Treatment Of Primary HIV Infection Research Articles

Follow-up and treatment of primary HIV infection in Pregnancy

Follow-up and treatment of primary HIV infection in Pregnancy

HIV-1-RNA and total HIV-1-DNA loads in the genital compartment in men receiving dolutegravir- versus darunavir-based combined ART (cART) regimens during primary HIV infection.

Dolutegravir is a widespread integrase strand-transfer inhibitor (INSTI) recommended for treatment of primary HIV infection (PHI). PHI is a high-risk stage for sexual transmission because of the high viral load in semen. Yet dolutegravir concentrations in semen are lower than in blood during chronic treatment. To compare the kinetics of HIV-RNA and total HIV-DNA in the genital compartment in subjects receiving either tenofovir/emtricitabine/dolutegravir or tenofovir/emtricitabine/darunavir/cobicistat as a first-line combined ART (cART) at the time of PHI. Eighteen subjects receiving tenofovir/emtricitabine/dolutegravir and 19 receiving tenofovir/emtricitabine/darunavir/cobicistat enrolled in the ANRS169 OPTIPRIM-2 trial participated in the genital substudy. Between week (W) 0 and W2 HIV-RNA in seminal plasma (SP) decreased by 1 log10 copies/mL. Undetectable SP HIV-RNA was achieved in similar proportions between the two regimens at each timepoint. Overall, eight patients still presented detectable HIV-RNA or HIV-DNA in semen at W48; 15.4% and 28.6% presented detectable HIV-RNA and 9.1% and 14.3% presented detectable HIV-DNA in dolutegravir- and darunavir-based cART groups, respectively, with no significant difference. For the first time, to the best of our knowledge, we showed that a dolutegravir-based regimen initiated as soon as PHI reduces HIV-RNA and HIV-DNA with no difference compared with a control group receiving a darunavir-based regimen. Although the viral purge in semen seems longer after treatment in PHI than CHI, due to high viral loads, early dolutegravir-based treatment initiation permits a major decay of both viral particles and infected cells in semen, efficiently reducing the high risk of transmission during PHI.

Treatment of primary HIV infection: new data for a new era.

Treatment of primary HIV infection: new data for a new era.

Compromised CD4:CD8 ratio recovery in people living with HIV agedover 50 years: an observational study.

ObjectivesPersistent CD4:CD8 ratio inversion (< 1) is associated with mortality in older people. We investigated the interaction of the effects of baseline CD8 count and age at HIV diagnosis on CD4:CD8 ratio recovery with antiretroviral therapy (ART).MethodsAn observational study (1 January 2007 to 31 December 2016) was carried out using routinely collected data from the HIV outpatient services at Imperial College Healthcare NHS Trust, London, UK. CD4 and CD8 counts, prior to and during ART, treatment during primary HIV infection (PHI) and HIV‐1 viral load were included in univariate and multivariate analyses using Cox proportional hazard regression.ResultsData were included for 876 patients starting ART, where HIV suppression was achieved. Of these patients, 741 of 876 (84.6%) were male and 507 of 876 (57.9%) were Caucasian. The median time on ART was 38 [interquartile range (IQR) 17–66] months. CD8 count change on ART was bidirectional; low CD8 counts (≤ 600 cells/μL) increased and high CD8 counts (> 900 cells/μL) decreased. The median pre‐ART CD4:CD8 ratio was 0.41 (IQR 0.24–0.63), and recovery (≥ 1) occurred in 274 of 876 patients (31.3%). Pre‐ and post‐ART CD4:CD8 ratios were lower in those aged > 50 years compared with young adults aged 18–30 years (P < 0.001 and P = 0.002, respectively). After adjustment, younger age at HIV diagnosis (P < 0.001) and treatment during PHI (P < 0.001) were favourable for CD4:CD8 ratio normalization.ConclusionsOlder age (> 50 years) at HIV diagnosis was associated with persistent CD4:CD8 ratio inversion, whereas treatment of PHI was protective. These findings confirm the need for testing and early treatment of people aged > 50 years, and could be used in a risk management algorithm for enhanced surveillance.

Early Treatment of Primary HIV Infection Is Associated with Decreased Mortality.

