Genital tract infections among HIV-infected pregnant women in Malawi, Tanzania and Zambia.

SUMMARY: The aim of this study was to compare the prevalence and factors associated with genital tract infections among HIV-infected pregnant women from African sites. Participants were recruited from Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. Genital tract infections were assessed at baseline. Of 2627 eligible women enrolled, 2292 were HIV-infected. Of these, 47.8% had bacterial vaginosis (BV), 22.4% had vaginal candidiasis, 18.8% had trichomoniasis, 8.5% had genital warts, 2.6% had chlamydia infection, 2.2% had genital ulcers and 1.7% had gonorrhoea. The main factors associated with genital tract infections included genital warts (adjusted odds ratio [AOR] 1.8, 95% CI 1.2-2.7), genital ulcers (AOR 2.4, 95% CI 1.2-5.1) and abnormal vaginal discharge (AOR 2.5, 95% CI 1.9-3.3) for trichomoniasis. BV was the most common genital tract infection followed by candidiasis and trichomoniasis. Differences in burdens and risk factors call for enhanced interventions for identification of genital tract infections among HIV-infected women.

Predictors of mortality in HIV-1 exposed uninfected post-neonatal infants at the Kenyatta National Hospital, Nairobi.

OBJECTIVES: To identify potential predictors of mortality, to determine mortality rate and to identify prevalent causes of death in a cohort of HIV-1 exposed uninfected infants. DESIGN: Prospective cohort study. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Three hundred and fifty one HIV-1 exposed uninfected post-neonatal infants who survived to one year of age. RESULTS: Sixteen infants died (post-neonatal mortality rate of 47/1000 live births), 14 (88%) before six months of age. The most frequently identified medical conditions at death included bronchopneumonia, diarrhoea and failure to thrive. In multivariate analysis, prematurity (RR=10.5, 95%CI 3.8-29.1, p<0.001), teenage motherhood (RR=3.6, Cl 1.0-13.2, p=0.05) and symptomatic maternal HIV-1 disease (RR=2.7, CI 0.9-7.7, p=0.06) were associated with infant mortality. CONCLUSION: Prematurity, teenage motherhood and symptomatic HIV-1 maternal disease were important predictors for post-neonatal mortality in this cohort of HIV-1 exposed uninfected infants. These factors should be considered in monitoring and follow up in prevention of mother-to-child HIV-1 transmission (PMTCT) programs.

Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012.

We compared nevirapine (NVP) resistance (NVPR) mutations in maternal plasma 7 days vs. 6-8 weeks after single-dose NVP prophylaxis. In the HIVNET 012 trial, Ugandan women received a single dose of NVP in labor for prevention of HIV-1 mother-to-child transmission. NVPR mutations were detected in 70 (25%) of 279 women 6-8 weeks after NVP. Samples collected 7 days after NVP were analyzed from a subset of those 279 women. Genotyping was performed with the ViroSeq HIV-1 Genotyping System. NVPR was analyzed using paired samples from 7 days and 6-8 weeks after NVP. Sixty-five women had genotyping results obtained for samples collected at both 7 days and 6-8 weeks post-NVP. Twenty-one (32%) of those women had NVPR mutations detected in one or both samples. This included three women with NVPR at 7 days only, seven with NVPR at 6-8 weeks only, and 11 with NVPR at both time points. Eight women had >1 NVPR mutation detected 7 days after NVP. Y181C was the most common NVPR mutation detected at 7 days, whereas K103N was the most common NVPR mutation detected at 6-8 weeks. We conclude that NVPR may be detected in women as early as 7 days after single-dose NVP. Complex patterns of NVPR are detected in some women. The Y181C NVPR mutation often fades from detection by 6-8 weeks. In contrast, the K103N mutation emerges more slowly, but often remains detectable 6-8 weeks after NVP.

Morbidity and mortality in breastfed and formula-fed infants of HIV-1-infected women: A randomized clinical trial.

