Demographics in HIV-infected children in Denmark: results from the Danish Paediatric HIV Cohort Study

We present the demographic data on HIV-infected children from the Danish Paediatric HIV Cohort Study, an observational database on HIV in Denmark. Up to 1 July 2003 a total of 89 children had been diagnosed with HIV infection before the age of 16 y, of which 12 (13.5%) had died, 2 (2.2%) had emigrated from Denmark, and 13 had reached the age of 16 y. Estimates of prevalence and incidence of HIV infection in the area were 5.77/100,000 and 0.39/100,000 respectively, which are lower than in the adult population. After 1993 the number of newly diagnosed HIV infected children remained quite constant with an average of 4.2 diagnoses per y. Of the enrolled patients only 15.7% had both their parents of Danish origin, while 58.5% had at least 1 of the parents from an African country. Of the entire cohort, 20% were Caucasians, 51% were males and 76% were infected perinatally. There has been a shift in the HIV epidemic in children over recent y, with a higher proportion of newly diagnosed HIV patients having contracted the infection perinatally, a higher proportion being of non-Caucasian race, and the newly diagnosed individuals being younger. Even since 1995, a major part of the newly diagnosed children was born in Denmark by mothers from high-endemic areas and we therefore suggest that HIV-testing should actively be offered to all pregnant women coming from these high-risk areas.     

Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection. Swiss HIV Cohort Study

OBJECTIVE AND METHODS: In 1998 we reported on a randomized comparison between stavudine plus didanosine plus placebo versus stavudine plus didanosine plus hydroxyurea (HU), in patients with a CD4 count of 200-500 x 10(6) cells/l. After 3 months, the HU group had a higher proportion of patients with viral load < 200 x 10 cells/l. At the end of the 3 months blinded period, patients in the placebo group had the option to add HU if their viral load remained > 200 x 10(6) cells/l. We report results after 24 months. RESULTS: Seventy-two patients were randomized to the HU arm, and a further 30 elected to add HU after 12 weeks. Twenty-four months after the start of the trial, only 25% of the 72 patients originally randomized to HU, and 20% of the 30 who added HU after week 12, were still taking it. The reasons for stopping HU were: lack of efficacy (45%), adverse events (37%) and patient or physician preference (18%). Side effects were more frequent in the didanosine/stavudine/HU group than in the didanosine/stavudine group: neuropathy (35 versus 15%, P< 0.02), fatigue (22 versus 7%, P< 0.01), and nausea or vomiting (26 versus 9%, P< 0.01). Of those who had discontinued HU, 73% were taking three drugs including a protease inhibitor. Patients who had started HU were compared with similar patients who had started protease inhibitors in the Swiss cohort. The probability of stopping HU was higher than the probability of stopping nelfinavir or indinavir, and similar to the probability of stopping ritonavir. CONCLUSION: HU increased the antiviral effect of stavudine plus didanosine. However, side effects were more frequent, and after 24 months the majority of patients had switched to protease inhibitor regimens.     

HIV-2 infection in Denmark.

A collection of 3019 selected serum samples (ss), comprising 329 ss from intravenous drug abusers, 558 ss from homosexual men, 682 samples from persons attending a STD clinic, 100 ss from individuals of African origin, 300 ss from sexual contacts to Africans, 650 ss from Danish blood donors who resided in Africa greater than 2 years prior to donating the ss, and 400 ss with equivocal antibody reactions in an HIV-1 Western blot was tested for antibodies against HIV-2 by in-house HIV-2 ELISA and Western blot. Four ss were positive for antibodies against HIV-2. Three of the ss originated from West African men, the fourth belonged to the spouse of one of these men. Three of the samples presented with an uncharacteristic reaction in a HIV-1 Western blot. The study indicates that HIV-2 infection is not yet widespread in Denmark and that it remains closely related to West Africa.     

CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study

BACKGROUND: Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-1 infection allows recovery of CD4 T lymphocytes. Few studies have explored the long-term T-lymphocyte responses to HAART. METHODS: Plasma HIV-1 RNA levels and CD4 and CD8 T-lymphocyte counts were longitudinally analyzed over 4 years in 2235 participants of the Swiss HIV Cohort, commencing HAART between 1996 and 1997. The CD4 T-lymphocyte count increase, the percentage of individuals with a CD4 T-lymphocyte count of 500/microL or greater and less than 200/microL, and the determinants of CD4 T-lymphocyte recovery were evaluated in individuals treated with continuous (CONT; n = 985) and discontinuous (DISCONT; n = 1250) HAART. RESULTS: At 4 years, 69.5% of subjects (CONT, 84.5%; DISCONT, 53.6%; P<.001) showed HIV-1 RNA levels below 400 copies/mL, while the median CD4 T-lymphocyte count increased from 190/microL to 423/microL (CONT, 486/microL; DISCONT, 343/microL; P<.001). Of the 2235 participants, 38.8% (CONT, 47.7%; DISCONT, 29.4%; P<.001) reached a CD4 T-lymphocyte count of 500/microL or greater, but in 15.6%, CD4 T-lymphocyte count remained below 200/microL (CONT, 5.9%; DISCONT, 25.9%; P<.001). Larger increases in CD4 T-lymphocyte count were associated with higher baseline HIV-1 RNA, a larger percentage of undetectable HIV-1 RNA levels, lower baseline CD8 T-lymphocyte count, and younger age. Individuals reaching a CD4 T-lymphocyte count of 500/microL or greater at 4 years were characterized by higher nadir and baseline CD4 T-lymphocyte counts and a more sustained reduction of HIV-1 RNA levels. CONCLUSIONS: At 4 years, only 39% of individuals treated with HAART reached a CD4 T-lymphocyte count of 500/microL or greater, and 16% with CD4 T-lymphocyte counts less than 200/microL remained susceptible to opportunistic infections. Treatment interruptions, a poor virologic response, and older age were the major factors negatively affecting the recovery of CD4 T lymphocytes.     

Time of initiation of antiretroviral therapy: impact on HIV-1 viraemia. The Swiss HIV Cohort Study

OBJECTIVE: The current recommendation that patients infected with HIV-1 be treated early is based on little evidence. We examined whether the early initiation of antiretroviral treatment affects residual HIV-1 viraemia. METHODS: Viraemia was measured using an assay with a detection limit of 3 HIV-1 RNA copies/ml in drug-naive patients who started antiretroviral therapy at the time of primary HIV-1 infection (PHI) (n = 10), during chronic infection without immune suppression (CD4 cell counts > or = 500/mm3; median 577) (n = 10), or after immune suppression developed (CD4 cell counts < 500/mm3; median 113) (n = 21). RESULTS: In 249 samples collected 24 to 120 weeks after treatment initiation, the mean proportion of samples with HIV-1 RNA levels of less than 3 copies/ml was 75% for PHI patients compared with 32 and 8% for immunocompetent and immunosuppressed chronically infected patients, respectively. Fifty per cent of PHI patients, but none of the chronically infected patients, had persistently fewer than 3 HIV-1 RNA copies/mL. PHI patients had lower residual HIV-1 RNA levels than chronically infected patients, and immunocompetent patients had lower residual HIV-1 RNA levels than immunosuppressed patients (all pairwise, P< 0.001). The mean residual HIV-1 RNA level was independently associated with the initiation of therapy during PHI and baseline CD4 cell counts (P < 0.001 for both associations). CONCLUSION: Viraemia levels are associated with clinical progression and predict virological treatment failure. The initiation of antiretroviral therapy at the time of PHI and while CD4 cell counts are high results in lower residual viraemia. These results support early antiretroviral therapy in HIV-1-infected patients.     

The epidemiology of HIV-1 infection in northern Tanzania: results from a community-based study

We conducted a community-based study to determine the predictors of HIV-1 among women aged 20-44 years (N = 1,418) and their regular male partners (N = 566) from randomly selected households in Moshi, Tanzania. The weighted prevalence of HIV-1 was 10.3% in women and 7% in men. The highest risk of HIV-1 was in subjects whose partners were HIV-1 seropositive in both women (adjusted odds ratio (AOR) = 26.63; 95% confidence interval (CI): 10.74-66.02) and men (AOR = 22.25; 95%CI: 7.06-70.15). Herpes simplex virus type 2 (HSV-2) and Mycoplasma genitalium were also significantly associated with HIV-1. Women with male partners >or=12 years older than themselves had increased risk of HIV-1 (AOR = 1.99; 95%CI: 1.01-7.85). Other predictors of HIV-1 were history of infertility and the number of sex partners in the last three years in women and the age at time of circumcision and history of past sexually transmitted diseases (STDs) in male partners. These findings show that HIV-1/STDs were major public health problems among women and their long-term partners in this population. HIV-1 prevention efforts should include promotion of couple's HIV-1 counseling and testing services, control of HSV-2, promotion of safer sexual practices and strategies to reduce the age difference between women and their partners.     

