Heterosexual Human Immunodeficiency Virus Research Articles

2-Hydroxyisovalerate Is Produced During Bacterial Vaginosis and Boosts HIV Infection in Resting T Cells.

Human immunodeficiency virus (HIV) infection and the ensuing acquired immunodeficiency syndrome (AIDS) disproportionally affect young women, yet understanding of the factors promoting heterosexual transmission in the female genital tract is limited. Colonization with highly diverse, Lactobacillus-deficient communities (HDCs) increases a woman's risk of acquiring HIV-1 compared with colonization with Lactobacillus-dominated low diversity communities (LDCs). The polymicrobial nature of these communities has made it challenging to elucidate the microbial mechanisms responsible for modulating HIV susceptibility. Here, we analyzed conserved changes in small-molecule metabolites present in the cervicovaginal lavage fluid collected from women colonized with HDCs and LDCs with the goal of identifying possible chemicals influencing HIV infection. As in previous studies, we found that the catabolite of the branched-chain amino acid valine, 2-hydroxyisovalerate (2-HV), was a consistent component of dysbiotic HDC microbiota. Effects of 2-HV on HIV infection were assessed. In experimental infections with HIV, treatment with 2-HV increased infections of resting CD4+ T cells. To understand bacterial production of 2-HV in more detail, we cultured purified HDC and LDC bacteria and used mass spectrometry to identify two HDC bacteria that synthesize high levels of 2-HV. In contrast, protective vaginal Lactobacilli did not produce high levels of 2-HV. A genomic analysis of genes encoding 2-HV synthetic pathways showed a correlation between high-level production of 2-HV and pathways for synthesis of the immediate precursor 2-ketoisovalerate. Thus, 2-HV is a candidate mediator linking vaginal microbiome structure and heterosexual HIV transmission in women.

Factors Associated with Low Uptake of Medical Male Circumcision Among Adolescent Boys in Tanzania: A Multinomial Logistic Regression Modeling.

Human immunodeficiency virus (HIV) remains the leading cause of years of life lost among adolescent boys in eastern and southern Africa. Medical male circumcision (MMC) is a cost-effective one-time intervention that can reduce the risk of heterosexual HIV acquisition in men by approximately 60%. Despite its importance in HIV prevention, the uptake of MMC remains suboptimal among adolescent boys. This study aimed to identify factors associated with low MMC uptake among adolescent boys in Tanzania. This study was a secondary analysis of the 2016-17 Tanzania HIV Impact Survey. Descriptive statistics were used to summarize the participants' characteristics. Unadjusted and adjusted multinomial logistic regression models were fitted to identify factors associated with low MMC uptake among adolescent boys. A total of 2605 older adolescents (15-19 years) and 1296 young adolescents (10-14 years) were analyzed. The MMC uptake rates among older and young adolescents were 56.5% and 45.1%, respectively. Lower MMC uptake was found among respondents in rural areas (adjusted relative risk ratio [aRRR] = 0.40, 95% CI: 0.28-0.57), in the traditionally non-circumcising zone (aRRR = 0.30, 95% CI: 0.23-0.41), participants with no formal education (aRRR = 0.32, 95% CI: 0.23-0.41), and those living in lower wealth quintile households (aRRR = 0.20, 95% CI: 0.11-0.36). Respondents who were not covered by health insurance (aRRR = 0.67, 95% CI: 0.48-0.94) and those who had no comprehensive HIV knowledge (aRRR = 0.55, 95% CI: 0.44-0.70) were also found to have lower uptake of MMC. To achieve and maintain high MMC coverage, MMC interventions for HIV prevention should focus on uncircumcised adolescent boys who are rural residents, of lower socioeconomic status, and residing in traditionally non-circumcising communities. Furthermore, dissemination of HIV knowledge and increasing health insurance coverage may encourage more adolescent boys to undergo MMC.

Cost-effectiveness analysis of 'test and treat' policy for antiretroviral therapy among heterosexual HIV population in India.

