Post-exposure prophylaxis completion and condom use in the context of potential sexual exposure to HIV.

OBJECTIVES: Post-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours. METHODS: A retrospective analysis was carried out on data from the French Dat'AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant). RESULTS: Overall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner's HIV status. CONCLUSIONS: We provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.

Reevaluation of possible outcomes of infections with human immunodeficiency virus.

Several lines of evidence indicate that HIV infection can result in several possible incomes, including a very small proportion of individuals whose HIV replication is controlled after treatment interruption (known as HIV posttreatment controllers) or spontaneously without any treatment (known as HIV elite controllers). Both types of individuals are HIV RNA negative but HIV DNA positive, with living virus which can be stimulated ex vivo. A review was conducted to assess the literature on yet rarer cases with detectable integrated HIV DNA without HIV infectious virus in HIV-seropositive or -negative individuals. Three categories of patients were identified: (a) HIV-seropositive individuals with apparent spontaneous cure from their HIV infection, (b) HIV-seronegative children born to HIV-infected mothers and (c) highly exposed seronegative adults. Validity criteria were proposed to assess the presence of integrated HIV DNA as possible or unquestionable in these three categories. Only three articles among the 22 ultimately selected fulfilled these criteria. Among the highly exposed seronegative subjects, some individuals were described as being without integrated HIV DNA, probably because these subjects were not investigated using relevant, highly sensitive methods. Finally, we propose a definition of spontaneous cure of HIV infection based on clinical, immunologic and virologic criteria.

HIV infection en route to endogenization: two cases.

The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3-100% per gene) and 24% overall (0-50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication.

Preexposure prophylaxis (PrEP) of HIV infection in France: a nationwide cross-sectional study (PREVIC study).

Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.

Severe weight loss in HIV / HCV-coinfected patients treated with interferon plus ribavirin: incidence and risk factors.

Weight loss is reported by more than 20% of hepatitis C virus (HCV)-monoinfected patients treated with the peg-interferon (peg-IFN) and ribavirin combination. The aim of this study was to determine the incidence and risk factors of severe weight loss (> or =10%) in human immunodeficiency virus (HIV) / HCV-coinfected patients participating in a randomized, controlled 48-week trial comparing peg-IFN alpha 2b plus ribavirin with IFN alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, anti-HCV therapy and clinical and laboratory findings. One hundred eleven (28.9%) of 383 patients who received at least one dose of anti-HCV treatment subsequently had severe weight loss. Among patients who took at least 80% of the planned total dose, severe weight loss occurred in 74 patients (32.7%). In multivariate analysis, age >40 years [hazard ratio (HR), 1.59; 95% CI 1.09 to 2.31; P = 0.016], body mass index (BMI) >22 (HR, 1.72; 95% CI, 1.16 to 2.55; P = 0.0069), peg-IFN alpha-2b (HR, 1.82; 95% CI, 1.24 to 2.69; P = 0.0022) and female sex (HR, 1.60; 95% CI, 1.05 to 2.43; P = 0.027) were associated with severe weight loss. In contrast, patients taking non-nucleoside reverse transcriptase inhibitors (NNRTI)-containing antiretroviral regimens were less likely to lose weight (HR, 0.62; 95% CI, 0.39 to 0.96; P = 0.034). Lipodystrophy tended to occur more frequently in patients who had severe weight loss than in the other patients (26.1%vs 17.6%; P = 0.0682) and patients whose weight loss >5% persisted 24 weeks after the completion of anti-HCV therapy (n = 58 / 111) were more likely to be receiving stavudine-based antiretroviral therapy, suggesting that mitochondrial toxicity plays some role in weight loss. These findings show that severe weight loss is a frequent side effect of anti-HCV therapy in HIV / HCV-coinfected patients. The underlying mechanisms remain to be identified.

[Liposomal amphotericin B in secondary prophylaxis of visceral leishmaniasis in HIV-infected patients: report of five clinical cases]. / L'amphotéricine B liposomale en prophylaxie secondaire chez les patients VIH+ atteints de leishmaniose viscérale: à propos de cinq cas.

