COPEDOL: A two-year observational study in pretreated HIV-1-infected patients switching to a dolutegravir-based regimen.

OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer inhibitor of particular interest as a rescue treatment for people living with HIV (PLWHIV) who develop resistance to multiple antiretrovirals (ART). We assessed the virological treatment response in patients switched to a dolutegravir-based regimen following failure of previous ART treatment in a real-world treatment setting. PATIENTS AND METHODS: This was a multicenter, longitudinal, observational study with retrospective patient enrolment. Patients were enrolled between February 2017 and January 2018. Patients starting dolutegravir treatment between February 2014 and September 2016 were retrospectively included. Patients were followed up for 24 months after dolutegravir initiation. During this period, treatment with dolutegravir could be discontinued at any time at the physician's discretion. Treatment failure was either defined as a viral load≥50 copies/mL at two consecutive blood samples or as clinical or biological safety issues. Overall, 459 patients were enrolled and 329 completed 24 months of treatment. The primary study outcome measures were treatment response and time to treatment response. RESULTS: 346/440 patients (78.6%) achieved a treatment response; 86 patients discontinued dolutegravir treatment (of whom 17 for failure to achieve or maintain viral suppression and 38 for tolerability issues). Acquired dolutegravir-resistance mutations were identified in five patients. CONCLUSIONS: A sustained treatment response can be obtained with a dolutegravir-based treatment regimen in PLWHIV experiencing treatment failure, even in vulnerable patients with a long history of previous ART failure, infected with multidrug-resistant HIV strains, and with multiple comorbidities.

Nonlinear wavefront reconstruction with convolutional neural networks for Fourier-based wavefront sensors.

Fourier-based wavefront sensors, such as the Pyramid Wavefront Sensor (PWFS), are the current preference for high contrast imaging due to their high sensitivity. However, these wavefront sensors have intrinsic nonlinearities that constrain the range where conventional linear reconstruction methods can be used to accurately estimate the incoming wavefront aberrations. We propose to use Convolutional Neural Networks (CNNs) for the nonlinear reconstruction of the wavefront sensor measurements. It is demonstrated that a CNN can be used to accurately reconstruct the nonlinearities in both simulations and a lab implementation. We show that solely using a CNN for the reconstruction leads to suboptimal closed loop performance under simulated atmospheric turbulence. However, it is demonstrated that using a CNN to estimate the nonlinear error term on top of a linear model results in an improved effective dynamic range of a simulated adaptive optics system. The larger effective dynamic range results in a higher Strehl ratio under conditions where the nonlinear error is relevant. This will allow the current and future generation of large astronomical telescopes to work in a wider range of atmospheric conditions and therefore reduce costly downtime of such facilities.

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression.

BACKGROUND: Individuals presenting for care with severe immunosuppression typically have high plasma HIV viral load (pVL) and may transmit HIV before and after initiation of combination antiretroviral therapies (cART). PATIENTS AND METHODS: Using risk equations and data collected in the IMEA 040 DATA trial on sexual behaviour and pVL level of 84 HIV-infected patients (23 women), we estimated monthly rates of HIV transmission for each virologically unsuppressed participant (pVL >50 copies/mL) who reported sex with HIV-negative or unknown serostatus (HNUS) partners at cART initiation, 24 weeks (W24) and W48 after; rates were considered negligible for other participants. RESULTS: At cART initiation, median pVL was 5.4 log10 copies/mL. The percentage of virologically unsuppressed patients decreased, from 100% at cART initiation to 27% (95% CI 16%-43%) for heterosexuals and 8% (95% CI 2%-22%) for MSM at W48 (P < 0.001). The percentage of patients reporting sex with HNUS partners increased between cART initiation and W48, from 23% (95% CI 10%-42%) to 42% (95% CI 25%-61%) for heterosexuals (P = 0.042) and from 41% (95% CI 21%-64%) to 73% (95% CI 52%-88%) for MSM (P = 0.004). Median monthly HIV transmission rates were 0.0540 (IQR 0.0339-0.0742) for MSM and 0.0018 (IQR 0.0014-0.0191) for heterosexuals at cART initiation, and were reduced by 95% (95% CI 87%-100%) for heterosexuals and 98% (95% CI 95%-100%) for MSM as early as W24. CONCLUSIONS: Risk of onward transmission for severely immunosuppressed individuals is high before and within the first weeks of cART, and persists, at a substantially reduced level, beyond 24 weeks of cART for some individuals. Earlier cART and protecting HIV-negative partners until full viral suppression is achieved could reduce HIV transmission.

Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens.

OBJECTIVES: To compare the frequency of the selection of the M184V/I resistance mutation in HIV-infected patients who experienced virological failure while receiving emtricitabine (FTC) or lamivudine (3TC), administered with tenofovir disoproxil fumarate (TDF) and either efavirenz (EFV) or a ritonavir-boosted protease inhibitor (PI; lopinavir or atazanavir). METHODS: Patient data held at two clinical centres in France were analysed retrospectively. Eligible patients had experienced virological suppression (plasma HIV RNA <200 copies/mL) for ≥ 6 months before experiencing their first virological failure (at least two measurements of plasma HIV RNA ≥ 200 copies/mL). RESULTS: Of the 880 patients eligible for the study, 278 patients had experienced virological failure while receiving FTC + TDF + ritonavir-boosted PI, 257 while receiving FTC + TDF + EFV, 178 while receiving 3TC + TDF + EFV and 167 while receiving 3TC + TDF + ritonavir-boosted PI. Proportions of patients harbouring the M184V/I mutation were 24% (n = 62) for those who received FTC + TDF + EFV versus 51% (n = 91) for 3TC + TDF + EFV (P < 0.0001; Fisher's exact test); proportions were 11% (n = 30) for FTC + TDF + ritonavir-boosted PI versus 22% (n = 37) for 3TC + TDF + ritonavir-boosted PI (P = 0.002; Fisher's exact test). The use of lamivudine versus emtricitabine (P = 0.001), non-nucleoside reverse transcriptase inhibitors versus ritonavir-boosted PIs (P = 0.01) and the level of viral load at the time of virological failure (P = 0.01) were associated with selection of the M184V/I mutation (logistic regression analysis). CONCLUSIONS: Emtricitabine and lamivudine showed differing resistance profiles when administered in combination with tenofovir disproxil fumarate and either efavirenz or a ritonavir-boosted PI. The prevalence of the M184V/I resistance mutation was significantly lower in patients who received emtricitabine and tenofovir disoproxil fumarate than in those who received lamivudine and tenofovir disoproxil fumarate.

Gag mutations can impact virological response to dual-boosted protease inhibitor combinations in antiretroviral-naïve HIV-infected patients.

ANRS 127 was a randomized pilot trial involving naïve patients receiving two dual-boosted protease inhibitor (PI) combinations. Virological response, defined as a plasma HIV RNA level of <50 copies/ml at week 16, occurred in only 41% patients. Low baseline plasma HIV RNA level was the only significant predictor of virological response. The purpose of this study was to investigate the impact on virological response of pretherapy mutations in cleavage sites of gag, gag-pol, and the gag-pol frameshift region. The whole gag gene and protease-coding region were amplified and sequenced at baseline and at week 16 for 48 patients still on the allocated regimen at week 16. No major PI resistance-associated mutations were detected either at baseline or in the 26 patients who did not achieve virological response at week 16. Baseline cleavage site substitutions in the product of the gag open reading frame at positions 128 (p17/p24) (P = 0.04) and 449 (p1/p6(gag)) (P = 0.01) were significantly more frequent in those patients not achieving virological response. Conversely, baseline cleavage site mutation at position 437 (TFP/p6(pol)) was associated with virological response (P = 0.04). In multivariate analysis adjusted for baseline viral load, these 3 substitutions remained independently associated with virological response. We demonstrated here, in vivo, an impact of baseline polymorphic gag mutations on virological response in naïve patients receiving a combination of two protease inhibitors. However, it was not possible to link the substitutions selected under PI selective pressure with virological failure.

Simplification and first validation of a short battery of patient questionnaires for clinical management of HIV-infected patients: The HIV-SQUAD (Symptom Quality of life Adherence) Questionnaire.

PURPOSE: Questionnaires assessing patient-reported outcomes in HIV are either too long or not HIV-specific. Our aim was to develop and validate a simplified HIV patient questionnaire. METHOD: 607 HIV patients treated with a combination of antiretroviral (ARV) drugs were enrolled in an observational, longitudinal study. Questionnaires covering health-related quality of life (HRQoL), satisfaction, tolerability, and adherence were administered at baseline (BL) and Month 3 (M3). The items were selected according to their content and discriminant properties. The simplified questionnaire was then administered at Month 12 (M12). Psychometric properties of physical wellbeing, psychological well-being, and global HRQoL scores were assessed. RESULTS: The simplified questionnaire included 12 HRQoL items, 13 side-effects items, and one visual analog scale (VAS) measuring adherence. The principal component analysis (PCA) confirmed the validity of the global HRQoL score. The multivariate analysis showed acceptable-to-good internal consistency of the three scores. Convergent and discriminant validity were excellent for the physical score. The global score showed significant differences according to time since diagnosis, hepatitis coinfection, CD4 count, and viral load. CONCLUSION: This questionnaire deals with the major aspects of HIV patient perceptions. The global HRQoL score is well correlated to the surrogate markers of HIV. Such a questionnaire may represent a new tool for the therapeutic management of HIV-infected patients. Further steps are required to complete these results.