The aim of this study was to understand factors associated with increased mortality in a cohort of primary HIV infection (PHI) in New South Wales (NSW) over three decades. Six hundred and two patients with PHI were enrolled from 1984 to 2009. Probabilistic data linkage was performed to NSW Registry of births deaths and marriages and Australian Bureau of Statistics mortality database. Mortality was measured by crude death rate. Pre highly active antiretroviral therapy (pre-HAART) era was defined as before January 1, 1997. A Cox proportional hazard model was used to identify factors associated with death. One hundred and thirty-eight deaths occurred during 6,223 person years (PY) follow-up. Overall crude death rate was 2.2 per 100 PY (95% confidence interval [CI], 1.9-2.6), 3.6 (95% CI, 3.1-4.3)in pre-HAART era and 0.20 (95% CI, 0.08-0.47) in post-HAART era. AIDS was the most frequent cause of death (52%, 72/138), all occurring in the pre-HAART era. Of non-AIDS deaths, the leading known cause was non-AIDS cancer 8% (11/138) followed by suicide 4% (6/138). On multivariate analysis, estimated date of infection in pre-HAART era and time to commencement of ART greater than 1 year post diagnosis were more likely to be associated with death (p < .05). Mortality in PHI has decreased significantly in the post-HAART era. Non-AIDS deaths due to malignancy and suicide are emerging as leading causes in this population in the post-HAART era. Time to starting ART greater than 1 year was associated with increased mortality.

Primary HIV Infection: Clinical Presentation, Testing, and Treatment.

The purpose of this review was to provide current data on clinical presentation, diagnosis, and treatment of primary HIV infection (PHI). In 65 to 95% of cases, PHI causes acute retroviral syndrome presenting with unspecific flu-like symptoms. Symptomatic PHI was associated with a faster clinical and immunological progression of HIV infection. Point-of-care tests remain less sensitive than fourth-generation immunoassays (IA) in PHI, especially after tenofovir-based prophylaxis use. Early antiretroviral treatment (ART) started during PHI prevents HIV transmission and decreases viral and immunological reservoir constitution. Recommended ART regimens in PHI are combinations of tenofovir and emtricitabine with either darunavir/ritonavir, or dolutegravir. Starting ART the earliest is highly recommended for clinical, virological, immunological, and public health benefits. Reducing HIV reservoir constitution in PHI may optimize potential opportunities for future functional cure.

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection.

BackgroundNeutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks.MethodsPrimo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment.ResultsAt viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point.ConclusionThese data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.

2.0 Recommendations and auditable outcomes

2.0 Recommendations and auditable outcomes

4.0 When to start

4.0 When to start

Improved Treatment for Primary HIV Infection by Interferon-Alfa Therapy? Does HCV Treatment in HIV/HCV Coinfected Patients Help Us to Test This Hypothesis?

Improved Treatment for Primary HIV Infection by Interferon-Alfa Therapy? Does HCV Treatment in HIV/HCV Coinfected Patients Help Us to Test This Hypothesis?

Unusual primary HIV infection with colonic ulcer complicated by hemorrhagic shock: a case report

IntroductionTimely diagnosis of primary HIV infection is important to prevent further transmission of HIV. Primary HIV infection may take place without symptoms or may be associated with fever, pharyngitis or headache. Sometimes, the clinical presentation includes aseptic meningitis or cutaneous lesions. Intestinal ulceration due to opportunistic pathogens (cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii) has been described in patients with AIDS. However, although invasion of intestinal lymphoid tissue is a prominent feature of human and simian lentivirus infections, colonic ulceration has not been reported in acute HIV infection.Case descriptionA 42-year-old Caucasian man was treated with amoxicillin-clavulanate for pharyngitis. He did not improve, and a rash developed. History taking revealed a negative HIV antibody test five months previously and unprotected sex with a male partner the month before admission. Repeated tests revealed primary HIV infection with an exceptionally high HIV-1 RNA plasma concentration (3.6 × 107 copies/mL) and a low CD4 count (101 cells/mm3, seven percent of total lymphocytes). While being investigated, the patient had a life-threatening hematochezia. After angiographic occlusion of a branch of the ileocaecal artery and initiation of antiretroviral therapy, the patient became rapidly asymptomatic and could be discharged. Colonoscopy revealed a bleeding colonic ulcer. We were unable to identify an etiology other than HIV for this ulcer.ConclusionThis case adds to the known protean manifestation of primary HIV infection. The lack of an alternative etiology, despite extensive investigations, suggests that this ulcer was directly caused by primary HIV infection. This conclusion is supported by the well-described extensive loss of intestinal mucosal CD4+ T cells associated with primary HIV infection, the extremely high HIV viral load observed in our patient, and the rapid improvement of the ulcer after initiation of highly active antiretroviral therapy. This case also adds to the debate on treatment for primary HIV infection, especially in the context of severe symptoms and an extremely high viral load.

