Protocol for the pilot quasi-experimental controlled trial of a gender-responsive implementation strategy with providers to improve HIV outcomes in Uganda.

BACKGROUND: Antiretroviral treatment (ART) is the most effective clinical intervention for reducing morbidity and mortality among persons living with HIV. However, in Uganda, there are disparities between men and women in viral load suppression and related HIV care engagement outcomes, which suggests problems with the implementation of ART. Gender norms are a known driver of HIV disparities in sub-Saharan Africa, and patient-provider relationships are a key factor in HIV care engagement; therefore, the role of gender norms is important to consider in interventions to achieve the equitable provision of treatment and the quality of ART counseling. METHODS: The overall research objective of this study is to pilot test an implementation strategy (i.e., methods to improve the implementation of an evidence-based intervention) to increase providers' capacity to provide gender-responsive treatment and counseling to men and women on HIV treatment in Uganda. Delivered to HIV providers, this group training adapts evidence-based strategies to reduce gender biases and increase skills to deliver gender-specific and transformative HIV counseling to patients. The implementation strategy will be piloted through a quasi-experimental controlled trial. Clinics will be randomly assigned to either the intervention or control conditions. The trial will assess feasibility and acceptability and explore barriers and facilitators to implementation and future adoption while gathering preliminary evidence on the implementation strategy's effectiveness by comparing changes in patient (N = 240) and provider (N = 80-140) outcomes across intervention and control clinics through 12-month follow-up. Quantitative data will be descriptively analyzed, qualitative data will be analyzed through thematic analysis, and these data will be mixed during the presentation and interpretation of results where appropriate. DISCUSSION: This pilot intervention trial will gather preliminary evidence on the acceptability, feasibility, and potential effect of a novel implementation strategy to improve men and women's HIV care engagement, with the potential to reduce gender disparities in HIV outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT05178979 , retrospectively registered on January 5, 2022.

Community-based health workers implementing universal access to HIV testing and treatment: lessons from South Africa and Zambia-HPTN 071 (PopART).

The global expansion of HIV testing, prevention and treatment services is necessary to achieve HIV epidemic control and promote individual and population health benefits for people living with HIV (PLHIV) in sub-Saharan Africa. Community-based health workers (CHWs) could play a key role in supporting implementation at scale. In the HPTN 071 (PopART) trial in Zambia and South Africa, a cadre of 737 study-specific CHWs, working closely with government-employed CHW, were deployed to deliver a 'universal' door-to-door HIV prevention package, including an annual offer of HIV testing and referral services for all households in 14 study communities. We conducted a process evaluation using qualitative and quantitative data collected during the trial (2013-2018) to document the implementation of the CHW intervention in practice. We focused on the recruitment, retention, training and support of CHWs, as they delivered study-specific services. We then used these descriptions to: (i) analyse the fidelity to design of the delivery of the intervention package, and (ii) suggest key insights for the transferability of the intervention to other settings. The data included baseline quantitative data collected with the study-specific CHWs (2014-2018); and qualitative data from key informant interviews with study management (n = 91), observations of CHW training events (n = 12) and annual observations of and group discussions (GD) with intervention staff (n = 68). We show that it was feasible for newly recruited CHWs to implement the PopART intervention with good fidelity, supporting the interpretation of the trial outcome findings. This was despite some challenges in managing service quality and CHW retention in the early years of the programme. We suggest that by prioritizing the adoption of key elements of the in-home HIV services delivery intervention model-including training, emotional support to workers, monitoring and appropriate remuneration for CHWs-these services could be successfully transferred to new settings.

Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand.

OBJECTIVES: To evaluate the prevalence and risk factors of anal squamous intraepithelial lesions (ASIL), the putative anal cancer precursor, in Asian HIV positive and HIV negative men who have sex with men (MSM). METHODS: Men who underwent anal Pap smear reported clinical, sociodemographic and behavioural information collected through questionnaire and interview between January 2007 and April 2008. Chi(2) and logistic regression were used to evaluate ASIL prevalence and risk factors among HIV positive and HIV negative MSM. RESULTS: Of the 174 MSM (mean age 32.1 years), 118 (67.8%) were HIV positive. Overall, 27% had abnormal anal cytology: 13.2% had atypical squamous cells of undetermined significance (ASC-US), 11.5% had low-grade squamous intraepithelial lesion (LSIL) and 2.3% had high-grade squamous intraepithelial lesion (HSIL). Prevalence of ASIL was higher among HIV positive than HIV negative MSM (33.9% vs 12.5%; p = 0.003). Among HIV positive MSM, 16.1% had ASC-US, 14.4% had LSIL and 3.4% had HSIL and 7.1%, 5.4% and 0% in HIV negative MSM, respectively. Anal condyloma was detected in 22% of HIV positive and 16.1% (9/56) of HIV negative MSM (p = 0.5). In HIV positive MSM, anal condyloma (OR 3.42, 95% CI 1.29 to 9.04; p = 0.01) was a significant risk factor for ASIL. Highly active antiretroviral therapy use and CD4+ T cell count were not associated with ASIL. CONCLUSIONS: One-third of HIV positive and 12.5% of HIV negative MSM had ASIL. Thus, as greater numbers of HIV positive MSM live longer due to increasing access to HAART worldwide, effective strategies to screen and manage anal precancerous lesions are needed.