Quality of life and depression among HIV-infected patients receiving efavirenz- or protease inhibitor-based therapy in Senegal.

BACKGROUND: Efavirenz has been associated with neuropsychiatric disorders, but little is known about depression and quality of life in sub-Saharan Africa, where nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are still the first-line treatment recommended by the World Heath Organization (WHO) and are widely prescribed. METHODS: In a cross-sectional study, we evaluated quality of life and depression among Senegalese patients receiving efavirenz- or protease inhibitor (PI)-based regimens. Two hundred consecutive patients who had been taking highly active antiretroviral therapy (HAART) for more than 6 months were asked to complete a questionnaire. RESULTS: According to the Center for Epidemiologic Studies Depression Scale (CES-D), 18% had depression (19% for patients on a PI-based regimen and 17% for patients on efavirenz-based treatment). Fifty-nine per cent of the patients reported no health problems in the past 4 weeks. A quarter of patients had sleep disorders. Moderate or slight adverse events were reported by 28.5% of patients. CONCLUSIONS: Quality of life and depression scores remained good in both study groups. However, quality of life and depression should be monitored in follow-up of HIV-infected patients in sub-Saharan Africa.

Comparison of gastrointestinal tolerability and patient preference for treatment with the 625 mg and 250 mg nelfinavir tablet formulations.

OBJECTIVES: To compare gastrointestinal (GI) tolerability and patient preference for the new 625 mg formulation of nelfinavir (NFV) and the marketed 250 mg tablets (Viracept) in HIV-1-infected patients. METHODS: Virologically controlled patients (n=126) treated with a nelfinavir (NFV) 250 mg-containing regimen for > or =8 weeks completed a stool diary for 14 days to assess baseline bowel function. After switching to the NFV 625 mg formulation [1250 mg twice a day (bid)] for 28 days, patients continued their stool diaries and at study completion answered a questionnaire regarding formulation preferences. RESULTS: The incidence and mean weekly duration of GI upset over a 2-week period were lower with NFV 625 mg than with NFV 250 mg (79.8% vs. 84.9% of patients and 2.1 vs. 3.0 days, respectively). Fewer patients experienced moderate or severe diarrhoea with NFV 625 mg (6.5% vs. 11.1%), and the incidence of investigator-assessed diarrhoea also decreased with NFV 625 mg. Importantly, there was a significant improvement overall in the incidence of diarrhoea (any grade) when patients switched to NFV 625 mg [38 of 124 (31%) improving, 69 of 124 (56%) stable and 17 of 124 (14%) worsening on NFV 625 mg; P<0.01]. At study completion, most patients expressed a preference to continue treatment with NFV 625 mg [112 of 122 (91.8%); P<0.0001], with only one patient (0.8%) preferring to resume treatment with NFV 250 mg. The new formulation was well tolerated with no new safety concerns. CONCLUSIONS: The new NFV 625 mg formulation is better tolerated and preferred by patients switching from NFV 250 mg tablets. By reducing the daily pill count and improving GI tolerability, the NFV 625 mg formulation may enhance patient adherence to NFV-containing antiretroviral regimens and thus potentially improve virological outcomes.

Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study.

BACKGROUND: To assess the efficacy and safety of the triple NRTI combination of abacavir (ABC), lamivudine (3TC), and tenofovir (TDF) in a once-daily regimen. METHOD: 38 HIV-naive patients (pts) were treated in a prospective open-arm study over 48 weeks (W48). Virological failure was defined as never achieving plasma HIV-1 RNA < 400 copies/mL or rebound of > or = 0.7 log10. RESULTS: 12/36 (33%) pts had virologic failure at W24 and 10 additional pts had HIV RNA > 50 copies/mL at W12 or W24. There was a significant association between baseline viral load (VL) and virologic failure in 0%, 29%, and 64% pts with baseline VL levels < 4, 4-5, and > 5 log10 copies/mL, respectively (p = .014). 76% of pts developed K65R and M184V/I mutations by W24, and 19% developed M184V/I alone. At W4, 86% of pts had adequate plasma Cmin for the 3 drugs. 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome (< 50 copies/mL; median follow-up 48 weeks). CONCLUSION: Convergent genetic pathway to resistance, in conjunction with lower antiretroviral potency, may explain the high rate of selection K65R and M184V mutations. These mutations did not appear to have a negative effect on rescue therapy with a variety of regimens.

