Leo Flamholc

Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure

ObjectiveTo determine the sensitivity of 33 currently available and seven earlier tests for the detection of HIV or HIV antibody in primary HIV-1 infection, to estimate the duration of the ‘window period’ and the influence of early initiated antiretroviral treatment (ART). DesignA prospective cohort study of 38 patients with primary HIV-1 infection. ART was initiated at a median time of 13 (range 0–23) days after the onset of symptoms in 10 patients. Main outcome measuresThe time from infection to onset of symptoms and from onset of symptoms to the appearance of HIV antibody as measured by 36 different tests, and the start and duration of viraemia, as detected by four different tests. ResultsThe illness appeared 13–15 days after infection in 12 of 15 determinable cases, and seroconversion was detected within 1–2 weeks after the onset of illness by 27 of 30 currently available tests for HIV antibody, in contrast to the 2–7 weeks or more needed by the old tests. HIV RNA appeared during the week preceding the onset of illness and was detected in all subsequent samples, except when ART had been initiated, which also induced a delay of the antibody response. ConclusionMany tests for HIV or HIV antibody can now be employed for an early confirmation of primary HIV infection (PHI). Currently available screening tests proved much more sensitive than older tests, and seroconversion was usually detected within one month after infection. Consequently, in Sweden we now recommend only 3 months of follow-up after most cases of HIV exposure.

Herpes simplex virus--the most frequently isolated pathogen in the lungs of patients with severe respiratory distress

308 consecutive patients with severe or complicated respiratory tract infections underwent fiber-optic bronchoscopy in the search for a microbiological etiology. Protected brush specimens were used for bacterial cultures and bronchoalveolar lavage (BAL) for virus isolation and cytological examination. Herpes simplex virus (HSV) was the most commonly found pathogen and was isolated in 37 patients. 20 (54%) of them also had serological and/or cytological signs of HSV infection. 132 patients required assisted ventilation (AV) and in this group 34 (92%) of the 37 HSV positive patients were found. Isolation of HSV was significantly (p less than 0.001) associated with AV compared to patients not requiring AV. Of all patients treated with AV 26% had positive HSV isolation in conjunction with suspected acute lower respiratory infection. Coinfection with HSV and bacteria occurred in only 8 (22%) patients. HSV was more common in patients with burns (47%) compared to other patient groups such as patients with AIDS (3%) or other immunodeficiencies (9%).

Antiretroviral treatment of HIV infection: Swedish recommendations 2007

On 3 previous occasions, in 2002, 2003 and 2005, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. An expert group, under the guidance of RAV, has now revised the text again. Since the publication of the previous treatment recommendations, 1 new drug for the treatment of HIV has been approved – the protease inhibitor (PI) darunavir (Prezista®). Furthermore, 3 new drugs have become available: the integrase inhibitor raltegravir (MK-0518), the CCR5-inhibitor maraviroc (Celsentri®), both of which have novel mechanisms of action, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125). The new guidelines differ from the previous ones in several respects. The most important of these are that abacavir is now preferred to tenofovir and zidovudine, as a first line drug in treatment-naïve patients, and that initiation of antiretroviral treatment is now recommended before the CD4 cell count falls below 250/µl, rather than 200/µl. Furthermore, recommendations on the treatment of HIV infection in children have been added to the document. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels).

Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets

The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90‐90‐90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV‐1‐infected population in Sweden.

