Paul J. Feldblum

SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria.

Background The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk. Methodology/Principal Findings This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1∶1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use. Conclusions/Significance SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY. Trial Registration ClinicalTrials.gov NCT00130078

Barrier contraceptive use and Hiv infection among high-risk women in Cameroon

ObjectivesTo measure the association between spermicide use and HIV infection, adjusting for condom use, and to measure the association between condom use and HIV infection, adjusting for spermicide use. DesignProspective study of women using nonoxynol-9 (N-9) spermicides and latex condoms, with up to 12 monthly clinic visits for interviews, examinations and tests, and re-supply. MethodsA total of 273 HIV-negative women with multiple sexual partners were enrolled, given latex condoms and N-9 vaginal spermicidal suppositories, and advised to use both every time they had sexual intercourse. Participants recorded data on sexual activity on pictorial coital logs. New HIV infections were detected and confirmed by quarterly enzyme-linked immunosorbent assays and Western blots, respectively. ResultsNineteen HIV infections occurred during mean follow-up of 8.1 months (an incidence rate of 10.4 infections per 100 woman-years). The adjusted HIV rate ratio (RR) was 0.1 [95% confidence interval (CI), 0.1–0.6] for more consistent compared with less consistent spermicide users; and 1.1 (95% Cl, 0.4–2.9) for more consistent compared with less consistent condom users. Among the subgroup of experienced condom users, the RR for more versus less consistent condom use was 0.3. ConclusionsThis is the first epidemiological evidence that N-9 spermicides can reduce the incidence of HIV infection. A more definitive randomized clinical trial is urgently needed.

Nonoxynol-9 use genital ulcers and HIV infection in a cohort of sex workers.

OBJECTIVES--To measure the associations between use of nonoxynol-9 (N-9) and incidence of genital ulcers, and incident ulcers and HIV seroconversion. METHODS--In a study of barrier contraceptive use and HIV infection, 273 female sex workers used condoms and 100 mg N-9 suppositories, and recorded sexual activity on coital logs. Genital ulcers were diagnosed clinically at monthly clinic visits. HIV infection was diagnosed by ELISA and Western blot. We calculated ulcer incidence rates by level of N-9 use. A nested matched case-control analysis assessed the effect of ulcers on HIV acquisition. RESULTS--More frequent N-9 use was not associated with genital ulcers and may have been protective against the lesions. Ulceration was not a strong risk factor for HIV acquisition in this study (odds ratio 1.1; 95% confidence interval 0.3-3.5). CONCLUSIONS--Frequent use of N-9 can cause genital irritation and ulceration. Ulcers, in turn, may be risk factors for HIV acquisition. This study, however, did not find an association between N-9 use and ulcers, nor between ulcers and HIV. There is probably a threshold of N-9 use frequency or dose below which the risk of ulceration is minimal. Ulcers due to infectious causes may have been prevented by N-9 use in this cohort.

Female condom introduction and sexually transmitted infection prevalence: results of a community intervention trial in Kenya.

ObjectiveTo measure the impact on sexually transmitted infection (STI) prevalence of a female condom introduction and risk-reduction program at Kenyan agricultural sites. DesignWe conducted a cluster-randomized trial to determine whether a replicable, community-level intervention would reduce STI prevalence. MethodsSix matched pairs of tea, coffee and flower plantations were identified. The six intervention sites received an information/motivation program with free distribution of female and male condoms, and six control sites received only male condoms and related information. Participants were tested for cervical gonorrhea and chlamydia by ligase chain reaction on urine specimens, and vaginal trichomoniasis by culture, at baseline, 6 and 12 months. ResultsParticipants at intervention (n = 969) and control sites (n = 960) were similar; baseline STI prevalence was 23.9%. Consistent male condom use was more than 20% at 12 months. Consistent female condom use was reported by 11 and 7% of intervention site women at 6 and 12 months. Unadjusted STI prevalence was 16.5 and 17.4% at 6 months, and 18.3 and 18.5% at 12 months, at the intervention and control sites, respectively. Logistic regression models confirmed the null effect of the female condom intervention. ConclusionsFemale condom introduction did not enhance STI prevention at these sites. It is unclear which aspects of the intervention – STI education, condom promotion, case management – were associated with decreased STI prevalence from baseline to follow-up.

Risk factors for copper T IUD expulsion: An epidemiologic analysis

Little is known of the factors associated with expulsion of intrauterine devices (IUD). We conducted a nested case-control study to examine the risk factors for copper T IUD expulsion using data from a multicenter international clinical trial. We included 70 cases with expulsion and 1,536 controls, and we examined a variety of characteristics of the IUD wearers. The proportional hazards model showed that young maternal age, abnormal amount of menstrual flow and dysmenorrhea before IUD insertion are risk factors for copper T IUD expulsion. The risk of expulsion steadily increased as age decreased, and as the severity of dysmenorrhea increased.

Moderate physical activity and bone density among perimenopausal women.

We examined the association between physical activity and bone mineral density (BMD) among 352 perimenopausal women. A personal activity computer was used to estimate the daily energy expenditure on physical activity. BMD was measured by photon absorptiometry at the lumbar spine, midradius, and distal radius. Multiple linear regression, controlling for other factors, indicated that physical activity was positively and significantly associated with BMD at all sites. Moderate physical activity has beneficial effects on BMD among perimenopausal women.

The use of nonoxynol-9 for protection against cervical gonorrhea.