Comparison of 1-micro g and 250-micro g corticotropin stimulation tests for the evaluation of adrenal function in patients with acquired immunodeficiency syndrome.

Many patients with acquired immunodeficiency syndrome (AIDS) have symptoms suggestive of adrenal insufficiency, but a normal 250- micro g corticotropin (ACTH) stimulation test. We compared the results of 1- micro g and standard 250- micro g ACTH stimulation tests in patients with AIDS. Each patient was studied on 2 separate days. On day 1, 1 micro g ACTH was given intravenously at 8 am after an overnight fast and serum cortisol levels were measured at baseline, and 30 and 60 minutes after ACTH infusion. On day 2, the procedure was repeated with 250- micro g ACTH. An absolute peak cortisol value of > 18 micro g/dL and an increment of 7 micro g/dL or more from baseline constituted a normal response. Among 31 patients, 16 (52%) had discrepant results: 14 (45%) had subnormal responses to 1 micro g ACTH but normal responses to 250 micro g ACTH (group 1); 2 (6%) had normal responses to 1 micro g but subnormal responses to 250 micro g (group 2) ACTH; 6 patients (19%) had concordant abnormal responses (group 3); and 9 (30%) had concordant normal responses (group 4). Eight patients of group 1 underwent a confirmatory insulin tolerance test (ITT); 4 of these patients had abnormal responses to ITT. Kappa statistic and McNemar's test were used to evaluate the data. A kappa statistic value of 0.095 and a P value less than.003 for the McNemar test indicate only random level of agreement and significant differences in the probability of positive result between the 2 ACTH tests. We conclude that discrepancies between the 1- micro g and the 250- micro g ACTH stimulation tests are common in patients with AIDS, with the likelihood of agreement with the "gold standard" ITT of only 50% for each test in our sample of patients. Larger studies are needed to further evaluate the use of these tests in patients with AIDS.

Pituitary lymphoma presenting as fever of unknown origin.

An 86-yr-old woman presented with fever of unknown origin. When laboratory evaluation revealed partial hypopituitarism, a magnetic resonance imaging scan of the head was performed and revealed a sellar mass consistent with a pituitary adenoma. Only after other possible etiologies for fever were excluded did she undergo transsphenoidal resection of the sellar mass, which proved to be a B-cell lymphoma. Primary central nervous system lymphoma of the pituitary region is a rare cause of a sellar mass, and this is the first reported case of pituitary lymphoma whose presenting manifestation was fever of unknown origin. Several disease processes can manifest themselves as fever and a sellar mass, including lymphomas. In our case, only surgical biopsy could make a diagnosis and distinguish this process from the more common pituitary adenoma.

Gender and age in the biochemical assessment of cure of acromegaly.

The principal biochemical criteria for cure in acromegaly are normalization of both glucose-suppressed GH levels and IGF-I levels. As we have reported previously, measurement of GH by highly sensitive assay in conjunction with IGF-I levels has led to a re-appraisal of "normal" GH suppression criteria during an OGTT in subjects with acromegaly. In some patients with active acromegaly, glucose-suppressed GH levels as measured by highly sensitive assay are much lower than could previously be appreciated with less sensitive GH assays and some other patients in apparent remission have subtle abnormalities of GH suppression. A question to arise is whether gender differences in glucose-suppressed GH levels as found by others in young healthy subjects should be considered in our interpretation of OGTT criteria for cure in acromegaly. Therefore, we have evaluated parameters of GH secretion in a larger number of subjects from our cohort of postoperative patients with acromegaly and in healthy subjects in order to determine if gender or age associated differences in these parameters exist. Ninety-two subjects with acromegaly (49 men, 43 women) and 46 age-matched healthy subjects (26 men, 20 women) were evaluated with baseline GH and IGF-I levels and nadir GH levels after a 100 g. OGTT. GH was assayed by highly sensitive IRMA (DSL). Basal GH levels were higher in female than in male healthy subjects, but the fall in GH from baseline (% suppression) was also greater in females resulting in no significant difference in mean nadir GH levels in female vs. male healthy subjects (0.09 vs. 0.08 microg/L). In the subjects with acromegaly, there were no significant gender differences in basal, %GH suppression or nadir GH levels. Basal and nadir GH levels correlated significantly only in subjects with active disease (r=0.84, p<.0001). Similarly, IGF-I levels correlated significantly with basal (r=0.573, p=.0012), and nadir (r=.702, p<.0001) GH levels only in subjects with active disease. Gender differences in IGF-I levels were not apparent in any group of subjects. As expected, IGF-I levels declined with age in those groups of subjects with normal IGF-I levels. Nadir GH levels did not vary with age. In conclusion, we have not found significant gender or age-related differences in nadir GH levels and thus our data does not support separate OGTT criteria for cure in men and women with acromegaly.