Predictors for casual sex and/or infection among sexually transmitted disease clinic attendees in China.

To assess the risk factors for casual sex and infections among the sexually transmitted disease (STD) clinic attendees in two disparate Chinese cities, an STD clinic-based cross-sectional study was conducted to provide demographic and sexual behaviour information. Participants were recruited from nine STD clinics selected by mapping strategy. STD prevalence was 69.4% (68.6% of men and 65.2% of women). The most common diagnoses were non-gonococcal urethritis (22.2%), genital warts (13.2%), syphilis (11.6%), gonorrhoea (8.4%), chlamydia (6.3%) and herpes simplex virus type 2 (HSV-2) (5.8%). Of 536 participants, 22.5% reported having casual sex in the last three months, younger age, less education, unawareness of transmission routes and having had casual sex in the last three months were independent risk factors for acquisition of an STD. Single or separated marital status, non-local residency and STD diagnoses were independently associated with having had casual sex. After decades of exceedingly low STD rates in China, a full panoply of STD diagnoses are now evident. Both for reproductive health concerns and for stemming the expansion of HIV spread, STD control and prevention must be revitalized as a priority for China's public health and medical institutions. Effective training is a priority, given the dearth of STD-experienced health-care workers.

High-risk behaviours among juvenile prison inmates in Pakistan.

OBJECTIVES: To assess the sexual- and drug-use-related risk behaviours of male juvenile detainees in Karachi, Pakistan. DESIGN: Cross-sectional study. METHODS: A cross-sectional study was conducted of prison inmates aged 15-21 years in Karachi Juvenile Prison in 2002. In total, 321 inmates were interviewed about sexual orientation and behaviours, and knowledge about human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). Urine specimens were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction. RESULTS: A substantial proportion (n=111, 34.6%) of the participants were sexually active. Sixty-two (19%) and 67 (21%) had had sex with a male or female before incarceration, respectively. Twenty-seven (8.4%) participants had an STI, and 50% of the 109 sexually active participants had had multiple sexual partners. Use of addictive substances was associated with sexual activity. The mean knowledge score computed from the sum of 16 items was 4.7, with a median of 2.9. A large proportion (40%) of participants knew about condoms, but very few (3.4%) had ever used one. The mean+/-standard deviation risk score from nine items was 2.4+/-1.7. On the basis of behavioural and biological markers, 117 (36.4%) participants had high-risk behaviour. In multivariate logistic regression analysis, knowledge, risk perception and age were predictive of higher risk. CONCLUSIONS: HIV risk behaviours are common among adolescent inmates. Although inmates do have knowledge about modes of transmission and condom use, the use of condoms is significantly low. Interventions are needed for behavioural change among this group.

Syndromic management training for non-formal care providers in Pakistan improves quality of care for sexually transmitted diseases STD care: a randomized clinical trial.

We conducted a randomized, controlled, three-armed trial to assess whether training in syndromic management, with provision of packets, could improve the quality of STD services provided among non-formal care providers. The quality of STD case management service, observed by "incognito patients" in both intervention groups, improved substantially compared to the control group (p < 0.05). The training-and-packets group performed better in service delivery, HIV-testing referral, and condom provision when compared to the training-only group (all p < 0.05). The training-and-packets group also retained more knowledge and practiced more skillfully at six months post-intervention when compared to the training-only group (p < 0.05). Exit interviews of clients suggested that 81% of providers in the intervention groups offered advice on condom use when compared to none of those in the control group (p < 0.001). Syndromic management training and free syndrome packets for non-formal providers had a positive impact on the quality of STD care among the trained providers.

HIV-infected workers deported from the Gulf States: impact on Southern Pakistan.

