Andrew Wilkins

HIV-2-infected patients survive longer than HIV-1-infected patients

ObjectiveTo compare survival of patients infected with HIV-1 and HIV-2. DesignLongitudinal follow-up of 175 HIV-1-and 294 HIV-2-infected patients identified in, or referred to a hospital in The Gambia. MethodsSurvival analysis methods were used and the death rate ratios for HIV-2 relative to HIV-1 patients were estimated using proportional hazard regression models that allowed for age, sex and clinical or immunological features. ResultsThe overall death rate ratio for HIV-2 relative to HIV-1 was 0.67 [95% confidence interval (Cl), 0.49–0.91] when adjusted for age, sex and World Health Organization Bangui clinical classification. When allowing for age, sex and three strata of CD4+ count, the rate ratio was 0.64 (95% Cl, 0.43–0.94), and for three strata of β2-microglobulin levels 0.60 (95% Cl, 0.42–0.84). ConclusionMortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1-infected patients.

The epidemiology of HIV infection in a rural area of Guinea-Bissau.

ObjectivesTo determine the prevalence of HIV infection and its relationship to age, sex and other factors. Design and settingCross-sectional survey of a rural community in Guinea-Bissau. MethodsQuestionnaire-administration and screening of sera from subjects aged >m; 15 years. ResultsOf the 2770 subjects tested, 220 (7.9%) were HIV-2-seropositive, four (0.1%) were HIV-1-seropositive and 10 (0.4%) were dually reactive. Overall prevalence of HIV-2 was 9.3% in women, peaking at 17.2% in the 35–44 age group, and 6.6% in men, peaking at 19.1% in the 45–54 age group. The mean age of the four subjects with HIV-1 infection was 24 years, which was significantly lower than those with HIV-2 infection. HIV-2 infection was more prevalent among women who were widowed or divorced, women whose husbands were living away from the study area, and women who had lived in the capital, Bissau. The majority of subjects with an infected spouse remained uninfected and none of the women aged < 25 years whose husbands were infected were seropositive. The prevalence varied significantly between settlements within the study area. ConclusionsThe pattern of HIV-2 infection in this rural community has similarities to that found in urban Bissau, and prevalence in both areas peaks in older subjects than in HIV-1 foci. The findings support previous suggestions that HIV-2 is not a recent introduction to Guinea-Bissau, and that it is less pathogenic and less readily transmitted than HIV-1.

Prostitutes and their clients: A Gambian survey

The social backgrounds and working behaviour of 248 prostitutes in urban and rural areas of The Gambia were investigated. Prostitutes were found to be highly mobile, moving frequently between a number of working locations in The Gambia and neighbouring Senegal, from which most of them originated. The educational level of prostitutes and the standard of living of their natal families were above average. Prostitutes worked on average four days a week and had between two and three clients a night. Condoms were used in up to 80% of contacts. 795 clients of prostitutes were interviewed and found to be on average of low educational and occupational status. Half were non-Gambian and most were currently travelling or living away from home.

Rate of decline of percentage CD4+ cells is faster in HIV-1 than in HIV-2 infection

Increasing evidence suggests that the pathogenesis of HIV-1 is different from that of HIV-2. Thus, we have measured, longitudinally at various times over a median follow-up of 2.1 years, the percentage CD4+ cells of 94 patients infected with HIV-1 and 164 patients infected with HIV-2. The pattern of decline of CD4% over time was linear for patients with either infection. Multilevel statistical modeling techniques showed that after stratifying for HIV status, the rate of decline of CD4% was faster among patients who died than among those who survived (difference in rate of decline = 2.34% CD4+ cells/year; p = 0.0002). After stratifying for survival status, the rate of decline was faster and less variable among patients infected with HIV-1 than among patients infected with HIV-2 (difference in rate of decline = 1.12% CD4+ cells/year; p = 0.05). The proportion of patients who showed no fall in CD4+ cells was higher in HIV-2 than in HIV-1 infection (p = 0.026). These data suggest fundamental differences between the two infections, with HIV-1 being more pathogenic resulting in a faster and more homogeneous rate of decline than HIV-2. In HIV-2 infection, disease in many patients progresses slowly, but in some the advance is just as fast as that in HIV-1 infection. The reasons for this marked heterogeneity need elucidation to understand the disease and to target therapeutic interventions against HIV-2 in those most at risk.