Frequency of cytokine-producing T cells in HIV-infected patients treated with stavudine, didanosine, and ritonavir.

To assess prospectively the influence of the control of viral replication on the frequency of cytokine-producing T cells, and to correlate these changes with immune activation, we conducted a 15-month follow-up study of IFN-gamma- and IL-2-producing CD4+ and CD8+ T cells at a single-cell level in 12 previously untreated patients receiving highly active antiretroviral therapy (HAART). At baseline we observed a strikingly high proportion of IFN-gamma-producing CD8+ T cells. The treatment-induced decrease in the proportion of IFN-gamma-producing CD8+ T cells ran parallel to the decrease in HLA-DR+ and CD38+CD8+ T cell subsets and was associated with the reduction in HIV RNA level. IL-2-producing cells were mainly CD4+. As a consequence of CD4+ T cell loss, the number of IL-2-producing CD4+ T cells was lower in patients than in control subjects (52 vs. 171 cells/microl), but the proportion of these cells was unchanged (22.4 vs. 19.3). During therapy the proportion of CD4+ IL-2-producing cells was initially stable and then fell markedly at month 5, followed by a gradual return to previous values. The reduction in viral load was associated with the fall in the proportion of CD4+ activated subsets. Intracellular cytokine assays are a new approach to the assessment of T cell function in HIV infection. Our results suggest that the functional capacity of CD4+ T cells is probably less severely altered than previously thought on the basis of conventional assays. CD8+ T cells exhibit an increased capacity to produce IFN-gamma that is associated with an increase in activation marker expression. These alterations decrease partially and in parallel under treatment.

The role of primary visual cortex (V1) in visual awareness.

In the search for the neural correlate of visual awareness, much controversy exists about the role of primary visual cortex. Here, the neurophysiological data from V1 recordings in awake monkeys are examined in light of two general classes of models of visual awareness. In the first model type, visual awareness is seen as being mediated either by a particular set of areas or pathways, or alternatively by a specific set of neurons. In these models, the role of V1 seems rather limited, as the mere activity of V1 cells seems insufficient to mediate awareness. In the second model type, awareness is hypothesized to be mediated by a global mechanism, i.e. a specific kind of activity not linked to a particular area or cell type. Two separate versions of global models are discussed, synchronous oscillations and spike rate modulations. It is shown that V1 synchrony does not reflect perception but rather the horizontal connections between neurons, indicating that V1 synchrony cannot be a direct neural correlate of conscious percepts. However, the rate of spike discharges of V1 neurons is strongly modulated by perceptual context, and these modulations correlate very well with aspects of perceptual organization, visual awareness, and attention. If these modulations serve as a neural correlate of visual awareness, then V1 contributes to that neural correlate. Whether V1 plays a role in the neural correlate of visual awareness thus strongly depends on the way visual awareness is hypothesized to be implemented in the brain.

Variability of attitudes toward early initiation of HAART for HIV infection: a study of French prescribing physicians.

This study assessed prescribing physicians' attitudes toward early initiation of HAART, three months after the dissemination of the first French official treatment guideline. Telephone interviews have been made in a national random sample of physicians with full- or part-time practice in hospital departments delivering care for HIV-infected patients. Questionnaires included hypothetical clinical cases. Logistic regression compared characteristics of respondents according to attitudes toward HAART. Among the 483 respondents (response rate = 87.0%), agreement was high with official recommendations to systematically initiate HAART with protease inhibitors (PIs) for patients with CD4+ cell counts < or = 300/mm3, following a diagnosis of acute primary HIV infection, or for HIV sexual risk post-exposure prophylaxis. Confronted with a case of a naive asymptomatic patient with stable 450 CD4+/mm3, 34.6% would prescribe HAART with PIs in any case, and 29.8% only if the patient has plasma viral load < or = 10,000 HIV RNA copies/ml. The remaining 35.6% would not prescribe PIs and were older, had limited activity in HIV care and expressed more interest in alternative medicines. To avoid a confusing impact of variability of clinical attitudes toward uncertainties associated with antiretroviral treatments among HIV-infected patients, shared decision-making between patient and physician should be promoted for initiation of HAART.