Minimal transmission of HIV despite persistently high transmission of hepatitis C virus in a Swedish needle exchange program

Summary.  The aim of this study was to examine the prevalence and incidence of HIV and hepatitis B and C (HBV and HCV) among injecting drug users in a Swedish needle exchange programme (NEP) and to identify risk factors for blood‐borne transmission. A series of serum samples from NEP participants enrolled from 1997 to 2005 were tested for markers of HIV, HBV and HCV (including retrospective testing for HCV RNA in the last anti‐HCV‐negative sample from each anti‐HCV seroconverter). Prevalence and incidence were correlated with self‐reported baseline characteristics. Among 831 participants available for follow‐up, one was HIV positive at baseline and two seroconverted to anti‐HIV during the follow‐up of 2433 HIV‐negative person‐years [incidence 0.08 per 100 person‐years at risk (pyr); compared to 0.0 in a previous assessment of the same NEP covering 1990–1993]. The corresponding values for HBV were 3.4/100 pyr (1990–1993: 11.7) and for HCV 38.3/100 pyr (1990–1993: 27.3). HCV seroconversions occurred mostly during the first year after NEP enrolment. Of the 332 cases testing anti‐HCV negative at enrolment, 37 were positive for HCV RNA in the same baseline sample (adjusted HCV incidence 31.5/100 pyr). HCV seroconversion during follow‐up was significantly associated with mixed injection use of amphetamine and heroin, and a history of incarceration at baseline. In this NEP setting, HIV prevalence and incidence remained low and HBV incidence declined because of vaccination, but transmission of HCV was persistently high. HCV RNA testing in anti‐HCV‐negative NEP participants led to more accurate identification of timepoints for transmission.

Enhanced and resumed GB virus C replication in HIV-1-infected individuals receiving HAART.

In patients co-infected with HIV-1 and GB virus C (GBV-C), the disappearance of GBV-C RNA has been associated with accelerated disease progression. We studied longitudinal GBV-C viral titres in 28 HIV-1/GVB-C co-infected individuals receiving HAART. During HAART, median GBV-C RNA titres increased from 95 to 6000 copies/ml (P < 0.001). In patients interrupting HAART, GBV-C-RNA titres decreased as HIV replication resumed. These findings further support the theory that GBV-C replication could depend on the dynamics of HIV progression.

Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish recommendations 2007

Abstract Prophylaxis and treatment with antiretroviral drugs and the use of elective caesarean section have resulted in a very low mother-to-child transmission of human immunodeficiency virus (HIV) during recent years. The availability of new antiretroviral drugs, updated general treatment guidelines and increasing knowledge of the importance of drug resistance, have necessitated regular revisions of the “Prophylaxis and treatment of HIV-1 infection in pregnancy” recommendations. For these reasons, The Swedish Reference Group for Antiviral Therapy (RAV) updated the 2007 recommendations at an expert meeting that took place on 25 March 2010. The most important revisions from the previous recommendations are: (1) it is recommended that treatment during pregnancy starts at the latest at gestational week 14–18; (2) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (3) lopinavir/r and atazanavir/r are equally recommended protease inhibitors; (4) if maternal HIV RNA is >50 copies/ml close to delivery, a planned caesarean section, intravenous zidovudine, oral nevirapine for the mother and post-exposure prophylaxis for the infant with 3 antiretroviral drugs are recommended; (5) for delivery at <34 gestational weeks, intravenous zidovudine and oral nevirapine for the mother and at 48–72 h for the infant is recommended, in addition to other prophylaxis; (6) intravenous zidovudine is not recommended when HIV RNA is <50 copies/ml and a caesarean section is performed; (7) it is recommended that prophylaxis for the infant is started within 4 h; (8) prophylactic zidovudine for the infant may be administered twice daily instead of 4 times a day, as was the case previously; and (9) the number of sampling occasions for the infant has been decreased.

Treatment of HIV infection: Swedish recommendations 2009

On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/µl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.

Differential Effects of Efavirenz, Lopinavir/r, and Atazanavir/r on the Initial Viral Decay Rate in Treatment Naïve HIV-1–Infected Patients

Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukeys post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.

Herpes simplex virus hepatitis in a renal transplant recipient: successful treatment with acyclovir.

Herpes simplex virus (HSV) hepatitis in adults is a rare and severe disease usually occurring in immunocompromised patients or pregnant women. We report on a case of primary HSV type I hepatitis in a 48-year-old male renal transplant recipient with successful outcome after acyclovir treatment.