CONTEXT: Breastfeeding among women infected with human immunodeficiency virus type 1 (HIV-1) is associated with substantial risk of HIV-1 transmission, but little is known about the morbidity risks associated with formula feeding in infants of HIV-1-infected women in resource-poor settings. OBJECTIVE: To compare morbidity, nutritional status, mortality adjusted for HIV-1 status, and cause of death among formula-fed and breastfed infants of HIV-1-infected women. DESIGN: Randomized clinical trial conducted between 1992 and 1998. SETTING: Four antenatal clinics in Nairobi, Kenya. PARTICIPANTS: Of 401 live-born, singleton, or first-born twin infants of randomized HIV-1-seropositive mothers, 371 were included in the analysis of morbidity and mortality. INTERVENTIONS: Mothers were randomly assigned either to use formula (n = 186) or to breastfeed (n = 185) their infants. MAIN OUTCOME MEASURES: Mortality rates, adjusted for HIV-1 infection status; morbidity; and nutritional status during the first 2 years of life. RESULTS: Two-year estimated mortality rates among infants were similar in the formula-feeding and breastfeeding arms (20.0% vs 24.4%; hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.5-1.3), even after adjusting for HIV-1 infection status (HR, 1.1; 95% CI, 0.7-1.7). Infection with HIV-1 was associated with a 9.0-fold increased mortality risk (95% CI, 5.3-15.3). The incidence of diarrhea during the 2 years of follow-up was similar in formula and breastfeeding arms (155 vs 149 per 100 person-years, respectively). The incidence of pneumonia was identical in the 2 groups (62 per 100 person-years), and there were no significant differences in incidence of other recorded illnesses. Infants in the breastfeeding arm tended to have better nutritional status, significantly so during the first 6 months of life. CONCLUSIONS: In this randomized clinical trial, infants assigned to be formula fed or breastfed had similar mortality rates and incidence of diarrhea and pneumonia during the first 2 years of life. However, HIV-1-free survival at 2 years was significantly higher in the formula arm. With appropriate education and access to clean water, formula feeding can be a safe alternative to breastfeeding for infants of HIV-1-infected mothers in a resource-poor setting.

Effect of breastfeeding on mortality among HIV-1 infected women: a randomised trial.

BACKGROUND: We have completed a randomised clinical trial of breastfeeding and formula feeding to identify the frequency of breastmilk transmission of HIV-1 to infants. However, we also analysed data from this trial to examine the effect of breastfeeding on maternal death rates during 2 years after delivery. We report our findings from this secondary analysis. METHODS: Pregnant women attending four Nairobi city council clinics were offered HIVtests. At about 32 weeks' gestation, 425 HIV-1 seropositive women were randomly allocated to either breastfeed or formula feed their infants. After delivery, mother-infant pairs were followed up monthly during the first year and quarterly during the second year until death, or 2 years after delivery, or end of study. FINDINGS: Mortality among mothers was higher in the breastfeeding group than in the formula group (18 vs 6 deaths, log rank test, p=0.009). The cumulative probability of maternal death at 24 months after delivery was 10.5% in the breastfeeding group and 3.8% in the formula group (p=0.02). The relative risk of death for breastfeeding mothers versus formula feeding mothers was 3.2 (95% CI 1.3-8.1, p=0.01). The attributable risk of maternal death due to breastfeeding was 69%. There was an association between maternal death and subsequent infant death, even after infant HIV-1 infection status was controlled for (relative risk 7.9, 95% CI 3.3-18.6, p<0.001). INTERPRETATION: Our findings suggest that breastfeeding by HIV-1 infected women might result in adverse outcomes for both mother and infant.

Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections.

To determine the effects of plasma, genital, and breast milk human immunodeficiency virus type 1 (HIV-1) and breast infections on perinatal HIV-1 transmission, a nested case-control study was conducted within a randomized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi, Kenya. In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years, maternal viral RNA levels >43,000 copies/mL (cohort median) were associated with a 4-fold increase in risk of transmission (95% confidence interval [CI], 2.2-7.2). Maternal cervical HIV-1 DNA (odds ratio [OR], 2.4; 95% CI, 1.3-4.4), vaginal HIV-1 DNA (OR, 2.3; 95% CI, 1.1-4.7), and cervical or vaginal ulcers (OR, 2.7; 95% CI, 1.2-5.8) were significantly associated with infant infection, independent of plasma virus load. Breast-feeding (OR, 1.7; 95% CI, 1.0-2.9) and mastitis (relative risk [RR], 3.9; 95% CI, 1.2-12.7) were associated with increased transmission overall, and mastitis (RR, 21.8; 95% CI, 2.3-211.0) and breast abscess (RR, 51.6; 95% CI, 4.7-571.0) were associated with late transmission (occurring >2 months postpartum). Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions.