[Therapeutic attitude to HIV infection: uncertain and variable scientific attitudes. 1998 national survey of physicians prescribing antiretroviral drugs]. / Attitudes thérapeutiques pour l'infection à VIH: incertitudes scientifiques et variabilités. Enquête nationale 1998 auprès des médecins prescripteurs d'antirétroviraux. Groupe PAMPA. Pratiques et Attitudes des Médecins Prescriteurs d'Antirétroviraux.

OBJECTIVES: Analyze the attitudes of French practitioners managing HIV infected patients towards multidrug antiretroviral therapies with protease inhibitors, open issues, and the official guidelines (Dormont report). METHODS: A telephone survey was conducted in February-March 1998 on a random sample of the nation file of hospital physicians prescribing antiretroviral drugs (response rate 87%, n = 483). RESULTS: The responding clinicians were in general agreement on defining virological efficacy at three months treatment as an undetectable viral load (86.5%). There was a general concensus on multidrug therapy with a protease inhibitor in case of primary infection (83.2%) or sexual exposure with risk of HIV transmission (83.2%). Inversely, only 43.7% abandoned PCP and toxoplasmosis prophylaxis in patients with CD4 counts above 350/mm3 taking tritherapy antiretroviral regimens. When asked to state their approach to a hypothetical case of an asymptomatic patient with a CD4 count of 450, 35.6% would not propose multidrug therapy with an antiprotease, 29.8% would only envisage such a regimen if the viral load was above 10,000 copies/ml, and finally 34.6% would prescribe a multidrug regimen with a protease inhibitor whatever the viral load. CONCLUSION: The variability observed in routine clinical practices would appear to be justified in light of the uncertainty about the long-term effects of the new antiretroviral drugs for HIV/AIDS.

Changes in blood CD8+ lymphocyte activation status and plasma HIV RNA levels during antiretroviral therapy.

OBJECTIVE: To analyse the relationship between CD8+ lymphocyte phenotype alterations and plasma HIV RNA levels in HIV-infected patients treated with the zidovudine-didanosine combination. METHODS: A total of 30 HIV-infected patients who had never received antiretroviral therapy and who were starting treatment with a combination of zidovudine and didanosine were prospectively studied. Multiparameter flow cytometric analysis of CD8+ lymphocytes and plasma HIV RNA determination were performed on day 0, day 15 and monthly from months 1 to 6. RESULTS: Patients were divided into three categories according to the time-course of plasma HIV RNA levels. In 14 patients, an early and sustained fall in plasma HIV RNA to below the detection limit (500 copies/ml) was observed; in 10 patients, the fall was transient; in six patients, plasma HIV RNA was always detectable (non-responders). The mean CD4+ lymphocyte gain was 120 x 10(6)/l at month 6 in sustained and transient responders, and 55 x 10(6)/l in non-responders. A significant fall in the proportion of CD8+ lymphocytes with an activated phenotype was observed only in the two groups of responders, and was higher in the sustained responders (CD38+HLA-DR+, -56.8%; CD38+CD45RO+, -54.0%; HLA-DR+CD45RO+, -48.4%; CD38+CD28-, -47.3%). CONCLUSION: A fall in the proportion of activated CD8+ lymphocytes is associated with the disappearance of HIV RNA from plasma during antiretroviral therapy. Undetectable plasma HIV RNA is not associated with a return to normal CD8+ lymphocyte activation status after 6 months of treatment, suggesting that viral replication persists in lymphoid tissues.

Making sex safer for people with learning disabilities.

The author argues that HIV prevention work should be targeted, not according to outdated and prejudiced notions of 'high-risk' groups, but according to an analysis of those affected by a number of identifiable risk factors. These factors occur within populations that are marginalised and socially devalued. Similarities are drawn between the perceived sexualities of two of these population groups: gay men and people with learning disabilities. The construction of these sexualities, it is argued, pose a direct threat to people with learning disabilities. The implications for services are highlighted, and action urged in the key areas of staff training, sex education, sexual health service accessibility and equal opportunities. The article concludes by suggesting that people with learning disabilities are at risk of HIV infection precisely because it is perceived that they are not.