HIV prevalence is still very low in Pakistan, but its south Asian location and subgroups with recognized lifestyle risk factors suggest that Pakistan will experience expanded diffusion of HIV. We report the frequency of HIV infections identified by the AIDS Control Programme in the Sindh province of Pakistan. Most HIV positive cases currently reported to the Sindh AIDS Control Programme are found among Pakistani workers deported from the Gulf States and among foreigners. The 58 returned workers with HIV represent 61 to 86% of reported cases in any given year during the 1996-1998 period. Five wives of returning workers have been identified with HIV. Expatriate workers in the Gulf States are tested for HIV routinely, unlike other subgroups in Pakistan. Considering the risk of HIV/AIDS due to regular introduction of HIV from returned workers, and the limited awareness surrounding sexual health and HIV/STD transmission issues in Pakistan, intervention programmes targeted at overseas workers need to be implemented to control the expansion of the HIV epidemic in Pakistan (Int J STD AIDS 1999;10:812-14).

Mode of delivery and other maternal factors influence the acquisition of Streptococcus mutans in infants.

S. mutans plays a key role in dental caries. The extent to which perinatal events influence the acquisition of S. mutans is unclear. We hypothesized that several maternal factors, including the mode of delivery, influence the initial acquisition of S. mutans in infants. A prospective cohort study was conducted in 156 mother-infant pairs. The study found that maternal gestational age (p = 0.04), S. mutans level (p = 0.02), caries score (p = 0.02), sexually transmitted disease (STD) infection experience (p = 0.01), and family income (p = 0.03) had significant effects on the acquisition of S. mutans. Among infants who became infected, those delivered by Caesarean section acquired S. mutans 11.7 mos earlier than did vaginally delivered infants (p = 0.038). C-section infants harbored a single genotype of S. mutans that was identical to that of their mothers (100% fidelity). Analysis of the data demonstrated the possible perinatal influences on infants' acquisition of a member of the cariogenic microbiota, and its potential effect on caries outcome.

Peripheral blood mononuclear cell markers in antiretroviral therapy-naive HIV-infected and high risk seronegative adolescents. Adolescent Medicine HIV/AIDS Research Network.

OBJECTIVE: To examine potential hematologic and immunologic markers for healthy adolescents and for adolescents infected with HIV. DESIGN: The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network (AMHARN) recruits HIV-infected and high-risk HIV-uninfected adolescents, aged at least 13 but less than 19 years. The study evaluates biomedical and behavioral features of HIV infection as observed while under medical care for HIV infection and adolescent health. METHODS: Blood samples were collected from HIV-infected and HIV-uninfected subjects at 16 clinical sites. Cell phenotypes were determined using standard single, dual or three-color flow cytometry. RESULTS: This report includes data at enrollment for 94 HIV-positive adolescents who had never received antiretroviral therapy (ART) (mean age, 17.4 +/- 1.0 years for males and 16.5 +/- 1.3 years for females) and 149 HIV-negative adolescents (mean age, 16.7 +/- 1.2 years for males and 16.6 +/- 1.2 years for females); this is the antiretroviral therapy-naive subset drawn from 294 HIV-positive and 149 HIV-negative adolescents enrolled in the REACH Cohort. The total leukocyte count was significantly reduced in the HIV-positive females in comparison with the HIV-negative females (P < 0.001). There was a reduction in natural killer cells (P < 0.05) in HIV-positive females (mean, 140.6 +/- 104.2 x 10(6) cells/l) in comparison with HIV-negative females (184.3 +/- 142.5 x 10(6) cells/l), whereas no differences were found between the two groups of males. The reduction in the total CD4 cell count in HIV-positive males and females in comparison with the HIV-negative subjects was the consequence of a decrease in both the naive CD4 and memory CD4 components. There was a striking increase in the mean number of CD8 memory cells in HIV-positive compared with HIV-negative adolescents, and a corresponding increase in the percentage of these cells. In contrast, naive CD8 cells were present in increased numbers but their percentage was decreased. CONCLUSIONS: These studies of adolescents provide normative data for high-risk healthy adolescents as well as baseline immunologic data for a cohort of ART-naive HIV-positive adolescents. This comparison suggests that this untreated, recently infected group had relatively intact immunologic parameters.

Rising HIV-1 prevalence among sexually transmitted disease clinic attenders in Jamaica: traumatic sex and genital ulcers as risk factors.