The World Health Organisation recommended immediate initiation of antiretroviral therapy (ART) in all adult human immunodeficiency virus (HIV) patients regardless of their CD4 cell count. This study was undertaken to ascertain the cost-effectiveness of implementation of these guidelines in India. A Markov model was developed to assess the lifetime costs and health outcomes of three scenarios for initiation of ART treatment at varying CD4 cell count <350/mm[3], <500/mm[3] and test and treat using health system perspective using life-time horizon. A few input parameters for this model namely, transition probabilities from one stage to another stage of HIV and incidence rates of TB were calculated from the data of Centre of Excellence for HIV treatment and care, Chandigarh; whereas, other parameters were obtained from the published literature. Total HIV-related deaths averted, HIV infections averted and incremental cost-effectiveness ratio per quality adjusted life years (QALYs) gained were calculated. Test and treat intervention slowed down the progression of disease and averted 18,386 HIV-related deaths, over lifetime horizon. It also averted 16,105 new HIV infections and saved 343,172 QALYs as compared to the strategy of starting ART at CD4 cell count of 500/mm[3]. Incremental cost per QALY gained for the immediate initiation of ART as compared to ART at CD4 cell count of 500/mm[3] and 350/mm[3] was ₹ 46,599 and 80,050, respectively at reported rates of adherence to the therapy. Immediate ART (test and treat) is highly cost-effective strategy over the past criteria of delayed therapy in India. Cost-effectiveness of this policy is largely because of reduction in the transmission of HIV.

Risk of Human Immunodeficiency Virus Acquisition Among High-Risk Heterosexuals With Nonviral Sexually Transmitted Infections: A Systematic Review and Meta-Analysis.

Nonviral sexually transmitted infections (STIs) increase risk of sexually acquired human immunodeficiency virus (HIV) infection. Updated risk estimates carefully scrutinizing temporality bias of studies are needed. We conducted a systematic review (PROSPERO CRD42018084299) of peer-reviewed studies evaluating variation in risk of HIV infection among high-risk heterosexuals diagnosed with any of: Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, Treponema pallidum, and/or Trichomonas vaginalis. We searched PubMed, Web of Science, and Embase databases through December 2017 and included studies where STIs and HIV were assessed using laboratory tests or medical examinations and where STI was diagnosed before HIV. After dual screening, data extraction, and risk of bias assessment, we meta-analytically pooled risk ratios (RRs). We found 32 eligible studies reporting k = 97 effect size estimates of HIV acquisition risk due to infection with one of the abovementioned STIs. Most data were based on women engaged in sex work or other high-risk occupations in developing countries. Many studies did not measure or adjust for known confounders, including drug injection and condom use, and most were at medium or high risk of bias because of the potential for undetected HIV infection to have occurred before STI infection. Human immunodeficiency virus acquisition risk increased among women infected with any pathogen; the effect was greatest for women infected with Mycoplasma genitalium (RR, 3.10; 95% confidence interval [CI], 1.63-5.92; k = 2) and gonorrhea (RR, 2.81; 95% CI, 2.25-3.50; k = 16) but also statistically significant for women infected with syphilis (RR, 1.67; 95% CI, 1.23-2.27; k = 17), trichomonas (RR, 1.54; 95% CI, 1.31-1.82; k = 17), and chlamydia (RR, 1.49; 95% CI, 1.08-2.04; k = 14). For men, data were space except for syphilis (RR, 1.77; 95% CI, 1.22-2.58; k = 5). Nonviral STI increases risk of heterosexual HIV acquisition, although uncertainty remains because of risk of bias in primary studies.

RISKY SEXUAL BEHAVIOR IN PEOPLE LIVING WITH HIV

Relevance. There is a continuing growth of infection with the human immunodeficiency virus (HIV) and the need for effective design of preventive measures.Intention. To explore features of risky sexual behavior in people living with HIV with and without substance abuse and in healthy respondents.Methodology. The study involved 136 individuals in the groups as follows: 1st (n = 50) – drug users with blood-borne HIV infection, 2nd (n = 50) – heterosexual HIV infection, 3rd (n = 36) – without HIV infection. A specially developed clinical map was used, as well as an original questionnaire recording the characteristics of risky behavior and the main characteristics of the life situation of the disease (“Infection risk and the disease situation”). Statistical data processing included the Fisher criterion (ϕ-criterion).Results and Discussion. The characteristics of respondents’ sexual behavior related to gender, the presence/absence of HIV and the transmission route were revealed in the study. It has been established that HIV-infected and healthy respondents do not differ in the frequency of barrier protection methods (condoms) use. Various variants of risky sexual behavior were noted in all groups, in particular, unjustified rejection of condoms. The results are partially confirmed in the published data. In the Russian sample, non-use of condoms and the prevalence of “trust in a partner” were studied for the first time.Conclusion. Important components of prevention programs include increasing sexual literacy and working with people who use psychostimulants and other drugs.

