Levels of HIV-1 RNA in endocervical specimens fluctuate with the menstrual cycle, suggesting that cell-free HIV-1 levels may vary during the cycle, which could influence infectivity. Here, we examined daily changes in endocervical HIV-1-infected cells during 1 cycle. There were significant positive associations between the number of days from the luteinizing hormone surge and the number of HIV-1 DNA copies/swab (P = 0.001) and the number of total cells/swab (P < 0.001) in endocervical specimens. These data suggest that sampling of cell-associated endocervical HIV-1 increases after the periovulatory period, which could result in increased exposure to HIV-1-infected cells during sexual contact.

Observational studies have suggested that low serum β-carotene concentrations may influence HIV-1 disease progression. However, randomized trials have not demonstrated beneficial effects of β-carotene supplementation. To understand this discrepancy, we conducted a cross-sectional study among 400 HIV-1-seropositive women in Mombasa, Kenya, to correlate serum β-carotene concentrations with several measures of HIV-1 disease severity. β-Carotene concentrations were significantly associated with biologic markers of HIV-1 disease progression (CD4 count, HIV-1 plasma viral load, serum C-reactive protein [CRP] concentration, and serum albumin level). In multivariate analysis, β-carotene concentrations below the median were associated with elevated CRP (>10mg/l, adjusted odds ratio [aOR] 3.32, 95% confidence interval [CI] 1.99–5.53, P <0.001) and higher HIV-1 plasma viral load (for each log10 copies/mL increase, aOR 1.38, 95% CI 1.01–1.88, P = 0.04). In the context of negative findings from randomized trials of β-carotene supplementation in HIV-1-seropositive individuals, these results suggest that low β-carotene concentrations primarily reflect more active HIV-1 infection rather than a deficiency amenable to intervention.

