2020

19th February Ryom et al., Use of contemporary protease inhibitors and risk of incident chronic Kidney disease in persons with HIV


Use of contemporary protease inhibitors and risk of incident chronic Kidney disease in persons with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study.   Journal of Infectious Diseases

Ryom et al. on behalf of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study aimed to assess whether cumulative use of more contemporary protease inhibitors (PIs), including ritonavir-boosted darunavir (DRV/r) and ritonavir-boosted atazanavir (ATV/r), are associated with an increased incidence of chronic kidney disease (CKD) to a similar extent as some of the older PIs.

The incidence of CKD (10.0/1000 person-years of follow-up; 95% confidence interval, 9.5–10.4/1000 person-years of follow-up) increased gradually with increasing exposure to ATV/r, but the relation was less clear for DRV/r. After adjustment, only exposure to ATV/r (adjusted incidence rate ratio, 1.4; 95% confidence interval, 1.2–1.6), but not exposure to DRV/r (1.0; .8–1.3), remained significantly associated with CKD.

In conclusion, in this large heterogeneous cohort of people living with HIV, more extended use of DRV/r was not significantly associated with a gradually increasing incidence of CKD, even after a median follow-up of >6 years. Discontinuation of DRV/r use was, in contrast to discontinuation of ATV/r, unrelated to declining eGFRs. A gradually increasing CKD risk with longer use of ATV/r was confirmed, with a 40% increased CKD incidence after 4 years of use, when compared with those never exposed to ATV/r.

pdf publication

11th February Rodger et al., HIV transmission through condomless sex in serodifferent gay couples


Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.   Lancet

The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. In the first phase of the PARTNER study, some evidence on transmission risk in gay men was provided but follow-up in these studies was not sufficient to exclude a significant upper limit of risk around the study estimates of zero transmissions in gay men. In PARTNER2, Rodger et al. on behalf of the PARTNER study group aimed to fill this gap and to produce a similar level of evidence for transmission risk through condomless anal sex between men with suppressive ART (defined as HIV-1 RNA viral load <200 copies per mL) to that generated for heterosexual couples in PARTNER1.

Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1’593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76’088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up).

In conclusion, the results from the PARTNER studies support wider dissemination of the message of the U=U campaign (undetectable equals untransmittable) that risk of transmission of HIV in the context of virally suppressive ART is zero. This dissemination is necessary to promote the benefits of early testing and treatment and to tackle stigma, discrimination, and criminalization laws that continue to affect HIV-positive people. However, U=U is only easy to apply when HIV-positive people have access to testing, effective treatment, viral load monitoring to levels of less than 200 copies per mL, and support to reach and maintain viral suppression.

pdf publication

4th February Neesgaard et al., Uptake and effectiveness of 2DR versus 3DR


Uptake and effectiveness of two-drug compared with three-drug antiretroviral regimens among HIV-positive individuals in Europe.    AIDS

Neesgaard et al. on behalf of the EuroSIDA study analysed the uptake of two-drug antiretroviral regimens (2DRs), factors associated with starting or switching to a 2DR in the European-based EuroSIDA cohort, and virologic and immunologic outcomes of using 2DRs compared with three-drug regimens (3DRs) in this large, heterogeneous, population of people living with HIV (PLWHIV) seen in routine clinical care.

Virologic outcomes were assessed on-treatment as the proportion of individuals with controlled viral load (<400 copies/ml), or with a composite modified FDA snapshot endpoint (mFDA), with mFDA success defined as controlled viral load at 6 months or 12 months for individuals with a known viral load, no regimen changes, AIDS or death. Immunologic response was defined as a 100 cells/[mu]l or a 25% increase in CD4+ cell counts from baseline.

Between 1 July 2010 and 31 December 2016, 423 individuals started or switched to a 2DR (eight antiretroviral-naive) and 4’347 started a 3DR (566 naive). Individuals on 2DR tended to have suppressed viral load, higher CD4+ cell counts and more comorbidities at baseline compared with those on 3DR. There were no differences in the proportions of individuals who obtained on-treatment or mFDA success, and no significant differences in the adjusted odds ratios for mFDA success or immunologic responses between the 2DR and 3DR groups at 6 months or 12 months.

In conclusion, the study found that the 2DRs in this analysis were largely used according to the current clinical guidelines. The study-results show that 2DRs in the period were mainly prescribed to antiretroviral-experienced individuals who switched from their previous regimen with virologic suppression, high CD4+ cell counts and preexisting or higher risk of comorbidities. Although the study observed favourable outcomes for antiretroviral-naive individuals starting a 2DR, the numbers were too low to allow meaningful conclusions. Overall, virologic and immunologic outcomes in individuals on 2DRs were similar to individuals on 3DRs in this selected population, in line with results from randomized clinical trials, although confounding by indication cannot be fully excluded.

PubMed

30th January Metral et al., Screening questions for neurocognitive impairment


How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?    HIV Medicine

Metral et al. for the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study group from the Swiss HIV Cohort Study aimed to determine the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying neurocognitive impairment (NCI).

Patients aged ≥45 years were enrolled between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria.

Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001).