Parenting Desires Among Individuals Living With Human Immunodeficiency Virus in the United States.

BackgroundIn 1988, 1 of 3 women (W) and heterosexual men living with human immunodeficiency virus (HIV) reported wanting children, but little is known about parenting desires of men who have sex with men (MSM) living with HIV. We examined parenting desires among persons initiating antiretroviral therapy (ART).MethodsOf 1809 participants in the AIDS Clinical Trials Group (ACTG) Study 5257, 1425 W aged ≤45 years or men completed questionnaires about parenting desires at baseline and 96 weeks after initiating ART. Self-reported desires for children in the future (yes/unsure vs no) and associations between baseline sociodemographics and parenting desires at 96 weeks were examined using multivariable logistic regression, overall and within subgroups.ResultsThe 1425 participants were as follows: 36% white, 39% black, 22% Hispanic; median age 36 (interquartile range, 28–44); 70% MSM, 13% men reported sex only with W (MSW), 17% W. At baseline, 42% may want children in the future (42% MSM, 37% MSW, 43% W); at 96 weeks, 41% may want children (41% MSM, 37% MSW, 43% W). At follow-up, approximately 10% of responses changed in each direction. In multivariable analyses, education greater than high school, <30 years, and having no children were significantly associated with future parenting desires among all subgroups. Among MSM, being black was associated with desiring children.ConclusionsApproximately 40% of MSM, W, and MSW with HIV may want children, both at baseline and 96 weeks after ART initiation. These results highlight the need to regularly assess parenting goals, provide access to comprehensive reproductive services, and address prevention of vertical and heterosexual HIV transmission.

Antiretroviral Therapy Initiation Is Not Associated With Risky Sexual Behavior Among Heterosexual Human Immunodeficiency Virus-Infected Persons in Serodiscordant Partnerships.

Few prospective studies have assessed whether antiretroviral therapy (ART) use is associated with changes in sexual risk behavior of human immunodeficiency virus (HIV)-infected persons in known HIV-serodiscordant partnerships. We conducted a longitudinal analysis of HIV-infected persons with known uninfected partners enrolled in the Partners Pre-Exposure Prophylaxis Study in Kenya and Uganda. Antiretroviral therapy use and self-reported sexual behavior were ascertained every 3 months. We assessed the effect of ART on sexual risk behaviors using zero-inflated negative binomial regression. Primary outcomes were condomless vaginal sex acts, pregnancy incidence and new sexually transmitted infection diagnoses. We followed 1817 HIV-infected persons (58% women) for 864 person-years before ART initiation and 771 person-years after ART. Median CD4 and plasma viral load at ART initiation were 277 cells/μL and 4.18 log10 copies/mL. Antiretroviral therapy use was associated with a significant decrease in condomless vaginal sex acts with HIV-uninfected partners (0.65 vs 0.39 per month; rate ratio, 0.64; 95% confidence interval [CI], 0.55-0.75; P < 0.001), but not condomless vaginal sex acts with nonprimary partners (1.30 vs 1.04 per month; rate ratio, 0.94; 95% CI, 0.94-1.20; P = 0.62). Pregnancy incidence was lower after ART (13.2 vs 8.4 per 100 person-years; HR, 0.71; 95% CI, 0.60-0.84; P < 0.001). Incident sexually transmitted infection diagnoses were similar (odds ratio, 1.05; 95% CI, 0.86-1.29; P = 0.63). Substantial risk compensation did not occur after ART initiation among East African HIV-infected persons with known HIV-uninfected partners. These data inform modelling studies of ART for HIV prevention by suggesting that risky sexual behavior did not appear to offset decreased HIV infectiousness in this key population.

Can the Heterosexual HIV Epidemic be Eliminated in South Africa Using Combination Prevention? A Modeling Analysis.

Little is known about how combining efficacious interventions for human immunodeficiency virus (HIV) prevention could lead to HIV elimination. We used an agent-based simulation model, the HIV calibrated dynamic model, to assess the potential for HIV elimination in South Africa. We examined several scenarios (from continuation of the current status quo to perfect achievement of targets) with differing combinations of male condom use, adult male circumcision, HIV testing, and early antiretroviral therapy (ART). We varied numerous parameters, including the proportion of adult males circumcised, the frequency of condom use during sex acts, acceptance of HIV testing, linkage to health care, criteria for ART initiation, ART viral suppression rates, and loss to follow-up. Maintaining current levels of combination prevention would lead to increasing HIV incidence and prevalence in South Africa, while the perfect combination scenario was projected to eliminate HIV on a 50-year time scale from 2013 to 2063. Perfecting testing and treatment, without changing condom use or circumcision rates, resulted in an 89% reduction in HIV incidence but not elimination. Universal adult male circumcision alone resulted in a 21% incidence reduction within 20 years. Substantial decreases in HIV incidence are possible from sufficient uptake of both primary prevention and ART, but with continuation of the status quo, HIV elimination in South Africa is unlikely within a 50-year time scale.