Background Early studies of the dynamics of HIV-1 transmission in Africa identified biological co-factors that influenced the risk of HIV-1 acquisition. Examples of this include STI, genital ulcers, and male circumcision1–3. To varying degrees, these are each host factors that can potentially be modified to reduce the risk of HIV-1 acquisition. An epidemiological study conducted among female prostitutes in Nairobi, Kenya, and published in 1991 found that oral contraceptive use was associated with an increased risk of HIV-1 infection2. Other prospective studies published between 1993 and 1996 found no association or even a decreased risk of HIV-1 infection in association with hormonal contraceptives3–5. Three studies published between 1992 and 1996 found positive associations between intramuscular depomedroxyprogesterone acetate (DMPA) and HIV-1 seropositivity or HIV-1 acquisition6–8. Therefore, at that time, there was no consensus regarding the effect of hormonal contraception and a woman's risk of acquiring HIV-1 infection. Because of the potential importance of any such association, it was recognized that there was a need to evaluate whether hormonal contraceptives were another modifiable factor that might influence HIV-1 transmission. Hormonal contraceptives continue to be the most popular choice of fertility control for sexually active women, and any effect that they may have on HIV-1 acquisition could have a significant effect on the dynamics of the HIV epidemic. In 1993, a prospective cohort study began in female prostitutes in Mombasa, Kenya, to examine the relationship between hormonal contraception, STI, and HIV-1 acquisition9. A unique aspect of this study was the frequent follow-up schedule for women, which allowed an accurate estimation of the timing of HIV-1 acquisition and a precise measurement of hormonal contraceptive use, thereby reducing the chance of the misclassification of contraceptive exposure. Studies Prospective Cohort Study We initiated a prospective cohort study in February 1993 among HIV-1-seronegative female prostitutes attending a municipal STI clinic in Mombasa, Kenya. The study was specifically designed to investigate the correlates of HIV-1 acquisition. For this reason, women were seen on a monthly basis, and contraceptive information was collected at each visit. Monthly interviews and physical examinations focused on sexual behavior, contraceptive use, and STI diagnosis and treatment. HIV serology was performed at each visit to allow a more accurate estimation of the time of HIV-1 infection. In the analysis of the relationship between hormonal contraceptive use and HIV-1 acquisition, hormonal contraceptive use was treated as a time-dependent variable. This variable was ‘on’ if a woman had used hormonal contraceptives within 115 days of a study visit. This stringent method for determining exposure to hormonal contraceptives was used to reduce the misclassification of contraceptive use and to establish a strict temporal linking of contraceptive use and HIV-1 infection. A total of 779 women who were enrolled and returned for follow-up were included in the final analysis. The median follow-up time was 224 days, and 880 PY of follow-up were accumulated. One hundred and eleven women seroconverted to HIV-1, and the median number of days between the last negative and first positive HIV test for these women was 57 days. At baseline, oral contraceptives were used by 16% of women, and 15% used DMPA. The one-year HIV-1 incidence rate was 15% (95% CI 11–18%). In univariate analysis, women using DMPA had an HR of HIV-1 infection of 2.2 (CI 1.4–3.4) compared with women using no hormonal contraception. A trend for increased risk of HIV-1 infection was seen among OC users compared with women using no hormonal contraception (HR 1.5; CI 0.9–2.4). When oral contraceptives were divided into high-dose and low-dose pills on the basis of contraceptive steroid content, high-dose pill users had an adjusted HR for HIV-1 infection of 2.3 (CI 0.7–7.5), whereas low-dose pill users had an HR of 1.5 (CI 0.8–2.7). Multivariate analysis was conducted to control for possible confounding by demographic, sexual exposure, or biological variables. Condom use was included in multivariate models to control for its protective effect on HIV-1 acquisition. In the final model, DMPA use remained significantly associated with HIV-1 infection (HR 2.0, CI 1.3–3.1), and a trend was present for high-dose oral contraceptive use (HR 2.6, CI 0.8–8.5, P = 0.1). Findings for univariate and multivariate models are presented in Table 1.TABLE 1: Association Between Method of Contraception and HIV-1 Acquisition9Meta-analysis As a result of the ongoing controversy surrounding hormonal contraceptive use and HIV-1 infection, Wang et al.10 conducted a meta-analysis of 28 published studies that examined the association between OC use and HIV-1. Heterosexual transmission was the primary mode of HIV-1 infection in all studies included in the meta-analysis. Study populations included sex workers, STI clinic attendees, discordant couples, and family planning, antenatal, HIV, and primary care clinic attendees. Sixty-eight per cent of studies reported an odds ratio (OR) of greater than one, and an overall summary OR of 1.19 (CI 0.99–1.42) was calculated. When examined by study design, cross-sectional studies had a summary OR of 1.21 (CI 1.01–1.44) and prospective studies had an OR of 1.32 (CI 1.12–1.57). When studies were graded on the quality of measurement of contraceptive use, the highest scoring studies had a calculated OR of 1.60 (CI 1.05–2.44). When limited to studies conducted in Africa, the OR was 1.45 (CI 1.15–1.83), and the highest quality African studies had a calculated OR of 1.65 (CI 1.09–2.52). The findings from this meta-analysis are summarized in Table 2.TABLE 2: Summary Odds Ratios for Association Between HIV-1 Serostatus and Use of Oral Contraceptives10Conclusion The results of a large, open, prospective cohort study in female prostitutes in Mombasa, Kenya, found a significant association between DMPA use and HIV-1 infection. A trend was found between the use of high-dose OCs and the acquisition of HIV-19. These associations are supported by a meta-analysis of 28 studies that found a positive association between OC use and HIV-1 acquisition.10 In addition, studies in the SIV macaque model have also demonstrated that there is an effect of progesterone on vaginal SIV acquisition11. It is interesting that in the Mombasa sex worker cohort we have observed a propensity for women to be infected by multiple diverse variants of HIV-112,13. The transmission of multiple viruses suggests increased susceptibility of the host to HIV-1 infection. It is thus noteworthy that approximately 60% of women in this cohort were infected by multiple variants, whereas none of the 10 men from Mombasa who were examined in parallel were infected by multiple viruses during heterosexual exposure13. Studies are underway to determine whether the use of hormonal contraceptives is linked to infection by a genetically heterogeneous virus population. It is now more than 10 years since subject no. 1001 (the first subject) was enrolled in the Mombasa cohort. The first presentation of data from the Mombasa cohort at the Tenth International Conference on AIDS, in Yokohama, Japan, in 1994 was met with scepticism. Discussions at this conference demonstrated that uncertainty remains. Several other studies have found no association between hormonal contraceptives and HIV-1 risk. Rather than dismissing either conclusion as false, we should examine why diverse results have been reported. One important factor could be that the measurement of contraceptive exposure and the temporal linking of contraception and HIV infection vary across the different studies. A less accurate and less frequent measurement of exposure to contraceptives would probably result in increased misclassification bias and a tendency towards the null hypothesis of no effect. Another potential factor for variable results from different studies on hormonal contraceptive use and HIV-1 acquisition is that this variation may simply reflect real differences between risk populations. Studies of high-risk populations, such as the Mombasa sex workers, who have multiple sex partners and may be exposed to multiple HIV-1 viral variants, indicate that such groups are at increased risk of infection if they use hormonal contraceptives. However, it is possible that, for other risk groups such as monogamous women, hormonal contraceptive use does not significantly alter the risk of HIV-1 acquisition. Further studies of these different populations using frequent monitoring and accurate measures of contraceptive exposure may help to clarify any differences between risk groups and the differences seen in the results from different studies. In the interim, any fertility regulation counseling must be coupled with education about HIV and STI and condom promotion for disease prevention.

