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Background: Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, may be the infectious cause of KS. Its prevalence in the general population, on the basis of detection of the virus genome, is controversial. To investigate the seroprevalence, we measured antibodies to a recombinant capsid-related (lytic cycle) KSHV antigen and a latent antigen complex., Methods: We selected potentially immunoreactive capsid-related proteins of KSHV by expressing them as recombinant proteins and testing them in western blot assays. We used a truncated recombinant protein encoded by KSHV open reading frame 65 (orf 65) to develop a diagnostic enzyme-linked immunosorbent assay (ELISA) and tested sera from HIV-infected individuals with KS, HIV-uninfected patients with "classic" KS, other HIV risk groups, and blood donors. We also compared the antibody response to this capsid-related protein to the response to latent antigen(s) in an immunofluorescence assay., Findings: 77/92 (84%) sera from KS patients reacted with the KSHV orf 65 protein and 84/103 (81.5%) reacted with KSHV latent antigen(s). The dominant immunogenic region of orf 65 is within the carboxyterminal 80 aminoacids, a region with little sequence similarity to the related Epstein-Barr virus, suggesting that orf 65 is a KSHV specific antigen. Only three sera from patients with haemophilia (1/84) or from intravenous drug users (2/63) had KSHV specific antibodies in the orf 65 assay whereas none of these sera reacted with latent antigen. Antibodies to KSHV were also infrequently found in UK and US blood donors by either assay (UK, 3/174 with orf 65 and 4/150 with latent antigen; US, 6/117 with orf 65 and 0/117 with latent antigen). They were more common among HIV-infected gay men without KS (5/16 by orf 65 ELISA, 10/33 by IFA), HIV-uninfected STD clinic attenders (14/166 by IFA), and Ugandan HIV-uninfected controls (6/17 by orf 65 ELISA, 9/17 by IFA). Antibody reactivity to the orf 65 protein (ELISA) and to latent antigen(s) (IFA) was concordant in 89% of 462 sera tested but reactive blood donor sera were discordant in both assays. Four AIDS-KS sera were unreactive in both assays., Interpretation: The distribution of antibodies to both a capsid-related recombinant protein and latent antigen(s) of KSHV strongly supports the view that infection with this virus is largely confined to individuals with, or at increased risk for, KS. However, infection with KSHV does occur, rarely, in the general UK and US population and is more common in Uganda. Antibodies to latent antigen(s) or to orf 65 encoded capsid protein will not detect all cases of KSHV infection, and a combination of several antigens will probably be required for accurate screening and confirmatory assays.

The response of HIV-1 to initial zidovudine (ZDV) treatment was assessed in 11 patients with severe HIV disease. We quantified serum HIV-1 concentrations and mutations associated with ZDV resistance by culture-independent methods. There was a prompt fall in serum HIV-1 RNA within 1-2 days of treatment with maximum suppression by seven days, which was paralleled by changes in serum p24 antigen (p24 Ag). Serum RNA started to return to pretreatment levels within weeks. The HIV reverse transcriptase (RT) gene in most patients developed mutations associated with drug resistance within months and as early as 25 days on therapy in one patient. The codon changes were not sufficient to explain the early return of serum HIV-1 RNA levels and their patterns continued to evolve after patients stopped taking ZDV. The significance of these findings is discussed in relation to the limited long-term efficacy of ZDV. The dynamic time course of viral load and RT responses to ZDV is of particular importance in short-term interventions such as pregnancy.

The prevalence of antibody to HTLV-III has increased from 3.7% (4/107) amongst unselected British homosexual men attending a London sexually transmitted disease (STD) clinic during one week in March, 1982, to 21% (26/124) in those attending during one week in July, 1984. Seropositive men had a significantly higher prevalence of infection with hepatitis B virus than did seronegative men. 82% (27/33) of the seropositive men in 1984 were symptomless or had only local genito-urinary symptoms referable to the STD for which they were attending. The evidence suggests that HTLV-III was initially an imported but is now an endemic sexually transmitted agent. As of July, 1984, at least 2600 homosexual men in London would probably have been infected.

BW A515U (6-Deoxyacyclovir) is a pro-drug of acyclovir and almost 100% is absorbed orally. 250 mg orally 6-hourly for 10 days was given to 4 hepatitis B surface antigen/e antigen-positive carriers. No consistent effect on productive viral replication, as determined by serum DNA polymerase and DNA levels was observed. The changes that occurred in these markers and transaminases in 1 patient were attributed to a spontaneous depression of productive viral replication.

