Human Immunodeficiency Virus Type 1 p24 Concentration Measured by Boosted ELISA of Heat-Denatured Plasma Correlates with Decline in CD4 Cells, Progression to AIDS, and Survival: Comparison with Viral RNA Measurement

Human immunodeficiency virus type 1 (HIV-1) RNA and p24 antigen concentrations were determined in plasma samples from 169 chronically infected patients (median CD4 cell count, 140 cells/μL; range, 0-1500 cells/μL). p24 quantification involved heat-mediated immune complex dissociation and tyramide signal amplification—boosted ELISA, which has a diagnostic sensitivity similar to that of RNA quantification by a commercial polymerase chain reaction kit. In Cox's proportional hazard models adjusted for CD4 cell count, both RNA (P < .005) and p24 (P = .043) levels were significant predictors of progression to AIDS. Measurement of p24 was superior to measurement of RNA in the model for survival (P = .032 vs. P = .19). p24 level was a significant predictor of CD4 cell decline in models adjusted for CD4 cell counts and was superior or equivalent to RNA level, depending on the group analyzed. Stratification by CD4 cell counts at baseline showed that the superiority of p24 measurement was more pronounced at lower levels of CD4 cells (<200/μL). p24 level may be of interest as a simple and inexpensive predictive marker of disease progressio

Low Incidence of Community-Acquired Pneumonia among Human Immunodeficiency Virus-Infected Patients after Interruption of Pneumocystis carinii Pneumonia Prophylaxis

We compared the incidence of bacterial pneumonia among 336 patients who discontinued trimethoprim-sulfamethoxazole (TMP-SMX) as prophylaxis against Pneumocystis carinii pneumonia (PCP) with that among 75 patients who fulfilled the criteria for discontinuation but continued receiving prophylaxis. The difference in the overall incidence rates for the 2 groups (1.2 events per 100 person-years) was not statistically significant. Discontinuation of TMP-SMX prophylaxis against PCP is not associated with a significant increase in the incidence of bacterial pneumonia among patients with a sustained CD4 cell count increase to >200 cells/μ

Association of Noncirrhotic Portal Hypertension in HIV-Infected Persons and Antiretroviral Therapy with Didanosine: A Nested Case-Control Study

Background. Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine. Methods. We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH. Matching criteria were similar duration of HIV infection, absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis in the respective case. Results. All 15 case patients had endoscopically documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died because of hepatic complications. At NCPH diagnosis, case patients and control subjects were similar concerning sex; race; Centers for Disease Control and Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and lipodystrophy. Differences were found in age (conditional logistic regression odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1); homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count <200 cells/µL (OR, 34.3; 95% CI, 4.3-277); diabetes mellitus (OR, 8.8; 95% CI, 1.6-49); alanine aminotransferase level higher than normal (OR, 13.0; 95% CI, 2.7-63); alkaline phosphatase higher than normal (OR, 18.3; 95% CI, 4.0-85); and platelets lower than normal (OR, 20.5; 95% CI, 2.4-178). Cumulative exposure to antiretroviral therapy (OR per year, 1.3; 95% CI, 1.0-1.6), nucleoside reverse-transcriptase inhibitor (OR, 1.3; 95% CI, 1.1-1.7), didanosine (OR, 3.4; 95% CI, 1.5-8.1), ritonavir (OR, 1.4; 95% CI, 1.0-1.9), and nelfinavir (OR, 1.4; 95% CI, 1.0-1.9) were longer in case patients. Exposure to nonnucleoside reverse-transcriptase inhibitor and other protease inhibitors were not different between groups. In bivariable models, only the association of NCPH with didanosine exposure was robust; other covariables were not independent risk factors. Conclusions. We found a strong association between prolonged exposure to didanosine and the development of NCP

HIV-Specific Cellular Immune Response Is Inversely Correlated with Disease Progression as Defined by Decline of CD4+ T Cells in Relation to HIV RNA Load

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is ∼8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes. HIV-specific CD4+ T cell responses and, to a lesser extent, HIVspecific CD8+ T cell responses were inversely correlated with progression rate. Slower progression was not related to polymorphisms in CCR genes, HLA genotype, or GB virus C coinfection. These data suggest that HIV-specific T cell responses are involved in protecting the host from disease progressio

High Prevalence of Anorectal Chlamydial Infection in HIV-Infected Men Who Have Sex with Men in Switzerland

Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) were enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal Chlamydia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic patients and patients having >20 sexual partners. These results support routine anorectal Chlamydia screening in HIV-infected MSM who report unprotected anal intercours

Screening HIV-positive men who have sex with men for hepatitis C re-infection risk: is a single question on condom-use enough? A sensitivity analysis

Hepatitis C virus (HCV) is common in men who have sex with men (MSM) with HIV. The Swiss HCVree Trial targeted a micro-elimination by using a treat and counsel strategy. Self-reported condomless anal intercourse with non-steady partners was used as the selection criterion for participation in a counselling intervention designed to prevent HCV re-infection. The purpose of this study was to assess the ability of this criterion to identify men who engaged in other sexual risk behaviours associated with HCV re-infection.; Men who disclosed their sexual and drug- use behaviours during the prior 6 months, at study baseline, were included in the current study. Using a descriptive comparative study design, we explored self-reported sexual and drug-use risk behaviours, compared the odds of reporting each behaviour in men who reported and denied condomless anal intercourse with non-steady partners during the prior year and calculated the sensitivity/specificity (95% CI) of the screening question in relation to the other at-risk behaviours.; Seventy-two (61%) of the 118 men meeting eligibity criteria reported condomless anal intercourse with non-steady partners during the prior year. Many also engaged in other potential HCV transmission risk behaviours, e.g., 52 (44%) had used drugs. In participants disclosing drug use, 44 (37%) reported sexualised drug use and 17 (14%) injected drugs. Unadjusted odds ratios (95% CI) for two well-known risk behaviours were 2.02 (0.80, 5.62) for fisting and 5.66 (1.49, 37.12) for injecting drug use. The odds ratio for sexualised drug use - a potential mediator for increased sexual risk taking - was 5.90 (2.44, 16.05). Condomless anal intercourse with non-steady partners showed varying sensitivity in relation to the other risk behaviours examined (66.7-88.2%).; Although condomless anal intercourse with non-steady partners was fairly sensitive in detecting other HCV relevant risk behaviours, using it as the only screening criterion could lead to missing a proportion of HIV-positive men at risk for HCV re-infection due to other behaviours. This work also points to the importance of providing access to behavioral interventions addressing other sexual and drug use practices as part of HCV treatment.; Clinical Trial Number: NCT02785666 , 30.05.2016

Modern anti-HIV therapy

Highly active antiretroviral therapies (HAART), usually consisting of two nucleoside reverse transcriptase inhibitors (NRTI) plus an HIV protease inhibitor (PI), have been widely used since 1996. They produce durable suppression of viral replication with undetectable plasma levels of HIV-RNA in more than half of patients. Immunity recovers, and morbidity and mortality fall by more than 80% [1, 2]. Treatment was thought to be particularly effective when started early; therefore, HAART was recommended for essentially all HIV-infected persons willing to commit themselves to lifelong therapy [3, 4]. Besides these successes, however, HAART also produces problems. HIV is not eradicated by present-day drugs, and patients often cannot comply with long-term combination treatment [5, 6]. Moreover, HAART causes unexpected and ill-understood side effects [7]. The dogma of earliest possible treatment has therefore come under attack. Ten principles governing anti-retroviral treatment are summarised in Table 1. Starting and maintaining HAART is complex. Within the last few years, the numbers of antiretrovirals, their known and potential interactions with each other and with non-HIV drugs, and the list of their side effects have all increased exponentially. As a rule a physician specialising in HIV care should be consulted whenever HAART is started or changed. It is his task to ensure that the treatment chosen is optimal for the particular patient

Emergence of resistance to integrase strand transfer inhibitors during Dolutegravir containing triple-therapy in a treatment-experienced patient with pre-existing M184V/I mutation.

With the current widespread use of dolutegravir in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing antiretroviral therapy (ART) is of utmost importance. We describe a rare case of a patient with pre-existing M184V/I mutation and virological failure on a dolutegravir/lamivudine/abacavir regimen with the emergence of integrase strand transfer inhibitor resistance mutations. Additional risk factors, which may have triggered the virological failure, included suboptimal adherence and low nadir CD4+ cell count. This case illustrates that dolutegravir-containing triple-therapy should be prescribed with caution to patients with pre-existing M184V/I mutation and poor efficacy of the reverse transcriptase inhibitor backbone. In addition, this case highlights the need for viral load monitoring in patients on dolutegravir-containing regimens in settings with a high prevalence of the M184V/I mutation such as in low-income countries