Between November 1990 and January 1991, status of human immunodeficiency virus (HIV) infection was assessed for 522 men and 484 women attending the Comprehensive Health Centre in Kingston, Jamaica, for a new sexually transmitted disease (STD) complaint. Prevalence of HIV type 1 (HIV-1) infection was 3.1% (31 of 1,006), a tenfold rise in seroprevalence in 4.5 years. Nineteen of 517 (3.7%) heterosexual men, 3 of 5 (60%) homosexual/bisexual men, and 9 of 484 (1.9%) women were infected with HIV. In heterosexual men, factors associated with HIV infection after age adjustment included present complaint of genital ulcer [odds ratio (OR) 7.3; 95% confidence interval (CI) 1.4-72], past history of genital ulcer (OR, 4.3; CI, 1.4-12), positive MHATP syphilis serology (OR, 3.4; CI, 1.1-10), sex with a prostitute in the past month (OR, 3.8; CI, 1.1-11). Three or more sex partners in the month prior to complaint (OR, 3.6; CI, 1.0-12), and bruising during sex (OR, 4.0; CI, 1.4-13). On multiple logistic regression analysis, independent associations with HIV infection were shown for bruising during sex (OR, 3.0; CI, 1.1-8.3), positive MHATP syphilis serology (OR, 3.2; CI, 1.1-9.5), and history of genital ulcer (OR, 2.9; CI, 1.0-8.0).(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS heterosexual predominance in the Dominican Republic.

AIDS surveillance data from the Dominican Republic are described for 1983-89. A positive serologic test for HIV was required, and standard clinical criteria were used for defining AIDS. There were 1,202 AIDS cases (820 men, 372 women, 10 of unknown gender) reported to the Ministry of Health, for a cumulative case rate of 17 per 100,000 persons. Rapid growth of the epidemic is noted, with 43% of the total cases reported in 1989. Heterosexual exposure accounts for 53% (593) of all cases, with a male-to-female ratio of 2.2:1, resembling a World Health Organization Pattern I/II country. Prevalence is highest in and surrounding the urbanized tourist areas of Santo Domingo and Puerto Plata and in districts with a high concentration of sugar plantation barracks, where laborers from Haiti and the Dominican Republic work and live. The distribution of AIDS cases is described by transmission exposure category, age, sex, year of diagnosis, and district. The National AIDS Surveillance Program can be improved by validation of exposure transmission categories through selected case investigation and by better reporting through training of health care providers. Surveillance data will assist in targeting future public health efforts to regions and persons at highest risk.

AIDS mortality among Puerto Ricans and other Hispanics in New York City, 1981-1987.

Analysis of AIDS mortality data for New York City for 1981-1987 reveals that Puerto Ricans represent the racial/ethnic group most severely affected by this city's AIDS epidemic. Cumulative age-adjusted AIDS mortality rates among Puerto Rico-born males are significantly higher (362 per 100,000) than among blacks (267), whites (182), or other Hispanic (217) males, and cumulative age-specific mortality rates for males are highest for the Puerto Rico-born in every adult age group. AIDS proportional mortality analysis indicates that in 1987 the proportion of all deaths due to AIDS was 10% among those Puerto Rican-born, 12% among other Hispanics (which includes at least 50% United States-born Puerto Ricans), 6% among blacks, and 2% among whites.

Zidovudine use in AIDS-free HIV-1-seropositive homosexual men in the Multicenter AIDS Cohort Study (MACS), 1987-1989.