Antiretroviral treatment of primary HIV infection to reduce onward transmission

This review will discuss the role of antiretroviral therapy to treat primary HIV infection (PHI) as a strategy to prevent onward viral transmission. Novel technology has greatly enhanced the appreciation of the characteristics of recently transmitted HIV-1 variants. Recent primate data demonstrate marked enhanced infectiousness of viral variants isolated from acutely infected macaques compared with viruses isolated from animals in the chronic phase of disease. These data are supported by phylogenetic analyses of recently transmitted cases in humans, implying that individuals with PHI may contribute disproportionately to onward transmission at a population level. In the absence of randomized clinical trial data supporting individual benefit of antiretroviral therapy, targeting and treating individuals with PHI as a public health intervention strategy represent a paradigm shift from current treatment strategies based around proven individual benefit alone. However, there is increasing evidence that PHI contributes disproportionately to viral transmission at a population level and failure to incorporate the potential role PHI plays, particularly in focused epidemics, maybe a naïve omission of many of the current mathematical models evaluating the impact of universal test and treat on population-level HIV incidence.

Treatment interruption to boost specific HIV immunity in acute infection

To understand the potential benefits and limitations of the treatment of acute, or primary, HIV infection followed by supervised treatment interruptions as a strategy to augment immune responses. Although this strategy led to the short-term control of virus replication after treatment interruption, follow-up data showed limited durability of control, and additional studies of short-term treatment in primary HIV infection show either a modest or no long-term benefit on CD4 cell counts and viral loads when compared with no therapy. Studies of gut-associated lymphatic tissue provide insights into the limitations of this approach because there has already been a massive destruction of the CD4 memory T-cell compartment by the time of symptomatic primary HIV infection by AIDS-associated retroviruses, which occurs before the emergence of cellular immune responses. There is currently no confirmed benefit of treatment of primary HIV infection by antiviral therapy alone in terms of disease progression and HIV-specific T-cell responses once therapy is interrupted. Supervised treatment interruption in acute HIV infection treated by antiviral therapy alone should probably not be used as a therapeutic strategy. This approach should be differentiated from early treatment itself, with or without immune augmentation, which deserves further investigation.

Primary HIV infection

Primary HIV infection refers to the events surrounding acquisition of HIV infection. It is associated with a nonspecific clinical syndrome that occurs 2 to 4 weeks after exposure in 40% to 90% of individuals acquiring HIV. Patients identified before seroconversion often have very high plasma HIV RNA titers that, without treatment, gradually decrease to reach a set point. Treatment of primary HIV infection with highly active antiretroviral therapy does not prevent establishment of chronic infection. However, very early therapy could potentially decrease the viral set point, prevent viral diversification, preserve immune function, improve clinical outcomes, and decrease secondary transmission. These benefits have not yet been definitely demonstrated. Transmission of viral strains with decreased susceptibility to antiviral drugs has led to recommendations for resistance testing in primary infection before initiation of therapy. Immunomodulators and vaccines are also under study as adjuvant therapy for treatment of primary HIV infection.

Treatment for primary HIV infection: projecting outcomes of immediate, interrupted, or delayed therapy.

