HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis

In their response to our report1Sewankambo N Gray RH Wawer MJ et al.HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 546-550Summary Full Text Full Text PDF PubMed Scopus (541) Google Scholar of an association between prevalent HIV infection and depletion of vaginal lactobacilli in Uganda, Austin Ugwumadu and colleagues (Oct 25, p 1251)2Ugwumadu A Hay P Taylor-Robinson D HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 1251Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar question whether the association between bacterial vaginosis and HIV may be confounded by concurrent cervical infections, particularly Chlamydia trachomatis. As noted in table 3 in our report, most women had no evidence of cervical infections, and no association was found between prevalent HIV and chlamydial infection, irrespective of the presence of bacterial vaginosis. Ugwumadu et al also comment on the low prevalence of C trachomatis in this population and question whether this may be due to a reduced sensitivity of the urinary ligase chain reaction (LCR) assay as a consequence of difficulties in specimen handlingWe have compared LCR detection of C trachomatis in urine samples with hybrid capture detection of C trachomatis from 905 self-collected vaginal swab specimens (Digene, Silver Spring, MD), and found complete agreement between the two assays and modes of sample collection. The prevalence of C trachomatis in this unselected and largely symptom-free sample of rural Ugandan women is not atypical for other unselected populations in rural East Africa (J Schachter, personal communication), and the age-specific prevalence of chlamydia shows the expected higher rates in younger women (at ages 15–19 years, the prevalence of C trachomatis was 6·6%). Further-more, recent studies have shown stability of LCR detection of C trachomatis in urine kept at room temperature for up to 72 h before processing. We are therefore confident that the urinary LCR assay is sensitive for the detection of C trachomatis in the Rakai setting.S Ledru and colleagues (Oct 25, p 1251)3Ledru S Meda N Ledru E Bazie AJ Chiron JP HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 1251-1252Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar question our use of morphological methods for diagnosis of bacterial vaginitis and recommend the use of clinical criteria. As we noted the morphological assessment of this condition has been validated in studies of conventional clinical diagnostic criteria. Moreover, in collaboration with other investigators, we have examined the association between prevalent HIV and clinically diagnosed bacterial vaginosis among 6667 pregnant women from Blantyre, Malawi.4Taha TE, Miotti P, Dalabetta G, et al. Bacterial vaginosis during pregnancy: associations with HIV, preterm delivery and mother-to-child transmission of HIV. Presented at conference on global strategies for the prevention of HIV transmission from mothers to infants. Washington DC, Sept 3–6, 1997: 13.Google Scholar, 5Gray RH Wawer MJ Taha TE et al.Depleted vaginal Lactobacilli and BV increase HIV acquisition in studies in Uganda and Malawi. International Infectious Disease Society of America, San FranciscoSept 13–16 1997Google Scholar In the Malawian study, the multivariate adjusted odds ratio of HIV infection in women with clinical bacterial vaginosis was 2·5 (95% CI 2·1–2·9),4Taha TE, Miotti P, Dalabetta G, et al. Bacterial vaginosis during pregnancy: associations with HIV, preterm delivery and mother-to-child transmission of HIV. Presented at conference on global strategies for the prevention of HIV transmission from mothers to infants. Washington DC, Sept 3–6, 1997: 13.Google Scholar whereas in our Ugandan study, the odds ratio was 1·56 (1·24–1·97) with morphologically diagnosed and 2·08 (1·48–2·94) for severe infection (scores 9–10). Thus, the morphological diagnosis seems conservative.We have also analysed preliminary data on bacterial vaginosis and incident HIV infection with a nested case-control design. There were 77 incident cases of HIV who were individually matched by age (within 2·5 years) and place of residence, with 328 HIV-negative controls. The duration of observation was similar for cases and controls. These women provided a self-collected vaginal swab at the study visit before the follow-up interval during which they were at risk of seroconversion. Swabs were rolled onto microscope slides, gram-stained, and sent to the University of Pittsburgh for morphological evaluation, blinded with respect to HIV status. The findings suggest a possible increased risk of incident HIV infection associated with pre-existing bacterial infection with conditional logistic regression for matched data, the odds ratio of incident HIV was 1·50 (0·78–2·80). Although not significant, this result is consistent with the findings for HIV among women with bacterial vaginosis,1Sewankambo N Gray RH Wawer MJ et al.HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 546-550Summary Full Text Full Text PDF PubMed Scopus (541) Google Scholar, 4Taha TE, Miotti P, Dalabetta G, et al. Bacterial vaginosis during pregnancy: associations with HIV, preterm delivery and mother-to-child transmission of HIV. Presented at conference on global strategies for the prevention of HIV transmission from mothers to infants. Washington DC, Sept 3–6, 1997: 13.Google Scholar, 5Gray RH Wawer MJ Taha TE et al.Depleted vaginal Lactobacilli and BV increase HIV acquisition in studies in Uganda and Malawi. International Infectious Disease Society of America, San FranciscoSept 13–16 1997Google Scholar and suggests that depletion of vaginal lactobacilli may be a risk factor for HIV acquisition.We thank L Rabe for