Anal sex among HIV-seronegative women at high risk of HIV exposure. The HIVNET Vaccine Preparedness Study 2 Protocol Team.

To assess the prevalence and the sociodemographic and behavioral correlates of anal sex in a cohort of HIV-seronegative U.S. women at high risk of HIV exposure, we administered a risk assessment using audio computer-assisted self-interview (A-CASI). Of 1268 sexually active women, 432 (32%) reported anal sex in the previous 6 months. Compared with women who did not report anal sex, those who did had more unprotected vaginal sex (median of 11 versus 7 episodes; p <. 001) and a higher proportion of unprotected sexual (vaginal plus anal) episodes (median of 0.90 versus 0.81; p =.01). Anal sex was reported by higher proportions of women who did not always use condoms, who used crack in the past year, who were

Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial.

CONTEXT: Transmission of human immunodeficiency virus type 1 (HIV-1) is known to occur through breastfeeding, but the magnitude of risk has not been precisely defined. Whether breast milk HIV-1 transmission risk exceeds the potential risk of formula-associated diarrheal mortality in developing countries is unknown. OBJECTIVES: To determine the frequency of breast milk transmission of HIV-1 and to compare mortality rates and HIV-1-free survival in breastfed and formula-fed infants. DESIGN AND SETTING: Randomized clinical trial conducted from November 1992 to July 1998 in antenatal clinics in Nairobi, Kenya, with a median follow-up period of 24 months. PARTICIPANTS: Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial end points. INTERVENTIONS: Mother-infant pairs were randomized to breastfeeding (n = 212) vs formula feeding arms (n = 213). MAIN OUTCOME MEASURES: Infant HIV-1 infection and death during the first 2 years of life, compared between the 2 intervention groups. RESULTS: Compliance with the assigned feeding modality was 96% in the breastfeeding arm and 70% in the formula arm (P<.001). Median duration of breastfeeding was 17 months. Of the 401 infants included in the analysis, 94% were followed up to HIV-1 infection or mortality end points: 83% for the HIV-1 infection end point and 93% to the mortality end point. The cumulative probability of HIV-1 infection at 24 months was 36.7% (95% confidence interval [CI], 29.4%-44.0%) in the breastfeeding arm and 20.5% (95% CI, 14.0%-27.0%) in the formula arm (P = .001). The estimated rate of breast milk transmission was 16.2% (95% CI, 6.5%-25.9%). Forty-four percent of HIV-1 infection in the breastfeeding arm was attributable to breast milk. Most breast milk transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months, although transmission continued throughout the duration of exposure. The 2-year mortality rates in both arms were similar (breastfeeding arm, 24.4% [95% CI, 18.2%-30.7%] vs formula feeding arm, 20.0% [95% CI, 14.4%-25.6%]; P = .30). The rate of HIV-1-free survival at 2 years was significantly lower in the breastfeeding arm than in the formula feeding arm (58.0% vs 70.0%, respectively; P = .02). CONCLUSIONS: The frequency of breast milk transmission of HIV-1 was 16.2% in this randomized clinical trial, and the majority of infections occurred early during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1-free survival.

Use of nonoxynol-9 and changes in vaginal lactobacilli.

