Risk of seropositivity to multiple oncogenic human papillomavirus types among human immunodeficiency virus-positive and -negative Ugandan women.

To understand the prospects for human papillomavirus (HPV) mass vaccination in the setting of a developing country, we studied the co-occurrence of seropositivity to multiple high-risk (hr) HPV types among HIV-positive and HIV-negative Ugandan women. Our seroepidemiological study was conducted among 2053 women attending antenatal clinics. Sera were analysed for antibodies to eight hrHPV types of the α-7 (18/45) and α-9 (16/31/33/35/52/58) species of HPV by using a multiplex serology assay. Our results show that seropositivity for greater than one hrHPV type was as common (18 %) as for a single type (18 %). HIV-positive women had higher HPV16, HPV18 and HPV45 seroprevalences than HIV-negative women. In multivariate logistic regression analysis, age (>30 years) and level of education (secondary school and above) reduced the risk, whereas parity (>5) and HIV-positivity increased the risk for multiple hrHPV seropositivity. However, in stepwise logistic regression analyses, HIV-status remained the only independent, stand-alone risk factor [odds ratio (OR) 1.7, 95 % confidence interval (CI) 1.0-2.8). On the other hand, the risk of HPV16 or HPV18 seropositive women, as compared to HPV16 or HPV18 seronegative women, for being seropositive to other hrHPV types was not significantly different when they were grouped by HIV-status (ORHPV16/HIV+ 12, 95 % CI 4.5-32 versus ORHPV16/HIV- 22, 95 % CI 15-31 and ORHPV18/HIV+ 58, 95 % CI 14-242 versus ORHPV18/HIV- 45, 95 % CI 31-65). In conclusion, seropositivity to HPV16, HPV18 and to non-vaccine hrHPV types is common in Ugandan women, suggesting that there is little natural cross-protective immunity between the types. HIV-positivity was an independent, stand-alone, albeit moderate risk factor for multiple hrHPV seropositivity. HPV mass vaccination may be the most appropriate method in the fight against cervical cancer in the Ugandan population.

The effect of tuberculin skin testing on viral load and anti-mycobacterial immune responses in HIV-1-infected Ugandan adults.

OBJECTIVE: To determine whether tuberculin skin testing (TST) is associated with an increase in human immunodeficiency virus (HIV) viral load, and to examine the effect of TST on anti-mycobacterial immune responses. DESIGN: A nested cohort study of HIV-1-infected adults. METHOD: Forty-two participants (21 TST-positive and 21 TST-negative) from a larger cohort were recruited to the study. Blood was collected for CD4+ T-cell count, whole blood was cultured, and plasma saved for viral load. These measurements were taken before, 3 days after, 3 months after, and 3 months plus 3 days after TST. Cytokine responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis and phytohaemagglutinin (PHA) were examined in the whole blood assay. RESULTS: Twenty-nine participants attended all four visits. No statistically significant change in viral load, CD4+ T-cell count, or cytokine response to PHA was observed at any visit. However, TST was associated with a transient increase in the interferon-gamma response to CFP and a lasting increase in the interleukin-5 response to CFP. CONCLUSION: There appeared to be a systemic effect of TST on the anti-tuberculosis immune response.

HIV-1-related pleural tuberculosis: elevated production of IFN-gamma, but failure of immunity to Mycobacterium tuberculosis.

BACKGROUND: Pleural tuberculosis can resolve spontaneously, suggesting that the inflammatory process may represent a protective immune response. However, pleural tuberculosis is strongly associated with HIV infection. It has been suggested that cell-mediated immune responses may be reduced, and direct bacterial invasion may have a role in pathogenesis, in HIV-positive cases. To test this hypothesis, we compared production of the pro-inflammatory cytokines, interferon (IFN)-gamma and tumour necrosis factor(TNF)-alpha, production of the immunosuppressive cytokine, interleukin (IL)-10, and mycobacterial culture positivity, in HIV-negative and HIV-positive patients with pleural tuberculosis. METHODS: Cytokine levels were measured in serum and pleural fluid, and in supernatants of blood and pleural fluid stimulated in vitro using mycobacterial antigens. Intracellular IFN-gamma and TNF-alpha production was measured after stimulation with phorbol myristate acetate and ionomycin in vitro. RESULTS: IFN-gamma was strikingly elevated in serum and pleural fluid in HIV-positive, compared to HIV-negative subjects (P < or = 0.02). TNF-alpha was elevated, but this was not statistically significant. IL-10 levels were higher in serum (P < 0.001), but similar in pleural fluid. IFN-gamma responses to soluble mycobacterial antigen in vitro were reduced in peripheral blood (P = 0.006), but not pleural fluid, of HIV-positive subjects. Intracellular cytokine staining suggested that CD8+ T cells were a major source of IFN-gamma in HIV-positive subjects. The proportion of subjects with a positive culture for Mycobacterium tuberculosis from pleural fluid was higher in the HIV-positive group. CONCLUSIONS: HIV-positive patients with pleural tuberculosis show elevated production of IFN-gamma, for which CD8+ T cells may be a major source. Mycobacterium tuberculosis can proliferate despite high levels of pro-inflammatory cytokines.