BACKGROUND:A lack of male circumcision has been associated with increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition in a number of studies, but questions remain as to whether confounding by behavioral practices explains these results. The objective of the present study was to model per-sex act probabilities of female-to-male HIV-1 transmission (i.e., infectivity) for circumcised and uncircumcised men, by use of detailed accounts of sexual behavior in a population with multiple partnerships.METHODS:Data were collected as part of a prospective cohort study of HIV-1 acquisition among 745 Kenyan truck drivers. Sexual behavior with wives, casual partners, and prostitutes was recorded at quarterly follow-up visits. Published HIV-1 seroprevalence estimates among Kenyan women were used to model HIV-1 per-sex act transmission probabilities.RESULTS:The overall probability of HIV-1 acquisition per sex act was 0.0063 (95% confidence interval, 0.0035-0.0091). Female-to-male infectivity was significantly higher for uncircumcised men than for circumcised men (0.0128 vs. 0.0051; P=.04). The effect of circumcision was robust in subgroup analyses and across a wide range of HIV-1 prevalence estimates for sex partners.CONCLUSIONS:After accounting for sexual behavior, we found that uncircumcised men were at a >2-fold increased risk of acquiring HIV-1 per sex act, compared with circumcised men. Moreover, female-to-male infectivity of HIV-1 in the context of multiple partnerships may be considerably higher than that estimated from studies of HIV-1-serodiscordant couples. These results may explain the rapid spread of the HIV-1 epidemic in settings, found throughout much of Africa, in which multiple partnerships and a lack of male circumcision are common.

portant in light of a recent study showing that 14% of prostitutes in a Kenyan sample admitted to having anal intercourse [5].Were data on anal exposures sought?Considering the substantial reported anomalies in the "heterosexual transmission" view of HIV dynamics in sub-Saharan Africa [6] and reports of data-based estimates that much transmission may be due to undersuspected and underevaluated parenteral exposures [7,8], care must be taken to ask precise questions and to control for confounding variables, especially in poor countries where parenteral exposure may play a larger role in HIV-1 transmission than heretofore believed.Failure to address such potential threats to validity undermines the credibility of the "female-to-male" or "penile-vaginal" HIV-1 transmission efficiency estimates for circumcised and uncircumcised men that the authors present.Finally, mathematical models using potentially invalid estimates should be evaluated with appropriate circumspection.