technical assistance. In their response to our report1Sewankambo N Gray RH Wawer MJ et al.HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 546-550Summary Full Text Full Text PDF PubMed Scopus (541) Google Scholar of an association between prevalent HIV infection and depletion of vaginal lactobacilli in Uganda, Austin Ugwumadu and colleagues (Oct 25, p 1251)2Ugwumadu A Hay P Taylor-Robinson D HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 1251Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar question whether the association between bacterial vaginosis and HIV may be confounded by concurrent cervical infections, particularly Chlamydia trachomatis. As noted in table 3 in our report, most women had no evidence of cervical infections, and no association was found between prevalent HIV and chlamydial infection, irrespective of the presence of bacterial vaginosis. Ugwumadu et al also comment on the low prevalence of C trachomatis in this population and question whether this may be due to a reduced sensitivity of the urinary ligase chain reaction (LCR) assay as a consequence of difficulties in specimen handling We have compared LCR detection of C trachomatis in urine samples with hybrid capture detection of C trachomatis from 905 self-collected vaginal swab specimens (Digene, Silver Spring, MD), and found complete agreement between the two assays and modes of sample collection. The prevalence of C trachomatis in this unselected and largely symptom-free sample of rural Ugandan women is not atypical for other unselected populations in rural East Africa (J Schachter, personal communication), and the age-specific prevalence of chlamydia shows the expected higher rates in younger women (at ages 15–19 years, the prevalence of C trachomatis was 6·6%). Further-more, recent studies have shown stability of LCR detection of C trachomatis in urine kept at room temperature for up to 72 h before processing. We are therefore confident that the urinary LCR assay is sensitive for the detection of C trachomatis in the Rakai setting. S Ledru and colleagues (Oct 25, p 1251)3Ledru S Meda N Ledru E Bazie AJ Chiron JP HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 1251-1252Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar question our use of morphological methods for diagnosis of bacterial vaginitis and recommend the use of clinical criteria. As we noted the morphological assessment of this condition has been validated in studies of conventional clinical diagnostic criteria. Moreover, in collaboration with other investigators, we have examined the association between prevalent HIV and clinically diagnosed bacterial vaginosis among 6667 pregnant women from Blantyre, Malawi.4Taha TE, Miotti P, Dalabetta G, et al. Bacterial vaginosis during pregnancy: associations with HIV, preterm delivery and mother-to-child transmission of HIV. Presented at conference on global strategies for the prevention of HIV transmission from mothers to infants. Washington DC, Sept 3–6, 1997: 13.Google Scholar, 5Gray RH Wawer MJ Taha TE et al.Depleted vaginal Lactobacilli and BV increase HIV acquisition in studies in Uganda and Malawi. International Infectious Disease Society of America, San FranciscoSept 13–16 1997Google Scholar In the Malawian study, the multivariate adjusted odds ratio of HIV infection in women with clinical bacterial vaginosis was 2·5 (95% CI 2·1–2·9),4Taha TE, Miotti P, Dalabetta G, et al. Bacterial vaginosis during pregnancy: associations with HIV, preterm delivery and mother-to-child transmission of HIV. Presented at conference on global strategies for the prevention of HIV transmission from mothers to infants. Washington DC, Sept 3–6, 1997: 13.Google Scholar whereas in our Ugandan study, the odds ratio was 1·56 (1·24–1·97) with morphologically diagnosed and 2·08 (1·48–2·94) for severe infection (scores 9–10). Thus, the morphological diagnosis seems conservative. We have also analysed preliminary data on bacterial vaginosis and incident HIV infection with a nested case-control design. There were 77 incident cases of HIV who were individually matched by age (within 2·5 years) and place of residence, with 328 HIV-negative controls. The duration of observation was similar for cases and controls. These women provided a self-collected vaginal swab at the study visit before the follow-up interval during which they were at risk of seroconversion. Swabs were rolled onto microscope slides, gram-stained, and sent to the University of Pittsburgh for morphological evaluation, blinded with respect to HIV status. The findings suggest a possible increased risk of incident HIV infection associated with pre-existing bacterial infection with conditional logistic regression for matched data, the odds ratio of incident HIV was 1·50 (0·78–2·80). Although not significant, this result is consistent with the findings for HIV among women with bacterial vaginosis,1Sewankambo N Gray RH Wawer MJ et al.HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.Lancet. 1997; 350: 546-550Summary Full Text Full Text PDF PubMed Scopus (541) Google Scholar, 4Taha TE, Miotti P, Dalabetta G, et al. Bacterial vaginosis during pregnancy: associations with HIV, preterm delivery and mother-to-child transmission of HIV. Presented at conference on global strategies for the prevention of HIV transmission from mothers to infants. Washington DC, Sept 3–6, 1997: 13.Google Scholar, 5Gray RH Wawer MJ Taha TE et al.Depleted vaginal Lactobacilli and BV increase HIV acquisition in studies in Uganda and Malawi. International Infectious Disease Society of America, San FranciscoSept 13–16 1997Google Scholar and suggests that depletion of vaginal lactobacilli may be a risk factor for HIV acquisition. We thank L Rabe for technical assistance.