With limited data available on the optimal treatment of primary HIV infection, disease modeling can be used to project clinical outcomes and inform decision makers. The authors developed a simulation model to evaluate the clinical outcomes and life expectancy projections for three primary HIV infection treatment strategies: 1) continuous antiretroviral therapy (ART) initiated at CD4 count <350 cells/mm(3); 2) continuous ART initiated immediately on diagnosis of primary HIV infection; and 3) ART initiated on diagnosis followed by structured treatment interruption. Projected life expectancies for the three strategies were 23.92, 24.46, and 26.07 years, respectively. The impact of key variables was assessed in sensitivity analysis, with the structured treatment interruption strategy remaining the most effective over a broad range of inputs. The immunologic benefit associated with immediate therapy and the potential for antiretroviral resistance due to structured treatment interruption have the most important impact on the optimal strategy. Based on current data, immediate treatment on diagnosis of primary HIV infection followed by structured treatment interruption will likely yield the best outcome. These results can assist decision makers and those planning clinical trials in defining evidence-based performance measures for primary HIV infection treatment and future trials.

HAART cessation after treatment of primary HIV infection

HAART cessation after treatment of primary HIV infection

Treatment of indinavir sulfate induced urolithiasis in HIV-positive patients.

Indinavir sulfate is a protease inhibitor used of the treatment of primary HIV infection either as monotherapy or as part of antiretroviral treatment schemes. Approximately 10% of all patients develop urolithiasis with radiolucent stones consisting of indinavir. We present our results of the treatment in 11 HIV positive patients (9 men, 2 women), who developed Indinavir lithiasis after 5-8 months of antiretroviral therapy. Following the initial procedures (spasmoanalgetic drugs, ureteroscopy, double J-stent or nephrostomy), the patients were further treated by increasing diuresis and urinary acidification. All the patients responded well to the treatment, the obstruction was releieved and their renal function was restored to normal.

Study Protocol for the Evaluation of the Potential for Durable Viral Suppression After Quadruple HAART With or Without HIV Vaccination: The QUEST Study

Purpose: By protecting and stimulating HIV-specific CD4 cell responses, treatment of primary HIV infection (PHI) with potent quadruple HAART could lead to prolonged suppression of HIV replication after cessation of antiretroviral therapy. The QUEST trial investigates this hypothesis and aims to determine whether addition of a therapeutic vaccine to HAART increases the likelihood of prolonged viral suppression compared to HAART alone. Method: 148 patients with PHI were recruited. Participants were treated with open-label HAART for at least 76 weeks. Participants with sustained viremia <50 copies/mL were randomized to one of three 5-month, double-blinded study treatment groups: HAART alone, HAART + ALVAC-HIV (vCP1452), or HAART + ALVAC-HIV (vCP1452) + RemuneTM. After a further month of HAART alone, all treatment was stopped where plasma HIV-1 RNA remained at <50 copies/mL. Intensive virologic and immunologic monitoring during a 24-week observation period followed treatment interruption. Patients who met treatment reintroduction criteria were offered HAART rescue.

Study Protocol for the Evaluation of the Potential for Durable Viral Suppression After Quadruple HAART With or Without HIV Vaccination: The QUEST Study

Purpose: By protecting and stimulating HIV-specific CD4 cell responses, treatment of primary HIV infection (PHI) with potent quadruple HAART could lead to prolonged suppression of HIV replication after cessation of antiretroviral therapy. The QUEST trial investigates this hypothesis and aims to determine whether addition of a therapeutic vaccine to HAART increases the likelihood of prolonged viral suppression compared to HAART alone. Method: 148 patients with PHI were recruited. Participants were treated with open-label HAART for at least 76 weeks. Participants with sustained viremia <50 copies/mL were randomized to one of three 5-month, double-blinded study treatment groups: HAART alone, HAART + ALVAC-HIV (vCP1452), or HAART + ALVAC-HIV (vCP1452) + RemuneTM. After a further month of HAART alone, all treatment was stopped where plasma HIV-1 RNA remained at <50 copies/mL. Intensive virologic and immunologic monitoring during a 24-week observation period followed treatment interruption. Patients who met treatment reintroduction criteria were offered HAART rescue.

Antiretroviral Drug Development and Information on the Internet

The rapid growth of the Internet parallels advances in the treatment of primary HIV infection. Recent breakthroughs in the use of viral load testing have shifted the focus away from monotherapy to highly active antiretroviral therapy (HAART) with combination regimens. Currently, three classes of drugs are available for the treatment of primary HIV infection and include the nucleoside and non-nucleoside reverse transcriptase inhibitors and the protease inhibitors. A review of the historical development of these compounds and some Internet resources is presented.