There are multiple subtypes of HIV-1 circulating worldwide, but recently, subtype C has become highly prevalent, particularly in certain geographic regions. It is unclear whether the dominance of subtype C or other subtypes is due to increased fitness of certain subtypes for transmission, or a founder effect in new, rapidly growing epidemics. To examine whether the prevalence of one subtype increases over the course of an expanding epidemic that includes several circulating subtypes, we examined the distribution of HIV-1 subtypes in Kenya from 1986 to 2000. We found no evidence for an increase in the prevalence of subtype C, which remained low throughout this approximately 15-year period. Interestingly, the percentage of subtype D present in the population decreased significantly over that period, with a slight increase in subtype A. Throughout that period, intersubtype recombinant viruses were detected, including at the early stages of the epidemic. This latter finding suggests that reinfection may have occurred in high-risk groups early in the epidemic, leading to intersubtype recombinant viruses that underwent secondary spread.

Objective To assess the effect of steroid hormone contraceptive methods on the clinical course of early HIV infection among women in Kenya, Thailand and Zimbabwe. Methods Women with documented HIV infection and CD4 cell counts over 500 cells/μl who were asymptomatic or had early (mild disease) were invited to participate in an observational cohort study with 6-monthly follow-up visits for 4 years. Baseline information was collected through interview, physical examination and blood sample collection for CD4 cell count, HIV quantification and subtyping. Identical procedures were repeated at each follow-up visit. Study endpoints include HIV disease progression, the incidence of opportunistic infections (OI), and surrogate markers of disease progression, including changes in CD4 cell counts and viral load. These will be analysed according to the contraceptive methods used. The study aimed to recruit a total of 220 users each of DMPA, Norplant, COC and a similar number of women not using hormonal contraception over the study sites. Results Recruitment to the study started in 2000 and by the middle of 2002 a total of 395 women had been recruited, the majority of whom were from Nairobi (52%) and Harare (23%). One quarter of women were using COC, 42% DMPA, 5% Norplant and the remaining 28% non-hormonal contraception at enrolment. Almost all the Norplant users were from Bangkok and almost all the COC and DMPA users were from the two African sites. Few HIV endpoints have occurred in the cohort to date. CD4 cell counts at enrolment were lower in Harare than in Nairobi, despite the selection of women with counts above 500 cells/μl. Preliminary assessment of the rates of CD4 cell decline showed a higher rate in Harare (mean annual loss of 102 cells/μl; SD 244) than in Nairobi (mean annual loss of 55 cells/μl; SD 283). Recruitment into the cohort continued through 2003 and follow-up will continue for the enrolled women up to the scheduled four completed years. The study is estimated to have 80% power to demonstrate twofold differences in the rates of CD4 cell decline between oral contraceptive and non-hormonal users, as well as between DMPA and non-hormonal users. Conclusion Recruitment into the study has been difficult, particularly as the study was not able to offer any promise of therapy for HIV-positive women. Plans to provide antiretroviral therapy to those women whose CD4 cell counts decline below 200 cells/μl are under development and will allow the clinical response to antiretroviral therapy to be assessed in the well-documented cohort of steroid hormone contraception users. Recruitment to the study had to be abandoned in Brazil as the national standards for therapy meant that there would at best be only a short period of observation before the volunteers qualified for treatment, and it proved very difficult to identify HIV-positive women with CD4 cell counts over the study threshold for enrolment. Support Financial support for the study was provided by the World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Geneva, Switzerland.