HIV-1 subtypes in Denmark.

The objective of this study was to investigate the presence of non-subtype B HIV-1 in Denmark. The C2-V3-C3 region of the env gene from proviral DNA obtained from patients suspected of being infected with non-subtype B virus was PCR-amplified and directly sequenced. The DNA sequences were aligned with full-length HIV-1 reference strains from each subtype and analysed using the phylogenetic package PHYLIP 3.1. The neighbour-joining method was used with 100 bootstraps. Of the 144 patients included in this study C2-V3-C3 sequences were obtained from 129 patients (90%). The phylogenetic analyses showed that virus from 49 patients (38%) was subtype A, 39 (30%) subtype C, 9 (7%) subtype D, 14 (11%) subtype CRF01_AE, 16 (12%) subtype B, 1 (1%) subtype F and 1 (1%) subtype J. This study demonstrates that almost all subtypes can be detected in Denmark; all non-subtype B infections could be traced to countries with a high prevalence of non-subtype B virus.     

Causes of death among patients with HIV in Singapore from 1985 to 2001: results from the Singapore HIV Observational Cohort Study (SHOCS)

OBJECTIVES: To investigate the major primary and contributory causes of death among HIV patients in Singapore. DESIGN: A retrospective observational cohort study of all adult patients seen at the national referral centre for HIV in Singapore between 1985 and 2001. METHODS: Data were extracted from the patients' records by 10 trained health care workers. AIDS-defining conditions were established using predefined criteria. For each case, a single principal cause of death and up to three contributory causes were identified. RESULTS: A total of 1504 patients aged 17 years or over were seen before the end of 2001, of whom 504 have died. The most frequent principal causes of death were Mycobacterium avium (17.5%), Mycobacterium tuberculosis (9.7%), pneumonia (cause unknown) (6.5%) and Cryptococcus neoformans (6.7%). Three hundred and eighteen patients (63.1%) died from an AIDS-defining condition. CONCLUSIONS: The causes of death were similar to those found in Western cohorts, except that disseminated M. avium was a more frequent cause of death.     

Early control of HIV replication in primary HIV-1 infection treated with antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS 086) Study

IFN alpha has both antiviral and immunostimulating properties. The ANRS086 Primoferon A Study evaluated in 12 patients with primary HIV infection the tolerance and efficacy of an early and transient administration of pegylated IFN alpha, in addition to highly active antiretroviral therapy. Tolerance was good, and this regimen allowed the early control of HIV replication and rapid decay of the viral reservoir. These results support the initiation of comparative studies with pegylated INF alpha in primary HIV infection.     

Mixed cryoglobulinemia in HIV-1 infection: the role of HIV-1

BACKGROUND: Cryoglobulins are associated with chronic infections. OBJECTIVE: To investigate the prevalence of mixed cryoglobulinemia in patients with HIV-1 infection, the clinical spectrum of cryoglobulinemia in these patients, and the possible role of HIV-1 in cryoglobulin formation. DESIGN: Prospective cohort study. SETTING: Laiko Hospital, Athens, Greece. PATIENTS: 89 patients with HIV-1 infection. MEASUREMENTS: Serum and cryoglobulins were evaluated for antibodies to HIV and hepatitis C virus (HCV), HIV-1, and HCV viral load. RESULTS: Mixed cryoglobulins were detected in 24 patients with HIV-1 infection (27% [95% CI, 18% to 36%]). The HIV-1 viral load was higher in cryoglobulin-positive patients (median, 38.25 x 10(3) copies/mL [25th, 75th percentiles: 13.8 x 10(3) copies/mL, 78.55 x 10(3) copies/mL]) than in cryoglobulin-negative patients (median, 5.3 x 10(3) copies/mL [25th, 75th percentiles: 0.7 x 10(3) copies/mL, 27.2 x 10(3) copies/mL]) (P = 0.001). Antibodies to HIV were detected in all cryoprecipitates, and HIV-1 RNA sequences were identified in 22 of the 23 cryoprecipitates examined. Nine cryoglobulin-positive patients (38% [CI, 19% to 54%]) had clinical manifestations compatible with cryoglobulinemia. CONCLUSIONS: Mixed cryoglobulinemia is common in patients with HIV-1 infection.     