Zidovudine use data were examined in the Multicenter AIDS Cohort Study to determine (i) if the proportion of pre-AIDS participants (i.e., CD4+ cells less than 200/mm3 or AIDS-related complex) taking zidovudine is high enough to explain a slower than expected rise in AIDS incidence in U.S. homosexual men since mid-1987; (ii) which factors are associated with starting zidovudine and clinical trials of zidovudine; and (iii) if pre-AIDS patients, as a group, are being undertreated. Data on zidovudine use, clinical trial participation, and sociodemographic, clinical, and hematologic variables were collected every 6 months from 1,195 AIDS-free HIV-1-seropositive homosexual men from April 1987 to September 1989. Overall prevalence of zidovudine use rose from 3.6% in mid-1987 (visit 7) to 23% in mid-1989 (visit 11). Of those with less than 200 CD4+ lymphocytes/mm3, the prevalence of zidovudine use rose from 23% (24% if those taking zidovudine or placebo as part of a clinical trial are included) at visit 7 to 58% (69%) at visit 11. Of those with ARC, 20% (23%) were using zidovudine at visit 7 and 55% (65%) at visit 11. Although numbers were small, the advanced ARC participants (CD4+ cells less than 200/mm3 and two or more symptoms) reported the highest treatment rates (50, 78, 80, 60, and 74% at visits 7-11, respectively). By September 1989, 42% (31%) of those with CD4+ lymphocyte levels less than 200/mm3 were still not receiving zidovudine, suggesting that many high-risk, pre-AIDS individuals are being undertreated. To explore this finding further, we examined a range of sociodemographic, hematologic, and clinical variables to determine which factors best predicted initiation of zidovudine therapy outside of clinical trials. In multivariate analyses, CD4+ lymphocyte number was the most consistent predictor of initiation of therapy over all four study visits. For each 100 cells/mm3 deficit, the odds ratios were 2.3 (95% C.I. of 1.7-3.1) at visit 7 and 1.7% (95% C.I. of 1.4-2.0) at visit 11. Symptom status and education level were also associated with starting zidovudine, but not at all visits. The relatively low predictive power of the clinical variables raises and the possibility that nonclinical factors not measured in the MACS (drug cost, third-party insurance restrictions, and individual preferences) may play an important role in predicting zidovudine use. Finally, comparisons were made between seropositive participants starting clinical trials of zidovudine and the rest of the study population. No important differences were found in demographic or major clinical variables between clinical trial participants and zidovudine nonusers in this study.

Cervical cytologic abnormalities and papillomavirus in women infected with human immunodeficiency virus.

We investigated the relationship of human papillomavirus (HPV) infection of the female genital tract, cervical cytology, and human immunodeficiency virus (HIV) infection in 67 women. Forty-eight women had a history of intravenous drug use, 18 were heterosexual partners of HIV-infected intravenous drug users, and one was a transfusion recipient. Patients received a Pap smear, cervicovaginal lavage for HPV determination by Southern blot, HIV serum antibody by enzyme immunoassay with Western blot confirmation, and thorough screening for other sexually transmitted diseases. Seventeen of the 35 (49%) women seropositive for HIV had HPV infection, compared with 8 of 32 (25%) seronegative women (p less than 0.05). Fourteen of 35 (40%) HIV-positive women had squamous intraepithelial lesions (SIL) on cervical cytology, compared with three of 32 (9%) HIV-negative women (p less than 0.01). Of 22 women with symptomatic HIV infection, 11 (50%) had SIL on cytology; 10 of these 11 were HPV-positive. Among 13 asymptomatic HIV-positive women, only three (23%) had such cytological lesions. Our findings strongly suggest that HIV-induced immunosuppression exacerbates HPV-mediated cervical cytologic abnormalities.

National AIDS incidence trends and the extent of zidovudine therapy in selected demographic and transmission groups.

After mid-1987 fewer than the expected number of cases of AIDS were reported in the United States in some demographic and transmission groups but not in others. Gay men (regardless of intravenous drug use), adults with hemophilia, and transfusion recipients exhibited fewer cases than expected based on previously reliable models. These favorable trends could not be explained by assuming earlier cessation of human immunodeficiency virus (HIV) infection. Favorable AIDS incidence trends were not found in heterosexual intravenous drug users or in persons infected through heterosexual contact. White gay men from New York City, Los Angeles, and San Francisco experienced markedly favorable trends, whereas little changes was observed for nonwhite gay men from nonurban areas. AIDS incidence trends were quantitatively consistent with the fraction of AIDS-free persons with severe immunodeficiency who received zidovudine in three cohorts. Gay men in San Francisco used zidovudine more frequently than did adults with hemophilia, while little was used by intravenous drug users in New York City. Data describing the initial national distribution of zidovudine (March 31-September 18, 1987) indicated relatively high use by patients with severe immunodeficiency in those groups, such as urban white gay men, that subsequently experienced fewer cases of AIDS than expected. Available data suggest that zidovudine, perhaps in combination with other therapies, has been one factor contributing to favorable AIDS incidence trends in some groups. Broader application of therapy might further retard the incidence of AIDS, especially in intravenous drug users, persons infected through heterosexual contact, minorities, women, and persons diagnosed outside major metropolitan areas.

Gonorrhea and syphilis in incarcerated urban adolescents: prevalence and physical signs.