Several in vitro studies have shown nonoxynol-9 (N-9) to be toxic to lactobacilli, especially to strains that produce H2O2. Data from a randomized, double-blind, placebo-controlled crossover trial that investigated the safety and toxicity of 2 weeks of daily vaginal application of an N-9 gel were analyzed, to examine the effect of N-9 use on vaginal lactobacilli and bacterial vaginosis. In vivo, N-9 promoted sustained colonization by H2O2-producing lactobacilli among women already colonized (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2-2.7). In addition, use of N-9 for 2 weeks reduced the likelihood of bacterial vaginosis (RR, 0.5; 95% CI, 0.3-1.0). In contrast, N-9 use by women initially colonized only by non-H2O2-producing lactobacilli resulted in loss of vaginal lactobacilli (RR, 2.5; 95% CI, 1.2-5.3). These data suggest that daily use of N-9 does not adversely affect vaginal colonization by H2O2-producing lactobacilli but that such use may promote loss of non-H2O2-producing strains.

Pattern of bacterial infections and antimicrobial susceptibility at the Kenyatta National Hospital, Nairobi, Kenya.

To monitor clinically significant isolates and their antimicrobial susceptibilities, all specimens sent to microbiology laboratory of the Kenyatta National Hospital were cultured on appropriate media. The susceptibility of the isolates was performed on Muller Hinton or diagnostic sensitivity test (DST) agar using comparative discs diffusion technique. The results were then entered into Microbe Base 2 computer programme. A total of 7416 clinically significant isolates were collected from 1991 to 1995. The most commonly isolated organisms were E.coli, Klebsiella and Staphylococcus aureus. Most of these hospital acquired infections had multiple resistance to conventional antimicrobials, namely, penicillin, tetracyclines, gentamicin, trimethoprim/sulphamethoxazole and ampicillin. The resistance pattern was high among both gram negative and positive bacteria isolates. Beta-lactamase production amongst them were 51%, 69.3%, 79.6% respectively. Prevalence of methicillin resistant Staphylococcus aureus was 39.8%. Addition of clavulanic acid to amoxycillin increased Staphylococcus aureus susceptibility three fold. The emergence of multiple drug resistance calls for a continuous monitoring and reviewing of antibiotic policy in the hospital and the country at large.

Community acquired bacterial infections and their antimicrobial susceptibility in Nairobi, Kenya.

The purpose of the study was to determine the pattern and antimicrobial sensitivity on community acquired bacterial strains in Nairobi, Kenya. Clinical specimens collected from out-patient clinics at the Kenyatta National Hospital were cultured on appropriate media and identified according to Cowen and Steel's manual. The antimicrobial sensitivity was determined using comparative disc diffusion techniques. Between 1991 and 1995, there were a total of 1659 positive cultures comprising 30 different bacterial species. Out of the overall gram negative isolates (61.9%), E.coli and Klebsiella spp formed over 70%. Among the gram positive, Staphylococcus aureus, Enterococcus and coagulase negative staphylococcus spp constituting 41%, 26% and 18% respectively were the most common. Most organisms showed multiple resistance patterns to commonly used antimicrobials similar to hospital acquired infections. The gram negative isolates were resistant to cotrimoxazole, ampicillin, tetracyclines, chloramphenicol, and sulphamethoxazole. However, the sensitivity of these organisms to gentamicin and kanamycin was between 60 and 90%. Among the gram positive isolates, there was a high resistance to penicillin and tetracyclines (60-90%) while the resistance to lincomycin, minocycline and chloramphenicol was low (5-50%). All isolates were, however, highly sensitive to cephalosporins and fluoroquinolones. Beta-lactamase production among, E.coli, Klebsiella spp and Staphylococcus aureus was 48.9%, 76.7%, 76.1% respectively. Methicillin resistance for Staphylococcus aureus was 59.2%. Indiscriminate use of antibiotics in the community may have selected for resistant strains. This calls for urgent need to review policies on prescription practices.

Genital ulcer disease among STD clinic attenders in Nairobi: association with HIV-1 and circumcision status.

