1 RNA levels over the first 12 weeks was 0.10 log10 copies/ml (95% confidence interval, -0.19 to 0.40), indicating equivalence. CONCLUSION: Once daily didanosine plus twice daily stavudine and twice daily didanosine plus twice daily stavudine are equally effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts. Both regimens are safe and well tolerated.

Rare mutations in a domain crucial for V3-loop structure prevail in replicating HIV from long-term non-progressors.

OBJECTIVE: To evaluate the role of the selective forces exerted by the host on the HIV-1 structures involved in viral entry. DESIGN AND METHODS: The V3 region of the env gene was analysed in cell-free HIV-1 RNA from 17 infected subjects: 11 long-term non-progressors (LTNP) and six symptomless, typical progressor patients. To evaluate the potential biological significance of one of the rare variants detected in the LTNP, it was reproduced by recombinant PCR into a HIV-1 molecular clone. RESULTS: The intrapatient divergence of the V3-loop sequences averaged 8.62% in LTNP and 5.29% in progressors, although LTNP displayed lower divergence from the clade B consensus than progressors (16.65 and 19.76%, respectively). The analysis of non-synonymous and synonymous substitutions indicated that selective pressure was exerted in this region in both LTNP and progressors. Individual peculiarities (unique and rare V3-loop variants) emerged, however, in most sequences from LTNP, and variants bearing mutations in a domain crucial for the V3-loop structure were more prevalent in LTNP (P = 0.0012). The pNL4-3-derived mutant reproducing a V3-loop variant detected in a LTNP was efficiently expressed upon transfection, but the mutant virus was nearly completely unable to infect CD4+ cell lines, activated primary peripheral blood lymphocytes, or monocyte-derived macrophages, suggesting that a defect impaired the entry phase of the replication cycle. CONCLUSIONS: The results indicate that host factors impose selective constraints on the evolution of the HIV-1 structures involved in viral entry. In LTNP, these factors are likely to force the virus into attenuated variants.

90K (Mac-2 BP) predicts CD4 decline in human immunodeficiency virus-infected patients with CD4 counts above 200 x 10(6) cells/L.

OBJECTIVE: To evaluate the ability of serum levels of 90K, previously reported as a progression marker of human immunodeficiency virus infection, to predict the future rate of CD4 lymphocyte decline. DESIGN: Retrospective analysis of data from outpatients enrolled in a multi-institutional study. PATIENTS: One hundred five human immunodeficiency virus-positive intravenous drug users who had at least six serial CD4 lymphocyte measurements and starting CD4 levels of 200 x 10(6) cells/L or higher. MAIN OUTCOME MEASURE: Rate of CD4 lymphocyte decline. RESULTS: During a median follow-up of 28 months (range, 20-36 months), the estimated loss of CD4 cells in the whole patient population was 3.4 x 106 cells/L per month (P = .0045). Subjects who were on zidovudine treatment at study entry showed an average loss of 3.8 x 10(6) cells/L per month, significantly higher than in untreated subjects (P = .02), but similar to the loss observed for those requiring initiation of treatment during the course of the study. At baseline, 56 subjects had 90K levels of 10 microg/mL or less, and 49 had more than 10 microg/mL. The rate of CD4 decline in the high-90K group was approximately 5 x 10(6) cells/L per month (P < .0015), whereas in the low-90K group it was not different from zero (P = ns). No difference emerged in the rate of CD4 decline when subjects were stratified according to baseline 90K levels and zidovudine treatment, beta2-microglobulin, or neopterin serum levels. CONCLUSION: 90K serum levels are predictive of CD4 decline.

[Rhodococcus equi pneumonia in AIDS: a case report] / Polmonite da Rhodococcus equi in un soggetto on AIDS: descrizione di un caso clinico.

We describe the first case, in Campania, of Rhodococcus equi pneumonia in an HIV positive subject. The clinical symptoms resolved after antibiotic therapy. The pulmonary lesion at 10 months of radiological follow up results just partially reduced in its diameters.

Analysis of HIV-1 load in blood, semen and saliva: evidence for different viral compartments in a cross-sectional and longitudinal study.

OBJECTIVES: To quantify the HIV-1 load (measured as copies of viral RNA/ml using competitive reverse transcription-polymerase chain reaction) in blood, semen and saliva and to look for relationships between the viral burden, the clinical and immunological status and antiretroviral therapy. METHODS: Peripheral blood, semen and whole saliva samples were collected from 26 anti-HIV-1-seropositive patients selected for a cross-sectional study. Nine of the 26 patients provided samples of the three biological fluids for a longitudinal study. RESULTS: HIV-1 RNA was detected in 26 out of 26 samples of plasma, in 25 out of 26 samples of semen and in 24 out of 25 samples of saliva. The median number of HIV-1 copies in plasma was 14 817/ml (range: 167-254 880), in semen was 515/ml (range: 0-196 050) and in saliva was 162/ml (range: 0-72 080). The viral load in semen and in saliva was significantly lower than in plasma (P < 0.0001). The HIV-1 RNA levels in plasma and in saliva were correlated (P < 0.05), but levels in semen were not correlated with either plasma or saliva levels. The HIV-1 copy number in plasma was significantly higher in symptomatic patients than in asymptomatic subjects (P < 0.05). Plasma and saliva HIV-1 RNA levels were higher in subjects with a CD4+ cell count < 200 x 10(6)/l than in subjects with a CD4+ cell count > 200 x 10(6)/l (P < 0.05). The HIV-1 RNA load in either plasma, semen or saliva is not related to antiretroviral therapy. CONCLUSIONS: The absence of a correlation between plasma and semen loads suggests that semen and blood are distinct viral compartments. Viral load in semen is not related to the clinical stage of HIV infection or to the CD4+ lymphocyte count. Consequently, HIV-1-infected subjects are potentially infectious at all stages of immuno-deficiency and adequate precautions must always be taken to prevent the sexual transmission of HIV.

The 90K tumor-associated antigen and clinical progression in human immunodeficiency virus infection.

We investigated the possibility that a secreted glycoprotein of approximately 90,000 daltons, termed 90K and identified as a member of the protein superfamily characterized by the scavenger receptor cysteine-rich (SRCR) domain, might have value as a predictor of progression to acquired immunodeficiency syndrome (AIDS) in subjects infected with the human immunodeficiency virus (HIV). Among 488 HIV-seropositive intravenous drug users with a median follow-up of 32.5 months, high levels of serum 90K at baseline proved to be a significant predictor of faster progression to AIDS, either as a continuous variable (log 90K; p < 0.0001) or as a dichotomous variable with an optimized cutoff point of 30 U/ml (p < 0.00001). Analysis of 90K in relation to known prognostic factors found an association with CD4 count, beta 2-microglobulin, and p24 antigen but none with neopterin. In multivariate analysis, the baseline 90K level was an independent predictor of AIDS. As compared with subjects with low levels of 90K, the relative risk of developing AIDS was 3.5 (95% CI 1.9-6.5) among those with high levels of 90K. The predictive value of 90K was maintained after stratification by baseline CD4 count: among subjects with > or = 500 x 10(6)/L CD4 cells, the proportion in whom AIDS developed was 10.5% for those with 90K levels < or = 30 U/ml as compared with 20% for those with 90K above the cutoff point (p = 0.006). Serum 90K is an independent predictor of the risk for progression to AIDS in HIV-infected subjects, including those whose CD4 counts have not fallen.