Ken McLean

Transmission of HIV to heterosexual partners of infected men and women.

Future heterosexual spread of HIV will in part depend on the efficiency of transmission from men to women and from women to men. We studied seventy-eight female sexual partners of men infected with HIV and 18 male sexual partners of infected women. Participants were interviewed concerning sexual practices, use of contraception and other risk factors for HIV infection. Fifteen out of 78 (19.2%) female partners and one out of eighteen (5.5%) male partners were seropositive for HIV antibody. All couples had practised vaginal intercourse. Seropositive female partners did not differ significantly from seronegative partners with regard to length of relationship, number of acts of vaginal intercourse, other sexual practices, stage of clinical disease in the index case, or numbers of other sexual partners in the last five years. In two women, seroconversion was documented after one act of unprotected sexual intercourse. The majority of infected female partners (eight out of 15) had sexual relationships with men who were asymptomatic and did not practice anal intercourse. Biological factors such as variability in infectivity of the index case and susceptibility of the contact, as well as behavioural variables may be important in determining transmission.

Disorders of fat distribution in HIV infection

Alterations in body shape due to fat loss and/or redistribution have been described in HIV-infected individuals and associated with the use of antiretroviral (ARV) combination therapy. Certain of these changes have been referred to as peripheral lipodystrophy (LD) and we describe 12 patients who were recognized with this condition between September 1997 and February 1998. It occurred in 12.5% of patients on ARV combination therapy that included a protease inhibitor (PI). In early descriptions the emphasis was on the abdomen, which may be grossly enlarged. In our patients this feature was much less marked. Patients with LD were significantly older than those on PI therapy who did not develop this condition ( P =0.016). Although all had raised triglyceride (TG) levels, the elevations were not severe (maximum=6.3 mmol/l). CD4 lymphocyte and viral load levels suggested an optimal response to ARV therapy at the time LD developed. Appearances may be disfiguring but no serious systemic consequences of LD have been observed. Most individuals have chosen to remain on their present ARV combinations. When LD occurs, it appears to be a marker of effective response to anti-HIV therapy.

Survival following HIV infection of a cohort followed up from seroconversion in the UK.

Objectives: To estimate changes over calendar time in survival following HIV seroconversion in the era of HAART and to provide updated survival estimates. Methods: Using data from a UK cohort of persons with well estimated dates of HIV seroconversion, we analysed time from seroconversion to death from any cause using Cox models, adjusted for prognostic factors. Kaplan–Meier methods were then used to determine the expected survival in each calendar period. Results: 2275 seroconverters were included with 18 695 person-years of follow up. A total of 444 (20%) died. The relative risk of death, compared with pre-1996, decreased over time to 0.63 [95% confidence interval (CI), 0.48–0.81], 0.24 (0.17–0.34), 0.14 (0.10–0.21), 0.08 (0.05–0.13) and 0.03 (0.02–0.06) in 1996–1997, 1998–1999, 2000–2001, 2002–2003 and 2004–2006, respectively. An elevated risk of death was associated with older age at seroconversion [hazard ratio (HR), 1.49; 95% CI, 1.34–1.66 per 10-year increase] and HIV infection through injecting drug use (HR, 1.53; 95% CI, 1.17–2.00). In 2000–2006, the proportion of individuals expected to survive 5, 10 and 15 years following seroconversion was 99%, 94% and 89%, respectively. Conclusions: Survival following HIV seroconversion has continued to improve over calendar time in our cohort, even in the more recent years of HAART availability. HIV seroconverters, by definition identified early in their infection, are likely to have the greatest opportunity for intervention; if similar high survival expectations are to be seen in the wider HIV-infected population, early diagnosis is likely to be crucial.

Effect of human immunodeficiency virus-1 protease inhibitors on the clearance of human herpesvirus 8 from blood of human Immunodeficiency virus-1-infected patients