In previous studies, genital ulcers in men have been found to be associated with increased risk of HIV-1 seroconversion. To further explore this association male patients attending a sexually transmitted disease (STD) clinic in Nairobi for either urethritis (controls, n = 276) or a genital ulcer (cases, n = 607) were compared with respect to sexual behaviour, presence of HIV-1 antibody and circumcision status. Patients were followed to study risk factors for incident genital ulcers and HIV-1 seroconversion. At entry, being married was associated with higher prevalence of HIV-1 (OR = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.23). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. It is argued that the association between genital ulcers and HIV-1 infection may be more complex than ulcers simply being a risk factor for HIV-1 infection, and that HIV-1 infection may either increase the risk of acquiring a genital ulcer, or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

PIP: Male patients (mean age, 28 years) attending a sexually transmitted disease clinic in Nairobi, Kenya, for either urethritis (276 controls) or a genital ulcer (607 cases) were compared with respect to sexual behavior, presence of HIV-1 antibody, and circumcision status. Only 164 men were not circumcised. Circumcised men reported more life-time sex partners than uncircumcised men (19 vs. 10, p 0.01). Patients were followed up for 196 days to explore the risk factors for incident genital ulcers and HIV-1 seroconversion. On average, 2.66 follow-up visits per patient were recorded. 28 men seroconverted to HIV-1 during follow-up. 61% of the ulcer patients reported sex workers as the likely source of their infection, whereas 58% of the urethritis patients did so. Multiple logistic regression variables of marital status, age, and genital ulcer in the past were used to examine the relationship among these variables. Ulcer in the past was a significant predictor of a current ulcer (p 0.01) and higher age was significantly associated with HIV-1 seropositivity (p 0.01). At entry, being married was associated with higher prevalence of HIV-1 (odds ratio [OR] = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.3). 68 men acquired a new ulcer during follow-up. HIV-1 seropositivity at enrolment was significantly associated with genital ulcer reinfection (relative risk = 3.63 by Cox's regression). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. The association between genital ulcers and HIV-1 infection may be more complex than ulcers' simply being a risk factor for HIV-1 infection: either HIV-1 infection may increase the risk of acquiring a genital ulcer or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

Comparison of the declines in CD4 counts in HIV-1-seropositive female sex workers and women from the general population in Nairobi, Kenya.

Studies from Kenya have reported rapid clinical disease progression among HIV-infected professional sex workers. The reasons for this rapid decline are unknown. To better understand factors influencing the course of disease, HIV-1 disease progression was explored in terms of declines in CD4 counts. Two samples from Nairobi, Kenya, were studied, one from a cohort of female sex workers and another, as a comparison group, from mothers enrolled in an HIV-1 vertical-transmission study. A Markov model was used to analyze transitions between HIV-1 disease stages as defined by CD4 counts. It appears that sex workers experience a rapid decline in CD4 counts, consistent with earlier findings of rapid clinical disease progression among individuals in this group. The rate of decline in CD4 counts among the mothers appears to be lower. It is speculated that either intensive exposure to sexually transmitted pathogens or infection with several strains of HIV-1 may account for the rapid disease progression among female sex workers.

Low dose erythromycin regimen for the treatment of chancroid.

Haemophilus ducreyi is the commonest cause of genital ulcer disease in Africa and is associated with heterosexual transmission of human immunodeficiency virus(HIV). The World Health Organization currently recommends erythromycin 500 mg three times a day for seven days as the treatment of choice for Haemophilus ducreyi infection. We studied the effectiveness of a lower dose erythromycin treatment regime, 250 mg three times a day for seven days in the treatment of chancroid. Patients with genital ulcer disease presenting at Nairobi City council clinic between January and March, 1992 were recruited into the study. Swabs were taken from the ulcers for Haemophilus ducreyi and venous blood was screened for syphilis and HIV antibodies. A total of 219 patients were enrolled for the study and were reviewed on days seven and fourteen for side effects, bacteriological and clinical cure rates. 26.4% of the study population were HIV-1 seropositive. The treatment regime was well tolerated and effective in both HIV seropositive and seronegative patients. Complete bacteriological cure rate was achieved in Haemophilus ducreyi culture positives by day seven irrespective of the HIV serostatus. However, the clinical cure rate for HIV seropositive patients was 88% compared to 99% for seronegative patients (p<.001). It is concluded that a low dose erythromycin is an inexpensive and effective treatment for chancroid with complete bacteriological cure rate, although the healing process takes longer in HIV seropositive patients.