Low level viremia and high CD4% predict normal survival in a cohort of HIV type-2-infected villagers

A community-based study of human immunodeficiency virus type 2 (HIV-2) infection was conducted in a rural village in northern Guinea Bissau, West Africa to assess the relationship between plasma HIV-2 RNA levels, CD4 lymphocyte percentage, and survival over an 8-year period. The cohort of 133 HIV-2-infected individuals and 160 HIV-uninfected controls enrolled in 1991 were followed up at home until 1998. Thirty-one (23%) HIV-2-infected and 24 (16%) HIV-uninfected individuals died over the follow-up period (mortality hazard ratio 1.7, 95% CI 1.0, 2.9; p= 0.06). In HIV-2-infected individuals, the median HIV-2 RNA level was 347 copies/ml and the mean CD4% was 28.6. Both plasma viremia and CD4% were independent predictors of survival, with hazard ratios increasing by 1.6 (95% CI, 1.1, 2.3) for each log(10) increase of plasma viremia and 1.7 (1.1, 2.6) for each 10% decrease of CD4%. Infected subjects with a plasma viral load >or= the median (347 copies/ml) and a CD4% <or= the mean (28.6%) had a mortality hazard ratio of 3.1 (95% CI 1.7, 5.8) compared to uninfected controls, whereas the remaining infected subjects had a mortality rate similar to uninfected controls, the mortality hazard ratio being 1.0 (95% CI, 0.5, 2.1.) In those who survived between 1991 and 1996, HIV-2 RNA levels were unchanged overall and CD4 lymphocyte counts remained high. In conclusion, baseline HIV-2 RNA levels predicted a normal survival for the majority, with low and stable levels of plasma viremia characterizing HIV-2 infections in this rural West African community.

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

ObjectivesTo determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. MethodsAll patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. ResultsKarnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were loge serum neopterin level, CD4 cell count and loge serum β2-microglobulin (β2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected patients were six (4–11) and 13 (9–20) months, respectively. These survival times do not differ significantly. ConclusionsThe Karnofsky score and measurements of serum neopterin or β2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.

Age of wife as a major determinant of male-to-female transmission of HIV-2 infection: a community study from rural West Africa.

Objective: To examine whether proviral load is important for transmission between spouses, since we have previously found that the proviral load of HIV‐2 predicts the severity of infection. Design: Proviral load was examined in 121 HIV‐2‐infected adults in a rural area of Guinea‐Bissau. For the 68 subjects who had a spouse of known HIV status the risk of the spouse being infected was examined. Methods: Statistical methods for dependent data were used, because several couples were polygamous. Results: Twenty‐seven HIV‐2‐infected men had 52 current wives of whom 17 (33%) were HIV‐2‐seropositive. Forty‐one HIV‐2‐infected women had 36 current husbands of known HIV serostatus; nine (25%) were HIV‐2‐positive. In univariate analyses, concordance of female partners of HIV‐2‐infected men increased with a previous history of prostitution, age of wife, lack of age difference between the spouses, number of previous husbands, number of wives of the man, and the proviral load. The only significant predictor of concordance in multivariate analyses when wives with a history of prostitution were excluded was an age of 45 years or older lodds ratio (OR), 8.68; 95% confidence interval (CI), 2.34–32.22. This tendency was not explained by the length of current marriage. Although husbands with a high proviral load were more likely to have concordant spouses than those with a low proviral load (< 20 copies/105 CD4 cells), this association was not statistically significant (OR, 2.59; 95% CI, 0.90–7.46). Among spouses of HIV‐2‐infected women, none of the examined factors, including previous prostitution or proviral load in the woman, predicted whether the husband was HIV‐2‐infected. Conclusions: Women appear to be more susceptible to HIV‐2 infection after 40–45 years of age. The apparent change in susceptibility may be a major reason for the distinctive age pattern of HIV‐2 infection observed in West Africa.

Maternal HIV-1 and HIV-2 infection and child survival in The Gambia.