The prevalence of antibody against human immunodeficiency virus (anti-HIV), which rose among British homosexual/bisexual men attending a London sexually-transmitted-disease clinic from 3.7% (4/107) in March, 1982, to 21% (26/124) in July, 1984, was 18.1% (17/94) in April/May 1985, 24.5% (61/249) in January, 1986, and 25.3% (25/99) in November/December, 1986. This slower rise in anti-HIV prevalence coincided with a fall in the annual gonorrhoea rate from 15.3% in 1982 to 5.1% in the first half of 1986 in the same male homosexual clinic population. Over the same period a reduction in the number of sexual partners and a change to safer sexual practices has been documented among homosexual and bisexual men taking part in a prospective study of the natural history of HIV infection. These data support the value of continuing preventive efforts to control viral spread in the absence of an effective vaccine or therapy.

56 patients with frequently recurring genital herpes were treated in a randomised double-blind trial with either oral acyclovir 200 mg four times a day or placebo for 12 weeks. 29 patients received the drug and 27 the placebo. The mean recurrence rate per month of treatment was 1.4 in the placebo-treated patients and 0.05 in the acyclovir group. Median time to the first recurrence after the start of therapy was 14 days in the placebo group compared with 100 days in the acyclovir group. After the end of treatment the recurrence rate was similar in the two groups. Prophylactic oral acyclovir seems to be an effective treatment for patients with frequently recurring genital herpes.

Twenty-nine HBV carriers were randomised to receive ARA-AMP 10 mg/kg/day given as intramuscular injections 12 h apart for 5 days followed by 5 mg/kg/day for 23 days (15 patients) or no treatment (14 patients). Serum HBV-DNA polymerase and DNA decreased in all patients during therapy and 6 patients lost HBeAg. Five developed anti-HBe and 1 lost HBsAg and developed anti-HBs. No such changes occurred in the untreated control group over the 18-month period of observation. A 1-month course of ARA-AMP inhibits productive HBV replication and in some patients this is associated with a later loss of HBeAg and development of anti-HBe. However, intercurrent infection occurred in 3 of the treated patients with other hepatotrophic viruses known to inhibit HBV replication.

2000 persons in the UK were examined serologically for antibodies to human T-lymphotropic virus type III (HTLV-III). Sera reacting in a membrane immunofluorescence assay (IFA) to HTLV-III were also positive when tested against cells infected with lymphadenopathy virus (LAV-1), and cross-adsorption tests indicated that these retroviruses are probably identical. A competitive radioimmunoassay (RIA), which was wholly concordant with IFA, was used to screen the sera. 30/31 patients with the acquired immunodeficiency syndrome (AIDS) were seropositive, as were 89% patients with persistent generalised lymphadenopathy (PGL), 17% symptomless homosexual men, 34% haemophiliacs receiving pooled clotting factors, and 1.5% intravenous drug abusers. None of more than 1000 unselected blood donors was seropositive. These data confirm the close association between HTLV-III and AIDS and PGL and show that infection with HTLV-III is also prevalent in the populations in whom these syndromes are most likely to develop. However, it would be unwise to presume that AIDS will necessarily develop in seropositive subjects.

The future design of controlled trials of antiviral therapy which might include homosexual hepatitis B virus (HBV) carriers requires base-line data on the spontaneous rate of loss of HBeAg and the prevalence of human T-lymphotropic virus III (HTLV-III/LAV) infection. Fifty-one untreated HBsAg and HBeAg-positive homosexual HBV carriers were followed for a median HBeAg-positive time of 23.5 months (range 6-85.5). Ten lost HBeAg, giving an annual rate of spontaneous loss of HBeAg of 10%. This rate is considerably higher than the apparent rate in a previous report and has considerable implications for the interpretation of previous, and the design of future, controlled trials in this population. A rapid rise in the prevalence of anti-HTLV-III/LAV amongst HBV carriers was demonstrated from 1981 such that by 1984 over 60% of HBV carriers were anti-HTLV-III-positive. HBV-DNA polymerase levels were not significantly different in asymptomatic anti-HTLV-III/LAV-positive compared to anti-HTLV-III/LAV-negative HBV carriers. Nevertheless, since chronic HTLV-III/LAV infection in its later stages may potentiate HBV replication, it is a factor that will need to be considered together with many others in any trial stratification procedure.