OBJECTIVES Although condoms are the best defense against sexually transmitted disease, little is known about the effectiveness of female-controlled methods containing nonoxynol-9 as backup protection when condoms are not being used. METHODS To assess the extent to which nonoxynol-9 protects women against gonorrhea, a cohort of 303 female sex workers (prostitutes) in Yaounde, Cameroon, were asked to use condoms and suppositories containing nonoxynol-9 at every sexual encounter and to record daily sexual activity and use of condoms and suppositories on coital logs that were reviewed monthly. Evidence of gonorrheal infection was based on a positive gonorrhea culture. Stratified analysis and proportional hazards regression were used to estimate rate ratios. RESULTS Forty-one women enrolled in the study were excluded from the current analysis. The estimated incidence of gonorrhea was 6.2 infections per 100 person-months of observation. Incidence rate ratios estimated from proportional hazards regression models controlling for condom use showed that using nonoxynol-9 during acts not protected by condoms reduced the risk of infection. CONCLUSIONS Although the protective effect of condoms against sexually transmitted disease is greater than that afforded by nonoxynol-9, using nonoxynol-9 when condoms are not used is a far better strategy in gonorrhea prevention than using no method at all.

Contraceptive use and HIV infection in Kenyan family planning clinic attenders

This pilot study aimed to determine the feasibility of a larger study of contraception and risk of HIV infection in women. We also measured risk factors for and occurrence of HIV infection in the participants. A cohort of 1537 seronegative women attending a family planning clinic in Nairobi, Kenya was enrolled and followed for up to 12 months per woman. HIV testing was done quarterly. A nested case-control analysis was done with seroconverting women (cases) and 3 matched controls per case, who had detailed interviews and received physical examinations and STD tests. The prevalence of HIV at enrolment was 6.1%; seropositive women were excluded from further analysis. The 12-month life-table cumulative incidence of HIV was 2.1 per 100 women (95% confidence interval [CI] 1.1-3.2). In the nested case-control analysis (17 cases and 51 controls), the crude odds ratio of HIV infection comparing oral contraceptive (OC) users with other women was 3.5 (95% CI 0.8- 21.5), which persisted after control for single confounders at a time. The putative association between OC use and HIV infection is critical to public health policy, yet no study has been conducted specifically to measure it, yielding weak and conflicting evidence. We intend to conduct a larger study with a similar design as the current pilot study, which confirmed the feasibility or a more definitive project.

A comparison of different laparoscopic sterilization occlusion techniques in 24,439 procedures

This investigation assessed the safety and efficacy of five laparoscopic tubal occlusion techniques for female sterilization: electrocoagulation, the tubal ring via conventional and open laparoscopy, the prototype spring-loaded clip, and the Rocket clip. The 24,439 cases make up a data set collected by collaborating staffs at 64 institutions in 27 countries. The five techniques were compared with respect to six commonly evaluated parameters. Rates of surgical difficulties ranged from 2.4% to 12.5% (5.1% overall); rates of surgical complications, from 0.7% to 2.7% (1.7% overall); and rates of technical failures, from 0.6% to 1.0% (0.8% overall). Twelve-month life-table pregnancy rates were less than one per 100 women years. Prospective data on six menstrual parameters revealed that the menstrual cycles of the majority of women were unchanged after sterilization; for those who reported a change, approximately half experienced a change in one direction and half in the other direction. For example, one half reported an increase in the amount of menstrual flow, and one half reported a decrease in the amount of flow. The reported incidence of subsequent pelvic operations was less than 1% at each long-term follow-up. These data indicate that laparoscopic sterilization is safe and effective and that none of the studied techniques has a distinct advantage.

Gonorrhea as a risk factor for HIV acquisition.

ObjectiveThe role of gonorrhea in facilitating acquisition of HIV infection has only recently been studied. A previous nested case-control analysis in a cohort of female sex workers in Zaïre found a strong association between HIV seroconversion and prior gonorrheal infection. The objective of this study was to replicate the Zaïre study analysis in a cohort of 273 Cameroonian sex workers to determine whether gonorrhea increased the risk of HIV acquisition, and if the crude association between gonorrheal infection and HIV acquisition was weakened when the level of unprotected coitus was more carefully controlled. MethodsWe conducted a nested case-control study of initially HIV-1-negative women (n = 273) followed prospectively (with monthly sexually transmitted disease check-ups and 3-monthly HIV-1 serology). As in Zaire, cases (seroconverters, n = 17) were compared with controls (women who remained HIV-1-negative, n = 68) for incidence of gonorrhea and sexual exposure during the presumed period of HIV-1 acquisition. ResultsThe association between gonorrheal infection and subsequent HIV acquisition was stronger in Zaire than in Cameroon [crude odds ratios (OR), 6.3 versus 2.2]. In both the Zaïre and Cameroon data the crude OR were reduced (6.3 to 4.8, and 2.2 to 1.7, respectively) by controlling for risk factors including a dichotomous variable indicating irregular or no condom use. When this variable was replaced in the Cameroon data with a more precise continuous variable indicating the percentage of unprotected coital acts, the gonorrhea OR was further reduced to 1.4 (95% confidence interval, 0.4–4.9). ConclusionThese results suggest that in the Cameroon cohort, gonorrheal infection did not facilitate HIV acquisition, but that having gonorrhea was a marker for unprotected coitus that facilitated HIV acquisition. The data demonstrate how OR can be overestimated when imprecise dichotomous measures of unprotected coitus are used. Future studies should plan for better control of self-reported condom use.