Treatment of visceral leishmaniasis in HIV patients encounters inefficacy and relapse due to drug resistance, toxicity and immunodepression. Our goal was to evaluate treatment of these patients by liposomal amphotericin B (L-AmB). Since 1998, five clinical files were exploitable out of 13 patients. Protocols used bolus doses ranging between 2.9 and 4.1 mg/kg dispatched on 5-24 days, followed by maintenance dose ranging from 2.7 to 3.8 mg/kg every 15 days. Attack treatment involved high bolus dose (cumulated doses ranging from 60 to 86 mg/kg at day 30) and allowed favorable clinical and biological results with healing in four patients. Secondary prophylaxis with L-AmB has been efficacious and well tolerated in three patients. Although literature and study results cannot indicate a standard therapeutic care in these patients, an initial treatment by L-AmB at doses higher than marketing-approved doses with a secondary prophylaxis by L-AmB associated with an antiretroviral treatment seem to be major asset in order to obtain healing. Expanding this study to a multicenter trial should allow to better define the frequency and duration of the secondary prophylaxis and to evaluate the risk of therapeutic escape as well as the life-span increase.

[Neurospychiatric symptoms in HIV infected patients and the role of efavirenz]. / Troubles neuropsychiatriques chez les patients infectés par le VIH et rôle de l'efavirenz.

Efavirenz has now become commonly used to treat HIV infection. Neuropsychiatric disorders have been reported in patients treated with efavirenz. Several factors often make it hard to determine the cause of these disorders: HIV infected patients take many different drugs, they may suffer from various organ diseases, and may also be heavily affected by problems in their everyday life. The French experts group working on neuropsychiatric side effects of efavirenz has undertaken a review of these disorders with the aim to identify: (1) semiology, (2) epidemiology in the global population, in HIV infected patients, and in patients treated with efavirenz. The expert group suggests recommendations to manage these disorders.

TT virus infection: prevalence of elevated viraemia and arguments for the immune control of viral load.

BACKGROUND: The most recent polymerase chain reaction (PCR) detection protocols for the TT virus (TTV) permit one to identify the presence of viral DNA in the serum of a majority of healthy individuals, in the absence of any particular risk factor. This is in contrast with previous epidemiological studies that reported a higher prevalence of TTV infection in populations such as haemodialysis patients (HD), haemophiliacs, intravenous drug users or diabetics. OBJECTIVES: To show that these discrepant results were due to the different sensitivity (number of viral copies detected) of the detection protocols used in initial and more recent epidemiological studies. STUDY DESIGN AND RESULTS: We designed a standardised primary PCR assay that detects only viraemia >5x10(3) to 5x10(4) copies/ml for genotypes 1, 2 and 3, and compared the results of this test with those of a nested PCR assay which is 100-fold more sensitive. Viraemia >5x10(3) to 5x10(4) copies/ml were statistically more frequent in HD patients (54.3%), diabetics (54.7%), and HIV-infected patients with CD4 cells <200/mm(3) (69%) than in blood donors (37%) or HIV-infected patients with CD4 cells >500/mm(3) (33%). CONCLUSIONS: These data suggest a possible relationship between the prevalence of elevated viral loads and the level of immunocompetence of the populations studied, and therefore that of an immune control of TTV viraemia. This corroborates previous findings showing that the stimulation of the immune system by an interferon treatment was able to clear TTV viraemia.

[Multiple and bilateral nodular opacities revealing primary pulmonary lymphoma of the Burkitt-like type in AIDS]. / Opacités nodulaires multiples et bilatérales révélatrices d'un lymphome pulmonaire primitif de type Burkitt-like au cours du SIDA.

We report the observation of AIDS patient with a history of cough, dyspnea, fever, cachexia and bilateral nodular opacities at the chest X-ray. Infectious etiologies were initially suspected but the recovery was not obtained with their treatment. Only lung biopsy established the precise diagnosis of primary pulmonary Burkitt's-like lymphoma (BBL). The sole extranodal site of BBL at the lungs is an unusual finding. Generally, this lymphomatous proliferation is observed at the early period of the HIV infection. Immunodepression and Epstein-Barr virus (EBV) infection are the major pathogenic basis for BL as indicated by the high prevalence of EBV genomes found in malignant cells. The lack of EBV sequences in a significant proportion of Burkitt's lymphoma or BBL and AIDS-associated non-Hodgkin malignant lymphoma suggest that alternative pathogenic mechanisms may be involved. This observation permit to show the difficulties observed before the multiple and bilateral opacities whom the etiologies are varied. The prognosis of AIDS-associated BLL is very severe.

Absent inhibition of hepatitis B virus replication by azidothymidine in patients chronically coinfected by HIV-1 and HBV.

The effect of Azidothymidine (AZT) in vivo on the replication of the Hepatitis B Virus (HBV) was studied in a population of 25 patients chronically coinfected by HBV and Human Immunodeficiency Virus Type 1 (HIV-1), and receiving AZT at the usual dosage. The drug effect was evaluated by sequential measurement of the HBV DNA level. No significant activity at short and medium term was found on HBV replication in either homosexuals or IV drug users chronically coinfected by HIV-1 and HBV.