Intrafamilial transmission of HIV-1 infection from individuals with unrecognized HIV-1 infection

OBJECTIVE: To describe the clinical, epidemiological and molecular evidence for transmission of HIV-1 infection from a person with unrecognized HIV infection to a family member in two unconnected families where the route of transmission could not be conclusively determined. DESIGN: Case studies, molecular analysis of viral strains and a clinical and laboratory investigation of risk factors for transmission. SETTING: State referral centres for HIV/AIDS in two Australian teaching hospitals. RESULTS: Previously unrecognized HIV-1 infection was diagnosed in two unconnected females following blood donation in different Australian cities. Initially, no source of infection was identified but subsequently HIV-1 infection was diagnosed in the sister of one case and the adult son of the other. Using nucleic acid-based methods, it was demonstrated that one index case and her sister were infected with highly homologous 'Russian-type' HIV-1 subtype A, and the other index case and her son were infected with highly homologous HIV-1 subtype E (CRF01_AE). Sexual history taking from the sister and the son of the respective index cases revealed prior sexual partners from geographical areas in which the corresponding subtypes are known to be prevalent. Extensive history taking, cross-validated by independent reviewers, found no evidence whatsoever that any form of sexual contact or known blood contact could explain the HIV-1 infection in the two index cases. However, there was evidence that some form of domestic contact involving unperceived blood transfer may have occurred. CONCLUSION: Intra-familial transmission of HIV-1 infection should be considered when a source of HIV-1 infection cannot be determined.     

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study

Objectives

To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study.

Methods

Two sub‐populations were included: 1915 patients with HIV diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment‐naïve patients with CD4≥200 cells/μL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/μL without ART despite cohort follow‐up.

Results

Median initial CD4 cell count in group A was 331 cells/μL; 31% and 10% were <200 and <50 cells/μL, respectively. Risk factors for low CD4 count were age and non‐White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4≥200 cells/μL; 18% and 2% dropped to CD4 <200 and <50 cells/μL without ART, respectively. Sub‐Saharan origin was associated with lower probability of CD4 <200 cells/μL without ART during follow‐up. Median CD4 count at ART initiation was 207 and 253 cells/μL in groups A and B, respectively.

Conclusions

CD4<200 cells/μL and, particularly, CD4<50 cells/μL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.     

HIV infection is not associated with Reiter's syndrome: data from the Johns Hopkins Multicenter AIDS Cohort Study

Reiter's syndrome has been reported to occur in up to 10% of patients with HIV infection. However, no properly controlled epidemiological studies have been conducted to determine whether HIV infection is an independent risk factor or whether the immunodeficiency induced by HIV infection is permissive for infection with other arthritogenic organisms. The prevalence and incidence of Reiter's syndrome were determined in 1133 homosexual/bisexual men enrolled in the Johns Hopkins Multicenter AIDS Cohort Study. There was no difference in the prevalence of Reiter's syndrome at entry into the study in 1984 between 357 HIV-positive and 776 HIV-negative men: five per 1000 in both groups. During 5 years' follow-up, one case of Reiter's syndrome developed among each group of HIV-positive and HIV-negative men. These data fail to support a direct etiological role for HIV infection in the development of Reiter's syndrome.     

Stopping primary prophylaxis in HIV-1-infected patients at high risk of toxoplasma encephalitis. Swiss HIV Cohort Study

Discontinuation of primary prophylaxis against toxoplasma encephalitis was studied in 199 HIV-1-infected patients on antiretroviral combination treatment who had experienced a sustained increase in their CD4 count. During a follow-up of 272 person-years, no cases of toxoplasma encephalitis arose.     

AIDS-defining illnesses among patients with HIV in Singapore, 1985 to 2001: results from the Singapore HIV Observational Cohort Study (SHOCS)

Background  

The objective was to describe the causes of initial and overall AIDS-defining disease episodes among HIV patients in Singapore.