The effect of human immunodeficiency virus‐1 protease inhibitors on the frequency of human herpesvirus 8 DNA detection from peripheral blood of human immunodeficiency virus‐positive persons was evaluated. Thirty‐three human immunodeficiency virus‐seropositive male patients were studied longitudinally. DNA from open reading frame 26 of the human herpesvirus 8 genome was amplified by the polymerase chain reaction from the CD45+ fraction of peripheral blood before and after the introduction of protease inhibitor therapy. Human herpesvirus 8 IgG status, CD4+ cell counts, and human immunodeficiency virus‐1 plasma viral load were also assessed before and after therapy. When both reverse transcriptase inhibitor and protease inhibitor treatment were introduced at the same time, there was an increase in CD4+ T cell counts (P=0.0041), a decrease in human immunodeficiency virus plasma load (P=0.0584), and a decrease in the detection rate of human herpesvirus 8 DNA (P=0.0077). Introducing protease inhibitor to patients already receiving reverse transcriptase inhibitor treatment was associated with an increase in CD4+ T cell counts (P=0.0003), a decrease in human immunodeficiency virus plasma viral load (P=0.0911), and a decrease in the human herpesvirus 8 detection rate (P=0.0412). No significant changes in the titters of anti‐human herpesvirus 8 IgG were observed. Treatment with human immunodeficiency virus‐1 protease inhibitors is therefore associated with the clearance of human herpesvirus 8 DNA from peripheral blood of human immunodeficiency virus‐infected patients. The concomitant decrease in the human immunodeficiency virus plasma load and increase in the peripheral CD4+ cell count suggest that an amelioration in the immune defect following reduction in the burden of human immunodeficiency virus‐1 infection is responsible for the clearance of human herpesvirus 8 by protease inhibitors. J. Med. Virol. 62:416–420, 2000.

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

Background The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. Methods Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion). Results Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively. Conclusion Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.

Atrial myxoma and HIV infection

Editor,—Atrial myxoma has not previously been reported in HIV infection. We describe a patient with advanced HIV disease who underwent surgery for this condition. The patient was diagnosed with asymptomatic HIV infection in February 1987 when she was aged 50 years. Her CD4 count was 690 ×106/l at this time. HIV infection was acquired through sexual intercourse with a bisexual male partner. In December 1990 the CD4 lymphocyte count had fallen to 190 ×106/l and zidovudine monotherapy was started. This was continued until 1996 when she was prescribed a combination regimen. Co-trimoxazole was given …

Chaperoning in GUM clinics

In the report by the MSSVD on chaperoning in genitourinary medicine (GUM) clinics, it was suggested that patient acceptability with regard to chaperoning needed to be assessed.1 We have recently completed a survey on patients attending our GUM clinic looking at our practice for offering chaperones for intimate examinations. A proforma was completed by senior full time doctors before clinical examination of patients requiring such procedures. The survey took place over consecutive clinical sessions in June 2003. The sheet documented the patient’s details, member of staff examining, and whether a chaperone was offered. Reasons for either not offering a chaperone …

Recurrent hypersensitivity to Combivir.

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly used in combination antiretroviral therapy and are associated with hypersensitivity reactions on induction therapy. We report a case of recurrent hypersensitivity associated with Combivir, when there was a delay in determining the cause as the NNRTIs were considered to be the more likely cause.

The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK.

Introduction The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown. Methods We used data from a cohort of HIV seroconverters to investigate the effect of HCV infection duration on time from HIV seroconversion to CD4 <350cells/mm3, AIDS or death, censoring at the earlier of cART initiation or last clinic visit, adjusting for confounders and splitting data into follow up periods from HIV seroconversion (<2, 2–4 and >4 years). We additionally compared CD4 cell decline following HCV infection to that of mono-infected individuals with similar HIV infection duration by fitting a random effects model. In a separate analysis, we used linear mixed models to we examine the effect of HCV infection and its duration on CD4 increase over 48 weeks following cART. Results Of 1655 individuals, 97 (5.9%) were HCV co-infected. HCV<1 year was associated with a higher risk of endpoint in each follow-up period from HIV seroconversion (HR [95% CI] 2.58 [1.51, 4.41], p = 0.001; 3.80 [1.20, 12.03], p = 0.023; 2.03 [0.88, 4.71], p = 0.098 for <2, 2–4 and >4 years respectively), compared to mono-infected individuals. However, we found no evidence of an association for those with HCV>2 years (all p>0.89). Individuals experienced a somewhat greater decrease in CD4 count following HCV infection lasting 13 months, relative to individuals with HIV alone, (estimate = -3.33, 95% CI [-7.29, 0.63] cells/mm3 per month, p = 0.099). Of 1502 initiating cART, 106 (7.1%) were HCV co-infected, with no evidence of HCV duration at cART being associated with immunological response (p = 0.45). Conclusions The impact of HCV co-infection on HIV disease progression appears to be restricted to the first year after HCV infection.