Cost-effectiveness of Injectable Preexposure Prophylaxis for HIV Prevention in South Africa.

Long-acting injectable antiretrovirals such as rilpivirine (RPV) could promote adherence to preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention. However, the cost-effectiveness of injectable PrEP is unclear. We constructed a dynamic model of the heterosexual HIV epidemic in KwaZulu-Natal, South Africa, and analyzed scenarios of RPV PrEP scale-up for combination HIV prevention in comparison with a reference scenario without PrEP. We estimated new HIV infections, life-years and costs, and incremental cost-effectiveness ratios (ICERs), over 10-year and lifetime horizons, assuming a societal perspective. Compared with no PrEP, unprioritized scale-up of RVP PrEP covering 2.5%-15% of adults prevented up to 9% of new infections over 10 years. HIV prevention doubled (17%) when the same coverage was prioritized to 20- to 29-year-old women, costing $10 880-$19 213 per infection prevented. Prioritization of PrEP to 80% of individuals at highest behavioral risk achieved comparable prevention (4%-8%) at <1% overall coverage, costing $298-$1242 per infection prevented. Over lifetime, PrEP scale-up among 20- to 29-year-old women was very cost-effective (<$1600 per life-year gained), dominating unprioritized PrEP, while risk prioritization was cost-saving. PrEP's 10-year impact decreased by almost 50% with increases in ICERs (up to 4.2-fold) in conservative base-case analysis. Sensitivity analysis identified PrEP's costs, efficacy, and reliability of delivery as the principal drivers of uncertainty in PrEP's cost-effectiveness, and PrEP remained cost-effective under the assumption of universal access to second-line antiretroviral therapy. Compared with no PrEP, prioritized scale-up of RPV PrEP in KwaZulu-Natal could be very cost-effective or cost-saving, but suboptimal PrEP would erode benefits and increase costs.

Careful Conversations and Careful Sex: HIV Posttesting Experiences Among African American Men in Rural Florida.

In the United States, black/African American (black) men bear the greatest burden of human immunodeficiency virus (HIV), accounting for 42% of new HIV infections in 2012 despite being 6% of the population. In Florida, heterosexual HIV transmission has increased among black men. Few studies have examined HIV testing experiences for black heterosexual men (BHM) in the rural South. This study describes the post-HIV-testing trial experiences of BHM in rural Florida. We conducted 12 focus groups (4-7 participants per group) in 3 rural Florida counties with BHM who participated in a larger randomized HIV testing trial. Interviews were professionally transcribed and data were analyzed using NVivo 10. The qualitative analysis was informed by the strengths perspective (ie, emphasis on abilities rather than risks) and used a thematic analytical approach. Sixty-seven men participated (median age 41.5 years); 39 (58%) earned a monthly income of less than $500, 38 (57%) attained education through high school or higher, 37 (55%) were unmarried, and 40 (60%) reported practicing monogamy; all who tested for HIV were negative for HIV. We identified 3 main themes based on self-reported actions: (1) risk reduction (eg, more consistent condom use, fewer sex partners), (2) sexual health communications with sex partners (eg, negotiating HIV testing with sex partners, getting to know partners better), and (3) health communications with peers and family (eg, disclosing test results, encouraging others to get tested). Among BHM, being in this HIV testing study facilitated increased protective behaviors and communications for HIV prevention. Interventions for BHM in rural areas warrant incorporating these strategies to encourage routine HIV testing.

Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for Adolescents: A Generation at Stake.

Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for Adolescents: A Generation at Stake.

A study of HIV-concordant and -discordant couples attending voluntary counselling and testing services at a tertiary care center in North India.