Objective: To evaluate the relationship between hormonal contraceptive use and the acquisition of cervical sexually transmitted infections (STI) among HIV-1-infected women. Design: A prospective cohort study of 242 commercial sex workers in Mombasa, Kenya, followed from the time of HIV-1 infection. Methods: At monthly follow-up visits, sexual behavior and contraceptive use were recorded, and laboratory screening for STI was performed. Multivariate Andersen–Gill proportional hazards models were constructed to examine the association between the use of hormonal contraception and the occurrence of cervical STI. Results: The median duration of follow-up after HIV-1 acquisition was 35 months, and 799 person-years of follow-up were accrued. After adjustment for demographic factors and sexual behavior, women using the injectable contraceptive depot medroxyprogesterone acetate were at increased risk of Chlamydia trachomatis infection [hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0–9.4, P = 0.05] and cervicitis (HR 1.6, 95% CI 1.0–2.3, P = 0.03) compared with women using no contraception. The use of oral contraceptive pills was associated with an increased risk of cervicitis (HR 2.3, 95% CI 1.4–3.8, P = 0.001). Hormonal contraception was not associated with an increased risk of infection with Neisseria gonorrhoeae. Conclusion: The use of hormonal contraception by HIV-1-infected women was associated with an increased risk of cervicitis and cervical chlamydia infection. HIV-1-seropositive women using hormonal contraception should be counseled about the importance of consistent condom use to prevent both STI and HIV-1 transmission.

Background: Most studies that have found an association between uncircumcised status and infection with human immunodeficiency virus type 1 (HIV-1) have compared participants from various demographic backgrounds, among which the prevalence of other risk factors might have varied. We report findings from a study conducted among men within a single ethnic community in which circumcision was dictated by the religious denomination to which the men belonged. Methods: Of the 1217 eligible men, we included in the analysis 845 who gave blood samples for HIV-1 testing and who were confirmed as either fully circumcised (n = 398) or uncircumcised (n = 447). The seroprevalence of HIV-1 was compared between the 2 groups. Results: All correlates of HIV-1 prevalence that we measured were distributed similarly between circumcised and uncircumcised men. The seroprevalence of HIV-1 was 30% among the uncircumcised men and 20% among the circumcised men. Among uncircumcised men, HIV-1 seroprevalence was similar between men from circumcising denominations (31%; n = 111) and noncircumcising denominations (30%; n = 336). The crude prevalence ratio for HIV infection associated with not being circumcised was 1.5 (95% confidence interval = 1.2–2.0); and adjustment for other measured risk factors for HIV-1 infection had little impact on this result. Conclusion: Our study provides evidence that circumcision is associated with a reduced risk of HIV-1 infection.

To test the hypothesis that micronutrient supplementation decreases genital HIV-1 shedding, a double-blind, randomized, placebo-controlled trial of 6 weeks of multivitamin plus selenium supplementation vs. placebo was conducted among 400 HIV-1-seropositive, nonpregnant, antiretroviral-naive women in Mombasa, Kenya. Primary outcome measures included cervical and vaginal shedding of HIV-1-infected cells and RNA. Secondary outcomes included plasma viral load and CD4 count. Surprisingly, the odds of detection of vaginal HIV-1-infected cells were 2.5-fold higher (P = 0.001) and the quantity of HIV-1 RNA in vaginal secretions was 0.37 log10 copies/swab higher (P = 0.004) among women who received micronutrients in comparison to placebo, even after adjustment for potential confounders including baseline HIV-1 shedding and CD4 count. The increase in vaginal HIV-1 shedding was greatest among women who had normal baseline selenium levels. Micronutrient supplementation resulted in higher CD4 (+23 cells/microL, P = 0.03) and CD8 (+74 cells/microL, P = 0.005) counts compared with placebo but did not alter the plasma viral load. In this randomized trial, micronutrients resulted in higher levels of genital HIV-1 shedding compared with placebo. The potential benefit of micronutrient supplementation in HIV-1-seropositive women should be considered in relation to the potential for increased infectivity.

The association between hormone fluctuations during the menstrual cycle and human immunodeficiency virus type 1 (HIV-1) RNA shedding in cervical and vaginal secretions was examined daily for 17 HIV-1-seropositive women, for the duration of 1 cycle. Serum levels of RNA were evaluated 3 times/week. A marginally significant positive correlation between serum levels of progesterone and serum levels of HIV-1 RNA (P=.04) was observed. Cervical virus levels were significantly correlated with the number of days from the midcycle surge in luteinizing hormone (LH) (P=.008). The lowest levels of cervical HIV-1 RNA were present at the LH surge, and this nadir was followed by an increase in virus levels that reached a maximum before the start of menses. In contrast, there was no significant association between the number of days from the LH surge and the level of HIV-1 RNA in vaginal secretions (P=.4). These data support the hypothesis that the level of HIV-1 RNA in cervical secretions is influenced by the menstrual cycle, and they suggest that the risk of heterosexual transmission of HIV-1 may increase as menses is approached.

