Pa Tamba Ngom

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.

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.

Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa.

ObjectiveTo examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death. DesignRetrospective analysis of HIV-2 cohort subjects. MethodsFifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used. ResultsThe mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10 RNA copies/ml [95% confidence interval (CI), 0.81–2.7;P = 0.0006;r = 0.46; n = 52] and 1.76 CD4% faster for every increase in log10 DNA copies/105 PBMC (95% CI 0.46–3.1;P = 0.01;r = 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P = 0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10 increase in RNA load (95% CI, 1.3–3.5;P = 0.0023) but only by 1.09 for each log10 increase in DNA load (95% CI, 0.64–1.87;P = 0.8). ConclusionThis longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.

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.

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.

Evaluation of T cell subsets by an immunocytochemical method compared to flow cytometry in four countries

The authors tested an alternative method for CD4 and CD8 T lymphocytes enumeration, the immunoalkaline phosphatase method (IA), in three African countries and in Denmark. The IA determinations from 136 HIV antibody positive and 105 HIV antibody negative individuals were compared to the corresponding results obtained by flow cytometry (FC) performed in the respective countries. The authors found good correspondence between the two methods for measurements of CD4 and CD8 T lymphocytes independent of serological status and geographical site. However, the CD4 and CD8 T lymphocyte values obtained by the two methods are not interchangeable as IA compared to FC consistently gives higher percentage of CD4 T lymphocytes, and lower percentages of CD8 T lymphocytes. Mean differences between the two methods did not differ between the three African countries indicating that the IA method provides systematic results. Replicate measurements suggested good correspondence between results obtained by IA. By using an IA level of < 300 CD4 T lymphocytes/μl, the sensitivity was 81% and specificity 96% for detecting an FC level of < 200 CD4 T lymphocytes/μl. Using an IA level of < 20% CD4 T lymphocytes, the sensitivity was 89% and specificity 95% for detecting an FC level of <14% CD4 T lymphocytes, The FC and IA methods had the same internal correspondence between low absolute CD4 T cell counts and low CD4 percentages; the sensitivity and specificity for detecting a low absolute CD4 T cell count with a low CD4 percentage was 92% and 68% for FC and 91% and 73% for IA, respectively. The IA method is 10‐fold cheaper than FC, is independent of advanced laboratory facilities, and does not need immediate processing of samples as blood smears can be stored for long periods. The IA method is therefore suitable for use in areas with limited resources and laboratory facilities where there is a need for immunological surveillance in hospital or community studies.