In conclusion, in this large cohort of patients with well-controlled HIV infection, one quarter had cognitive complaints, most frequently related to memory loss. The EACS screening questions had an NPV of 0.7 for excluding HIV-associated NCI in NAMACO study participants using Frascati criteria. However, it remains to be seen whether the PPV and NPV of these questions improve if patients are classified according to other, yet to be defined, NCI severity criteria. Currently, these questions lack sensitivity and specificity as a tool to guide clinicians as to which patients should be referred for formal neuropsychological testing.

pdf publication

23rd January Borges et al., SMART and START combined analysis


The effect of interrupted/deferred antiretroviral therapy on disease risk: A SMART and START combined analysis.    Journal of Infectious Disease

Borges et al. on behalf of the Strategies for Management of Antiretroviral Therapy (SMART) and Strategic Timing of AntiRetroviral Treatment (START) studies aimed to quantify the relative difference between deferred/intermittent antiretroviral therapy (ART) and immediate/continuous ART on risk of AIDS- and non-AIDS–defining events. Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death.

Among 10’156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32– 2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.

In conclusion, compared to a strategy of immediate/continuous ART, a strategy of deferred/intermittent ART, increased the risk of AIDS and SNA events among HIV-positive persons consistently in SMART and START. Interventions in SMART and START led to similar absolute differences in mean CD4+ cell count and percentage with viral suppression, which in turn led to similar relative risk estimates for AIDS and SNA in each study. Pooled treatment differences for the composite outcome of AIDS, SNA, or death were similar across a number of subgroups.

pdf publication

16th January Hampel et al., Chemsex drugs in the Swiss HIV Cohort Study


Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017.    HIV Medicine

Hampel et al. aimed to analyse the trend in the consumption of all recreational drugs over the last 11 years among all participants in the Swiss HIV Cohort Study (SHCS), with a particular focus on the use of chemsex drugs and other potentially sex-enhancing drugs among men who have sex with men (MSM).

Drugs referred to as chemsex drugs included N-methylamphetamine (methamphetamine), 4-methylmethcathinone (mephedrone), c-hydroxybutyric acid/c-butyrolactone (GHB/GBL) and ketamine. Drugs referred to as sex-enhancing drugs included cocaine, 3,4-methylenedioxymethamphetamine (XTC/MDMA), amyl nitrite and amphetamine.

The study analysed 166’167 follow-up entries for 12’527 SHCS participants, including 7’101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, there was a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P <0.001) and GHB/GBL (from 1.0 to 3.4%; P <0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with non-steady partners, and higher prevalences of depression, syphilis and hepatitis C.

In conclusion, the study identified a significant increase in the use of chemsex drugs, in particular methamphetamine and GHB/GBL, among MSM diagnosed with HIV infection in Switzerland and a strong association of this use with coinfections and depression. In light of these findings, more studies in this field are needed to better understand the relationship between sexual behaviour, drug consumption and depression in order to inform successful harm reduction strategies. This further understanding will not only help the patients and potentially decrease numbers of other sexually transmitted infections, including viral hepatitis C, but will also be crucial to the understanding of the current drivers in the ongoing HIV epidemic.

pdf publication

9th January Christe et al., Imaging PJP in HIV-pos and renal transplant patients


Imaging patterns of Pneumocystis jirovecii pneumonia in HIV-positive and renal transplant patients - a multicentre study.    Swiss Medical Weekly

Christe et al. aimed to explore the computed tomography (CT) and chest X-ray (CXRs) imaging features of Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients from two well-defined cohorts, the Swiss HIV Cohort Study (SHCS) and renal transplant recipients (RTRs) included in the Swiss Transplant Cohort Study (STCS).

From 2005 to 2012, 84 patients with PJP (RTR n = 24; HIV n = 60) were included in this retrospective multicentre study. CT scans and CXRs were recorded within 2 weeks after the onset of symptoms. PJP diagnosis was confirmed either by cytology/histology or successful empirical treatment. Two blinded radiologists analysed the conventional chest films and CT images.

Consolidations and solid nodules prevailed on CT in RTRs (91.7 ± 5.6% vs 58.3 ± 6.4% with HIV, p = 0.019 and 91.7 ± 5.6% vs 51.6 ± 6.5% with HIV, p = 0.005). HIV-positive patients with PJP showed more atelectasis (41.7 ± 6.4% vs 4.2 ± 4.1% in RTRs, p = 0.017) and hilar lymph node enlargement (23.3 ± 5.5% vs 0.0 ± 0.0% in RTRs, p = 0.088). Ground glass opacification was found in all cases. Pneumothorax was a rare complication, occurring in 3% of the HIV-positive patients; no pneumothorax was found in the RTRs. On CXR, the basal lungs were more affected in HIV-positive patients as compared with RTRs (p = 0.024).

In conclusion, the PJP radiological CT findings in renal transplant patients were dominated by multifocal consolidation and solid nodularities, whereas in the HIV population more classic subpleural sparing was present. A common feature in both groups was ground glass opacification. Of note, pulmonary cysts, previously described as a hallmark feature in PJP, were present in only 4% of the HIV-positive patients and in none of the RTRs. With the advance of prophylaxis in high-risk groups, this classic complication is now an infrequent finding. Based on the differing imaging manifestations of PJP in transplant recipients and HIV-positive patients, it is of utmost importance for radiologists to be aware of the spectrum of patterns in the context of different underlying diseases and to show high awareness in high-risk groups.

pdf publication