Polymerase chain reaction was used to determine the prevalence and correlates of human herpesvirus 8 (HHV8) in saliva, mouth, cervical, vaginal, plasma, and peripheral-blood mononuclear cell (PBMC) samples from 174 HHV8-seropositive female prostitutes in Mombasa, Kenya. The prevalence of detection of HHV8 was 32% in saliva samples, 28% in mouth swabs, 4% in cervical swabs, 2.3% in vaginal swabs, 9% in plasma samples, and 18% in PBMC samples. Human immunodeficiency virus type 1 (HIV-1) seropositivity was associated with detection of HHV8 from any mucosal surface (odds ratio, 2.1 [95% confidence interval, 1.1-4.0]). In HIV-1-seropositive women, there was no association between detection of HHV8 and either CD4 count or HIV-1 viral load.

Understanding how the level of human immunodeficiency virus type 1 (HIV-1)-infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1-infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R = .144; P = .032), levels of cell-free virus in blood plasma (R = .365; P < .001), and the detection of proviral DNA in cervical and vaginal secretions (P < .001 and P = .030, respectively). The number of infected BMCs per million cells was lower in colostrum or early milk than in mature milk (P < .001). Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P < .001). Each log(10) increase in infected BMCs per milliliter was associated with a 3.19-fold-increased risk of transmission (P = .002), after adjustment for cell-free virus in plasma (hazard ratio [HR], 2.09; P = .03) and breast milk (HR, 1.01; P = 1.00). This suggests that infected BMCs may play a more important role in transmission of HIV via breast- feeding than does cell- free virus.

Cross-sectional analyses have associated vitamin A deficiency with genital shedding of herpes simplex virus (HSV) among human immunodeficiency virus type 1 (HIV-1)-infected women. A randomized clinical trial of vitamin A supplementation given daily for 6 weeks was conducted among 376 women in Mombasa, Kenya, who were coinfected with HSV-2 and HIV-1. At follow-up, there was no significant difference in the detection of genital HSV DNA between women receiving vitamin A supplementation and women receiving placebo (40% vs. 44%, respectively; P = .5) Among women shedding HSV, there was no significant difference in the mean HSV DNA quantity between the group that received vitamin A supplementation and the group that received placebo (4.51 vs. 4.67 log10 copies/swab; P = .6). HSV shedding was associated with significantly higher vaginal and cervical HIV-1 shedding, even after controlling for the plasma HIV-1 load and the CD4 count. Vitamin A supplementation is unlikely to decrease HSV shedding and infectivity.

Background: Human herpesvirus 8 (HHV-8) antibody tests vary in reported sensitivity and specificity, depending on the population tested and the assay. Objective: The purpose of this study was to compare the ability to detect seroconversion to HHV-8 in a cohort of HHV-8 seronegative female commercial sex workers in Kenya using three tests: HHV-8 viral lysate-based enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay for HHV-8 lytic antigens (IFA-lytic) and IFA for latent nuclear antigens (IFA-LANA). Study design: By ELISA, 16 women from a prospective cohort of commercial sex workers were identified as seroconverting to HHV-8. A total of 124 post-enrollment samples from these 16 women as well as the enrollment samples were tested for HHV-8 antibodies by all three assays to monitor seroconversion. Results: Of 16 women with apparent seroconversion by ELISA, 8 had a rise in IFA-lytic titers either concomitant with or prior to the first positive ELISA sample and no initial LANA by IFA. Five of the 16 women were IFA-LANA positive at entry, indicating prior infection with HHV-8. Three women had no evidence of seroconversion by either IFA-lytic or IFA-LANA and two of these three had increased ELISA reactivity concomitant with HIV-1 infection. Conclusions: Conversion from a negative to a positive ELISA result for HHV-8 antibody indicated seroconversion in only half of the study cohort of 16 women when IFA-lytic and IFA-LANA results were considered. The IFA-lytic assay was more sensitive than ELISA for early antibody responses. The IFA-LANA was positive in some women who had neither IFA-lytic nor ELISA antibodies suggesting it may be a marker for latent infections. Presumptive identification of incident HHV-8 infection by ELISA screening followed by IFA-lytic testing to confirm the positive test and IFA-LANA to rule out prior infection provides the most accurate documentation of HHV-8 seroconversion.