A large number of Indian couples are exposed to the risk of heterosexual human immunodeficiency virus (HIV) transmission. The present records-based study was undertaken at the voluntary counselling and testing facility of a tertiary care hospital in New Delhi, India to determine HIV prevalence among Indian couples; to assess the magnitude of seroconcordance and discordance among HIV-affected couples; and to compare the concordant and discordant partnerships for sociodemographic determinants and cluster of differentiation 4 (CD4) counts. Of the 1309 couples included in the study, 249 (19%) were HIV-affected, and of them 113 (45.4%) were concordantly and 136 (54.6%) discordantly affected by HIV. Males were the HIV-infected partners in 72% of the serodiscordant partnerships analyzed. Seroconcordance was significantly associated with the occupation status of being a housewife (P = 0.009). The contribution of discordant partnerships to the burden of HIV/acquired immune deficiency syndrome (AIDS) is significant, warranting novel couple-targeted counselling strategies and preventive measures, including safe sexual behavior and possibly preexposure HIV prophylaxis of the uninfected partner.

Conceptualizations of Heterosexual Anal Sex and HIV Risk in Five East African Communities

Heterosexual anal sex is underresearched and little understood, particularly in the African context. Existing prevalence data indicate that heterosexual anal sex is a widespread practice, yet little is known about the way in which it is conceptualized and understood. Describing findings from qualitative research conducted in Kenya, Tanzania, and Uganda, we shed light on conceptualizations of heterosexual anal sex and its relation to human immunodeficiency virus (HIV). These findings suggest that penile-anal sex is practiced by men and women in Africa for a range of reasons, including virginity maintenance, contraception, fulfillment of male pleasure, relationship security, menstruation, in the presence of vaginal complications, financial gain, fidelity, and prestige. Despite anal sex being the most efficient way to transmit HIV sexually, there is widespread lack of knowledge about its risks. These findings describe the ways in which anal sex is conceptualized in five East African communities, highlighting how penile-anal intercourse is often not considered “sex” and how the omission of anal sex in safe-sex messaging is interpreted as meaning that anal sex is safe. In light of its frequency and risks, greater attention must be paid to heterosexual anal sex in Africa to ensure a comprehensive approach to HIV prevention.

Heterosexual HIV in a Creole World but with Western Norms: The Experience of the French Territories of Guadeloupe and Guiana

Besides its geographical locations, the French territories of Guadeloupe and Guiana share a Caribbean and South-American culture but are under French rule of laws and norms. The focus of this paper is to analyze public policies regarding human immunodeficiency virus (HIV) prevention among heterosexuals in this context. An anthropological research was undertaken (2008–2012) in Guadeloupe and Guiana, to explore the construction of gender norms with regards to HIV prevention. It was evidenced that gender role in the Caribbean has multiple paradoxical roots due to colonial history and the creolization of the Caribbean world. Findings suggest interplay and tensions of these socio-historical constructions and sexuality and gender in particular. Through the imposition of Western subjectivity via the control of bodies, gender, and sexualities a “post-colonial bio-power” is revealed to the detriment of a creolized way of life that has taken shape over time in these countries. Improved public policies to address HIV prevention in Guadeloupe and Guiana require the consideration of the socio-historical construction of sexuality and gender in these territories.

Racial/ethnic and gender differences among older adults in nonmonogamous partnerships, time spent single, and human immunodeficiency virus testing.

A higher frequency of nonmonogamy, due in part to lower marriage prevalence, may contribute to elevated human immunodeficiency virus (HIV)/sexually transmitted disease rates among older blacks. To examine race and gender differences in nonmonogamy, time spent single (i.e., not married or cohabiting), and HIV testing in older adults, we analyzed US population-based data from the 2005-2006 National Social Life, Health, and Aging Project for 2825 heterosexual participants ages 57 to 85 years. Blacks spent greater portions of their adult lives single than did Hispanics or whites and were far more likely to report recent nonmonogamous partnerships (23.4% vs. 10.0% and 8.2%). Among individuals reporting sex in the prior 5 years, nonmonogamous partnerships were strongly associated with time spent single during the period. Control for time spent single and other covariates reduced the association of black race with nonmonogamous partnerships for men, but increased it for women. Less than 20% reported ever testing for HIV; less than 6% had been recommended testing by a provider. Testing rates, highest in black men and white women, differed little by history of nonmonogamous partnerships within gender strata. Singlehood helps to explain higher nonmonogamous partnership rates in older black men but not in older black women. Older adults rarely receive or are recommended HIV testing, a key strategy for reducing heterosexual HIV transmission.