During a 1-year period from July 1983 to June 1984, 285 adolescent girls and 2,236 adolescent boys, ranging in age from 9 to 18 years (89% were 14 to 16 years of age), were screened for gonorrhea and syphilis on entry into a detention facility in New York City. The prevalence rate for gonorrhea was 3% for boys and 18.3% for girls, and the prevalence rate for syphilis was 0.63% for boys and 2.5% for girls. The rates of gonorrhea without penile or cervical discharge on physical examination were 2.1% for boys and 10.9% for girls. This high prevalence of syphilis and gonorrhea and the high frequency of disease without physical signs of illness indicate the desirability of screening high-risk adolescents for these and other sexually transmitted diseases. Our data support the need for programs in detention facilities and, we believe, schools, to encourage use of barrier contraceptives to control gonorrhea, syphilis, Chlamydia, human papillomavirus, human immunodeficiency virus, and unwanted pregnancy.

Needle injuries among pediatric housestaff physicians in New York City.

Concerns regarding accidental needle puncture wounds, needle injuries among house officers have increased following reports of human immunodeficiency virus (HIV) transmission via this route. Pediatric house officers training in areas with large numbers of children infected with HIV may face a significant risk of occupational HIV infection via needle injury. The cumulative incidence of needle injury among pediatric house officers in New York who completed at least 1 year of training was ascertained. A questionnaire designed to elicit retrospective information regarding needle injuries was completed by 294 house officers in medical school-affiliated pediatric training programs. A total of 205 (69.7%) had stuck themselves or been stuck with a needle contaminated with a patient's blood, and 48 (17%) reported a needle injury involving a needle contaminated with the blood of a patient with suspected HIV infection. Only 11 of the 48 had received counselling or HIV testing following their possible HIV exposure. These data indicate that needle injury among pediatric house officers in New York is common. Reducing occupational risk is an especially compelling policy issue for pediatric training programs in areas where HIV is endemic.

The role of prevention research in HIV vaccine trials.

The National Institute of Allergy and Infectious Diseases has prepared for HIV vaccine efficacy trials with the hope of having a product which is deemed worthy of testing. This has entailed development of new field research infrastructure and training, in collaboration with many partners. Notably, experts in observational research and experts in field HIV prevention research have joined together in efforts to share their mutually reinforcing experiences. In crafting these potential trial sites, it has become evident that the same criteria that apply in vaccine site suitability should also apply to other prevention clinical trials. These criteria include novel approaches to barriers to sexual transmission, including topical microbicides/spermicides, treatment of sexually transmitted infections, reduction in intrapartum blood contamination, and various strategies to ensure clean needle use. Like vaccines, most of these interventions are theoretically plausible, but remain untested. With or without large scale vaccine trials, these other prevention technologies remain high priorities for HIV research.

Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa.

More than 80% of the world's HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of female-to-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or = 100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.

How can epidemiology assist in guiding interventions for the acquired immunodeficiency syndrome/human immunodeficiency virus?

In a single decade, the pandemic of human immunodeficiency virus (HIV) infection has become an international health, social, and economic emergency. Early and effective intervention is urgently needed for both prevention of HIV infection and for the amelioration of clinical disease. Results of therapeutic trials have suggested expanding the population for which chemotherapy is indicated. In this paper, we first review the findings from selected recent drug trials, using zidovudine and pentamidine as examples. We then discuss six issues that we believe to be crucial for future epidemiologic research in the service of vaccine and drug development: 1. To identify which complications of HIV infection most urgently require development of new therapies, we must characterize the frequency and severity of specific medical events (outcomes) in persons taking a variety of treatments. 2. Currently, acquired immunodeficiency syndrome (AIDS) therapeutic trials gauge the effectiveness of new therapies by their impact on such clinical parameters as the time to development of AIDS or death. These approaches take too long to provide information. We urgently need to identify surrogate markers of clinical outcome that will be useful in the early assessment of treatment efficacy. 3. Progress in vaccine development is being retarded because we do not have enough data from natural history studies on host immunologic responses to suggest that a given response is protective. We therefore need to identify natural correlates of immunity, which can help set priorities in vaccine development. 4. Discovery that a therapy works in the setting of a clinical trial is only a first step in intervention. We must also assess the impact of new therapies on the health of the public, evaluating access to health care, compliance, and other barriers to treatment. 5. Clinical trials are usually associated with the effort to prevent disease in infected persons. However, other trials are needed to assess efforts to interrupt viral transmission through use of condoms, use of virucides, and treatment of sexually transmitted diseases, and by effecting specific behavioral changes. 6. Traditional methods of conducting clinical therapeutic research may not be adequate to address urgent questions in the AIDS/HIV epidemic. We must develop innovative clinical research methods, including better use of data from observational studies, to infer what we can about the effect of treatment on the clinical course.