The use of hormonal contraception has been associated with an increased risk of HIV-1 in some studies but not in others. We analysed data from a 10-year prospective cohort study of female sex workers in Mombasa, Kenya. In multivariate analysis, women using the injectable contraceptive depot medroxyprogesterone acetate and women using oral contraceptive pills were at increased risk of HIV-1 acquisition compared with women using no contraceptive method.

BACKGROUND:Serum retinol is the most commonly used indicator of vitamin A status. Retinol is transported in a 1-to-1 complex with retinol-binding protein (RBP). RBP is easy and inexpensive to measure, and studies have shown a high correlation between concentrations of RBP and concentrations of retinol. The performance of RBP in the context of infection or protein malnutrition, however, has not been evaluated.OBJECTIVE:Our aim was to determine whether RBP is a good surrogate measure for retinol in the context of HIV-1 infection, protein malnutrition, and the acute phase response.DESIGN:The relation between RBP and retinol was examined in a cross-sectional study of 600 Kenyan women.RESULTS:There was a high correlation between concentrations of RBP and those of retinol (r = 0.88). When equimolar cutoffs were used, RBP predicted marginal vitamin A status (retinol < 1.05 micro mol/L) with 93% sensitivity and 75% specificity and vitamin A deficiency (retinol < 0.70 micro mol/L) with 91% sensitivity and 94% specificity. Similarly high sensitivities and specificities were found among subgroups with HIV-1 infection, a positive acute phase response, and protein malnutrition. Protein malnutrition and a positive acute phase response were common, especially among HIV-1-infected women, and were independently and synergistically associated with lower RBP concentrations.CONCLUSIONS:Equimolar RBP cutoffs predict vitamin A deficiency with high sensitivity and specificity, even in the context of infection and protein malnutrition. Like retinol, RBP may not accurately identify true vitamin A status under all conditions, because the acute phase response and protein malnutrition depress RBP concentrations. However, RBP may be a simple, inexpensive tool for assessment of vitamin A deficiency in population studies.

Background: Our previous studies have shown that the majority of African women were infected with multiple HIV-1 genetic variants, while in the remaining women only a single viral genotype was detected early in infection. Infection with multiple viral variants was associated with higher plasma HIV-1 RNA levels and faster CD4 T-cell decline. Method: Socio-behavioral characteristics, use of hormonal contraceptives, and the presence of sexually transmitted diseases were prospectively assessed at approximately monthly intervals around the time of HIV-1 acquisition in female sex workers in Kenya. We assessed the relationship between these factors and HIV-1 genetic complexity early in infection. Results: One hundred and fifty-six women were included in this analysis, of whom 89 had multiple viral genotypes and 67 had a single genotype at primary infection. Women with multiple variants were more likely to have a genital tract infection [odds ratio (OR), 4.7; 95% confidence interval (CI), 1.4–18.1] or to be using hormonal contraceptives (OR, 2.7; 95% CI, 1.3–5.6) at the time of their infection than those with a single variant. In multivariate analyses, these factors were independent predictors of early HIV-1 genetic complexity, and the presence of multiple viral variants early in infection remained significantly associated with a higher steady state plasma HIV-1 RNA level. Conclusion: The presence of genital tract infections and hormonal contraceptive use at the time of transmission were associated with the acquisition of multiple HIV-1 variants.