The Medical Benefits of Male Circumcision

The Medical Benefits of Male Circumcision

The social context of sexual HIV prevention among female sex workers in China

The recent article on scaling up programmes to prevent sexual human immunodeficiency virus (HIV) transmission is timely and addresses a compelling topic.1 However, there are two points that should be emphasized in understanding how to organize an effective response to China’s expanding sexually transmitted HIV epidemic: (i) the heterogeneity within China’s commercial sex industry; and (ii) the unique organizational and social forces that constrain responses. First, China has >6 million female sex workers (FSWs), based on conservative estimates derived from self-reporting in a population-representative sample.2 Public health and social science research from China suggests that there are distinct typologies of FSW, each with distinct workplaces and sexual risks (Table 1).3 Several studies show that low-income FSWs in China have a higher risk of syphilis and other sexually transmitted infections (STIs), including one systematic review of 72 studies that found a 2-fold increased risk of syphilis among low-income FSWs.4 Yet, there have been few interventions focused on low-income FSWs and methodologically rigorous epidemiological studies are limited. Table 1 Chinese FSW typologies and their workplace and approximate sexual risk Second, some sources have described sex work as ‘illegal’ in China, but this does not appreciate the complex relationship between women who sell sex and local authorities. A common Chinese saying is that police have ‘one eye open and one eye closed’ when considering sex work. Male police and other local authorities have many incentives both to curtail and to permit commercial sex.5 A better understanding of these local relationships informed by epidemiology and social sciences could help illuminate strategies for FSW HIV prevention. Given the remarkable heterogeneity in socio-demographics and sexual risk among FSWs in China, simple policy solutions or importing models from Asian successes should be viewed with caution. Policy solutions for preventing heterosexual HIV that resonate with local FSWs and acknowledge the embedded and highly contextual nature of sexual risk have not been piloted in China and are far from scaling up. More research and programmatic efforts to identify and curb high-risk commercial sex are urgently needed.

Donor and Recipient Envs from Heterosexual Human Immunodeficiency Virus Subtype C Transmission Pairs Require High Receptor Levels for Entry

Compact, glycan-restricted envelope (Env) glycoproteins are selected during heterosexual transmission of subtype C HIV-1. Donor and recipient glycoproteins (Envs) from six transmission pairs were evaluated for entry into HeLa cells expressing different levels of CD4 and CCR5. Donor and recipient Envs demonstrated efficient entry into cells expressing high levels of CD4 and CCR5, and entry declined as CCR5 levels decreased. Infectivity for all Envs was severely impaired in cells expressing low levels of CD4, even at the highest CCR5 levels. In 5/6 pairs, there was no significant difference in efficiency of receptor utilization between the donor and recipient Envs in these HeLa-derived cell lines. Thus, HIV-1 transmission does not appear to select for viruses that can preferentially utilize low levels of entry receptors.

Neisseria gonorrhoeae and Chlamydia trachomatis among human immunodeficiency virus-infected women.

Neisseria gonorrhoeae and Chlamydia trachomatis among human immunodeficiency virus-infected women.

Impact of Mucosal Inflammation on Cervical Human Immunodeficiency Virus (HIV-1)-Specific CD8 T-Cell Responses in the Female Genital Tract during Chronic HIV Infection

The female genital tract is the major route of heterosexual human immunodeficiency virus (HIV) acquisition and transmission. Here, we investigated whether HIV-specific CD8 T-cell-mediated immune responses could be detected in the genital mucosa of chronically HIV-infected women and whether these were associated with either local mucosal HIV shedding or local immune factors. We found that CD8(+) T-cell gamma interferon responses to Gag were detectable at the cervix of HIV-infected women but that the magnitude of genital responses did not correlate with those similarly detected in blood. This indicates that ex vivo HIV responses in one compartment may not be predictive of those in the other. We found that increased genital tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) levels correlated significantly with levels of Gag-specific CD8(+) T cells at the cervix. Women who were detectably shedding virus in the genital tract had significantly increased cervical levels of TNF-alpha, IL-1beta, IL-6, and IL-8 compared to women who were not detectably shedding virus. We were, however, unable to detect any association between the magnitude of cervical HIV-specific responses and mucosal HIV shedding. Our results support the hypothesis that proinflammatory cytokines in the female genital tract may promote HIV replication and shedding. In addition, we further show that inflammatory cytokines are associated with increased levels of HIV-specific CD8 effector cells at the genital mucosa but that these were not able to control genital HIV shedding.