ObjectiveTo compare the survival of children born to HIV-1 or HIV-2 seropositive mothers with that of children born to HIV-seronegative mothers and to evaluate risk factors for mortality. DesignPhysician-blinded prospective study. MethodsOne hundred and one HIV-1-seropositive, 243 HIV-2-seropositive pregnant women, and 468 HIV-seronegative women (control group) matched by age, parity, and health centre, were followed up in a study of mother-to-child transmission of HIV. Mothers and children were seen at 2 and 6 months of age and subsequently followed at 3-monthly intervals up to 18 months of age. HIV infection in children was diagnosed by polymerase chain reaction at 2, 9 or 18 months and by antibody assays at 18 months. ResultsFifteen per cent of children born to HIV-1-infected mothers died compared with 7% of children born to HIV-2-infected mothers [hazard ratio, 2.3; 95% confidence interval (CI), 1.1–4.7;P = 0.02], and 6% of HIV-seronegative mothers (hazard ratio, 2.6; 95% CI, 1.4–5.0;P = 0.003). Six of the 17 children known to be HIV-1 infected died compared with none among the eight HIV-2-infected children (P = 0.13). High proviral load in the babies, high antenatal maternal RNA plasma viral load, and maternal death increased child mortality significantly. ConclusionsMore children born to HIV-1-infected mothers died in comparison with those born to HIV-2-infected mothers or to mothers from the control group. This effect was due to excess death in HIV-1-infected infants which was associated with a high viral load in the affected mother and child.

The effects of post-test counselling on condom use among prostitutes in The Gambia

ObjectivesTo determine the effect of counselling on condom use by prostitutes. DesignCohort study. SettingField-based study in The Gambia. ParticipantsThirty-one (12 HIV-positive and 19 HIV-negative) prostitutes. InterventionsPost-test HIV counselling. Main outcome measuresLevels of condom use. ResultsOverall, counselling had no effect on condom use. ConclusionsScarce resources should be directed towards providing condoms in bars rather than counselling.

Immunological findings in African patients with pulmonary tuberculosis and HIV-2 infection

The prevalence of HIV-1 and HIV-2 infections in Africa has increased 2-3-fold in patients with pulmonary tuberculosis (PTB). Moreover 25-50% of patients with AIDS have active Mycobacterium tuberculosis infection. Since the majority of Africans are exposed to M. tuberculosis early in childhood it is believed that disease in HIV-seropositive patients is a result of reactivation of a latent infection due to immune damage by the virus. Our study of Gambian patients with PTB and HIV-2 infection supports this hypothesis and shows that the immune systems of HIV- seropositive patients with PTB is impaired but not always to the degree found in patients with AIDS. 7% of new patients attending tuberculosis clinics in the Gambia are infected with HIV but do not have AIDS as defined by the World Health Organization. Before treatment we selected 12 HIV-2-seropositive patients with sputum-positive PTB and matched them by age and extent of disease with 17 HIV-negative patients with PTB. The study also included 17 asymptomatic HIV-2 infected subjects without PTB 21 HIV-2 infected patients with AIDS and 84 HIV-negative controls selected from a sexually transmitted disease clinic. Subjects were considered HIV-2 infected if they were seropositive by a HIV-2 type-specific competitive enzyme-linked immunosorbent assay (ELISA; Wellcome Diagnostics Dartford England UK) and a type-specific Western blot (LAV2; Diagnostics Pasteur Marnes-la-Coquette France). Standard immunological tests included fluorescence-activated scanning for lymphocyte subset analyses and commercial radioimmunoassay tests to measure serum beta2-microglobulin (beta2M; Pharmacia Uppsala Sweden) and neopterin (Henning Berlin Germany) levels. Lymphocytes were cultured in the presence of 100 U/ml purified protein derivative (PPD; Evans Medical Horsham England UK). At 7 days proliferation was measured using a standard tritiated thymidine uptake assay and gamma-interferon production estimated in HIV-2 infection had lower CD4 cell counts and higher serum beta2M and neopterin levels than subjects in all other groups except those with AIDS. Despite the evident damage to the immune system responses to PPD were relatively well preserved in the majority of seropositive PTB patients. However 6 of the HIV-2 positive PTB patients had cell counts /1 4 of whom had negative skin tests. These criteria together with an opportunistic infection such as disseminated tuberculosis (which without lymph-node or liver biopsies is difficult to prove) are considered to be AIDS-defining. Our data support the hypothesis that PTB signals damage to the immune systems of HIV-infected patients without AIDS. Nevertheless these patients unlike those with AIDS may still have intact responses to TB antigens and most respond well to antituberculosis therapy. However a few such as those with a negative skin test to PPD may soon develop AIDS. (full text) (5 references cited in original document)